Cyclophosphamide (CTX) is a chemotherapeutic agent with cytotoxic and immunosuppressive activity. It is used to treat a wide variety of cancers and autoimmune diseases. However, side effects caused by its toxic metabolites, especially hepatotoxicity, limit its clinical application. The natural dihydroflavonol compound dihydromyricetin (DHM) has anticancer, anti-inflammatory, and antioxidant properties. This study aimed to evaluate the protective effects of DHM against CTX-induced hepatotoxicity in mice. Male ICR mice were pretreated with DHM (100, 200, and 400mg/kg b.w.) orally before intraperitoneal injection with CTX (100mg/kg b.w.) for 7 days. The mice were then sacrificed to analyze biochemical and histological parameters as well as metabolomics profiles. DHM ameliorated CTX-induced elevations in the liver index, alanine aminotransferase, aspartate transaminase, and malondialdehyde levels, and pathological changes and increased levels of glutathione and antioxidant enzymes, such as superoxide dismutase and catalase. Based on a KEGG pathway analysis of altered serum and liver metabolites, OXPHOS may play an important role in the observed protective effects. Further analysis revealed that DHM increased the activity of Na⁺-K⁺-ATPase in mice, which affected CTX-induced mitochondrial energy metabolism. To conclude, DHM protected against CTX-induced hepatotoxicity, possibly through reducing oxidative stress and regulating energy metabolism, providing a potential strategy for treatment and prevention.

Molecular recognition and detection are the main concerns in the field of biological analysis because they can be affected by various factors. Single-walled carbon nanotube (SWCNTs)-based optical biosensors have been applied in this field owing to their high sensitivity, good fluorescence stability, and tissue transparency. Purification of single-chiral SWCNTs and surface functionalization of SWCNTs are effective strategies for achieving real-time monitoring and high-throughput screening of biological analytes. Combining these technologies with microfluidic platforms and machine learning algorithms further broadens the application areas of sensors and enhances their analytical performance and usefulness in complex biological systems. Therefore, this review first discusses the preparation methods for single-chiral SWCNTs in recent years and introduces covalent and non-covalent functionalization techniques for SWCNTs, including oligonucleotide chains, peptides, and surfactant modifications. Subsequently, we systematically evaluate the applications of functionalized SWCNT biosensors for recognizing small molecules, including gas phase composition, neurotransmitters, and reactive oxygen species. These biosensors have been shown to have high sensitivity and specificity in the detection of a wide range of small molecules, offering a wide range of possibilities for analyzing volatile organic compounds, signaling molecules, and reactive oxygen species within biological systems, and providing new ways of gaining insights into the complex mechanisms of disease progression. Finally, we have analyzed the ability of SWCNT biosensors to recognize biomolecules in various categories, including proteins, nucleic acids, and lipids. Using these sensors for clinical disease diagnosis improves the accuracy and timeliness of diagnosis and opens up new ways to improve patients' prognosis and quality of life. We believe that SWCNT biosensors have great potential for future development in biomedicine.

Garcioligantone J and K (GLJ and GLK) are a pair of isomers isolated from Garcinia Oligantha Merr. Herein, we described the structure elucidation including the absolute configurations of GLJ and GLK, explored and compared their anti-cancerous effects and underlying mechanism in A549 and NCI-H292 cells. The results indicated that GLJ and GLK are two isomers with different configuration at C-12, they inhibited cell proliferation and induced apoptosis in two lung cancer cell lines with almost the same extent. The induction of apoptosis by GLJ and GLK was demonstrated by DAPI and annexin-V-FITC/PI staining. Further investigation revealed increased Bax/Bcl-2 ratio, cleaved caspase-3, caspase-9 and PARP, loss of mitochondrial membrane potential (MMP) in cells, indicating that GLJ and GLK induced mitochondrial apoptosis. Increased GRP78, p-eIF2 α and GADD153 manifested that endoplasmic reticulum (ER) stress was induced by GLJ and GLK. Meanwhile, upregulated reactive oxygen species (ROS) level was found and GLJ and GLK-induced ER stress and apoptosis could be attenuated by ROS scavenger NAC. Apoptosis induced by GLJ and GLK also could be alleviated by ER stress inhibitor 4-PBA. These showed that GLJ and GLK-induced apoptosis was mediated by ER stress relied on ROS generation. The efficacy of GLJ and GLK on lung cancer cell proliferation was further demonstrated in a zebrafish xenograft model. Collectively, the absolute configurations of GLJ and GLK were identified and they exerted lethal effects on lung cancer cells to the same extent via ROS-ER stress-mitochondrial apoptosis signaling, suggesting that GLJ and GLK might be used as potential modulating agents in lung cancer treatments.

Tadalafil (TD) is a phosphodiesterase type 5 (PDE-5) inhibitor that has gained attention for its wound healing properties. In this study, a TD-loaded hydrogel was prepared and characterized, and its wound-healing efficacy was evaluated. After preparing the TD hydrogel, its physicochemical properties such as viscosity, pH, drugloading capacity (DL%), in vitro release behavior, and stability were characterized. Moreover, in vivo studies were performed to evaluate hydroxyproline (HP) and the wound healing efficacy of 1,1.5,3\%(w/w) TD hydrogels in New Zealand rabbits. Histopathological analysis was also performed using hematoxylin and eosin (H&E) staining. We successfully prepared a TD hydrogel with high stability. The results of the in vivo experiments on full-thickness wounds showed that the 1.5%TD hydrogel with a pH of 5.81±0.421, viscosity of 12,435±63, drug-loading capacity of 91.73±1.482%, and drug release rate of 88% was superior to other formulations when HP level was increased, which decreased the time required for wound healing; this was corroborated by the histological analysis. Thus, the TD hydrogel formulation prepared in this study is a promising topical therapeutic agent for wound healing.

Lutein (LT) is an attractive nutrient for eye health, although it has low water solubility and poor oral absorption. The present study aimed to develop a novel nanodispersion (ND) of LT using a metastable polymorph, offering improved oral absorption of LT. A metastable crystalline form of LT (LT-II) and hydroxypropyl cellulose were subjected to wet-milling followed by freeze-drying to obtain the ND of LT-II (ND/LT-II), and its physicochemical, photochemical, and pharmacokinetic properties of LT samples were evaluated. The mean particle size of LT-II in ND/LT-II was 354 nm, and there was no significant change in the crystalline form of LT-II, even after wet milling and freeze-drying. LT generated significant amounts of superoxide anions upon exposure to pseudo-sunlight (250W/m²), indicating high photoreactivity. After irradiation with pseudo-sunlight (250 W/m²,30 min), the percentages of LT remaining in the LT solution, amorphous LT, and ND/LT-II were 75, 79, and 92%, respectively. LTII dissolved slightly faster than the stable crystalline form of LT (LT-I) in the dissolution media. ND/LT-II further improved the dissolution property of LT-II, and the dissolved amount of LT was 137- and 7.2-fold higher than that of LT-I and LT-II, respectively, at 2 h after dispersion in water. After administration of LT samples (100 mg -LT/kg), systemic exposure to LT in the LT-I and LT-II was negligible, whereas a marked improvement in oral absorption was observed in the ND/LT-II groups. Thus, applying ND technology to LT-II may improve oral absorption, and thus the nutrient function of LT.

Antidepressant mirtazapine (MRZ) has been drawing attention in the management of delirium. However, oral use of MRZ could have drawbacks in onset of actions and ease of administration by caregivers. This study was the first attempt to develop nasal powder formulation (NP), an easily-administered formulation, of MRZ containing a microenvironmental pH -modifier for rapid dissolution and absorption. Ten mixtures of MRZ and counterions were tested in terms of the supersaturation level and stability to select a favorable pH-modifier. NP of MRZ (NP/MRZ) with the selected counterion was prepared by jet milling and characterized regarding physicochemical properties and pharmacokinetic (PK) behaviors after intranasal administration to rabbits. In phosphate buffer solution (PBS, pH5.6), glutamic acid (Glu) showed 10.7 -fold supersaturation of MRZ, with the value being the highest among the ten counterions tested. The addition of Glu led to no significant change in the photostability or chemical stability of MRZ compared with crystalline MRZ. NP/MRZ with Glu (NP/MRZ-E) consisted of microcrystals of MRZ and Glu attached to lactose carriers, and over 93% of MRZ was emitted from a capsule in Jetlizer^TM. Both NP/MRZ-E and NP/MRZ exhibited enhanced dissolution in PBS compared with crystalline MRZ, and more rapid dissolution was observed for NP/MRZ-E. In rabbits, a crushed MRZ tablet (3mg-MRZ/kg, p.o.) exhibited a time to maximum plasma concentration (T_max) and bioavailability (BA) of 72 min and 10%, respectively. NP/MRZ-E (0.3 mg -MRZ/ kg, i.n.) showed T_max  of <5 min with BA of 93%, and this result might be due to rapid dissolution/permeation in nasal mucosa and avoidance of the hepatic first-pass effect. In conclusion, NP employing a microenvironmental pH -modifier would be a promising dosage form of MRZ to offer rapid nasal absorption.

This study explores microdynamic flowability as an innovative approach for early active pharmaceutical ingredient (API) characterisation, when compounds are often scarce and/or expensive. By incorporating small-scale flow measurements during the pre-formulation stage, we aim to support strategic decision-making in formulation development and process design. Laboratory-scale micronisation of the poorly water-soluble drug Palbociclib, while enhancing dissolution, was found to adversely affect flowability. Agglomeration driven by cohesive forces was quantitatively described for the first time via image analysis using sample quantities of less than 200 mg. Our findings demonstrate that microdynamic flow studies provide critical insights into the processability of APIs under low-stress conditions, such as those relevant to research and development (R&D) tablet presses. These results highlight the value of advanced flowability analysis in early-stage development, enabling improved understanding and control of powder processing in pharmaceutical manufacturing and particle engineering.

Paracetamol (PMCL) is an analgesic-antipyretic drug. It is frequently used as an over-the-counter (OTC) drug in many countries around the world, especially for headaches, mild pain, and fever. Knowing its toxic effects on the nervous and hepatic systems, it has been combined with the psychoactive drug caffeine. However, PMCL's antipyretic action during fevers caused by various pathogens might be due to its antimicrobial power. Therefore, we have a question about whether PMCL can be used as an OTC medication or not. This review aimed to summarize the antimicrobial activity, facts behind it, possible action mechanisms, and causes of resistance growth, along with the antimicrobial and toxicological impacts of its metabolites, derived products, and combination products, on the basis of database reports. Numerous pieces of evidence suggest that both PMCL and caffeine have broad-spectrum antimicrobial effects. PMCL is evidently effective against gram-positive and gram-negative bacteria, fungi, viruses, and protozoa. Its major toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI), also has antimicrobial potential. Despite its antimicrobial effects, PMCL has contributed to antimicrobial resistance. In conclusion, according to the findings from database reports, PMCL is not only an analgesic-antipyretic drug, but it also has broad-spectrum antimicrobial potential against many pathogenic gram-positive and gram-negative bacteria and fungi as well as some viruses and protozoa. The use of PMCL as an OTC medication might bring a dangerous health issue in the future among the population, for example, growing microbial resistance and harmful toxicological impacts in different organs in humans.

Glutarimide-containing polyketides (GPs) are an important class of natural products with antifungal, antibacterial, antitumor and other biological activities. Generally, the structures have a six-membered ring of glutarimide (also known as 2,6-piperidinedione) and a polyketide side chain or a ring of varying lengths attached at C 4 such as cycloheximide, 9-methylstreptimidone and migrastatin. Currently, at least 65 natural glutarimide antibiotics have been isolated and identified. The novel biosynthetic mechanism of the trans-AT PKS and multifaceted modes of action have promoted the progressive exploration of glutarimide-containing products. However, the related information on the aspects of new structure discovery, biological activity and biosynthesis of GPs is still not available. This review summarizes the current research from the aspects of new structure discovery, biological activity and biosynthesis, aiming to provide a reference for in-depth products mining and structure-activity relationship research. Special emphasis is placed on their potential as drug leads, particularly in cancer therapy, and the role of modern analytical techniques in their discovery and characterization.

Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancer with high mortality and limited therapeutic strategy. Glycine decarboxylase (GLDC) is the key limiting enzyme in glycine breakdown metabolism and acts as oncogene or tumor suppressor to impact tumor onset and progression in a context dependent manner. However, the underlying mechanism of GLDC on autophagy and progression is largely unexplored in HCC. Here, we showed that GLDC overexpression inhibited cell proliferation, cell migration and promoted cell senescence and autophagy in HCC. Intriguingly, induced GLDC remarkably attenuated epithelial-mesenchymal transition (EMT) progress and tumor growth in vitro and in vivo. Mechanically, we demonstrated that GLDC upregulated VPS34 protein and enhanced its interaction with VPS34, thus promoting the association of VPS34 with Beclin1/ ATG14 complex and autophagy induction in HCC. Importantly, GLDC acetylation at K514 promoted interaction of GLDC-VPS34, whereas GLDC acetylation-dead mutant K514R abolished their binding. Furthermore, GLDC protein was decreased in HCC tissues compared with para-tumor tissues and reduced GLDC was significantly correlated with poor prognosis of patients. In conclusion, we unveil the key regulatory role of GLDC in autophagy and HCC progression through VPS34 and provide a potential strategy for HCC therapy.

Naturally occurring substance, D-pinitol (DPL) belongs to the significant inositol family has numerous pharmacological activity. In this study we evaluated the anti-emetic effect as well as modulation activities of DPL on the recent market drugs aprepitant (APR), domperidone (DOM), hyoscine butyl bromide (HYS), and ondansetron (ODN) on emesis in the chick model. To highlight the possible anti-emetic activity in copper sulfate induced emesis chick models, we use several reference drugs, such as APR (26mg/kg), DOM (7mg/kg), OND (5mg/kg), and HYS (21mg/kg), as positive controls, while the vehicles serve as negative controls. All reference drugs are given alone or in combined groups to evaluate their anti-emetic and modulation effects. The results suggest DPL (25 or 50mg/kg) increases the mean number of latency in the chicks compared to vehicles, and the combination groups, DPL (25mg/kg) showed better anti-emetic effects with DOM and ODN while DPL (50mg/kg) reduces the number of retches compared to vehicles and combined drug therapy with reference drugs. Additionally, A variety of computational algorithms were used to visualise ligand-receptor interactions and quantify the binding affinities of DPL and other ligands towards the dopamine receptors (D2 and D3), muscarinic acetylcholine receptors (M1-M5), and serotonin receptor (5HT3). The molecular docking study indicated that DPL exhibits the highest binding affinity towards subtypes M2 (having a docking score of -5.7kcal/mol) and D3 (having a docking score of -5.7kcal/mol) in comparison to certain standards for these receptors, which have docking scores of DOM (-9.7kcal/mol) and HYS (-7.1kcal/mol) for M2 and D3, respectively. Our findings suggest that DPL has antiemetic properties in chicks, possibly through interactions with the M2 and D3 receptor pathways.

Osteopontin (OPN), also known as secreted phosphoprotein 1(SPP1), is a highly glycosylated and phosphorylated acidic protein, which is a multifunctional glycoprotein expressed in numerous cell types. SPP1 is involved in the attachment of osteoclasts to mineralized bone matrix, inflammatory reaction, cell recruitment, and tissue repair, and plays an important role in bone formation, fibrosis, immune diseases, and cancer. The role of SPP1 in osteoporosis, osteoarthritis and cancer is multi-faceted. While it holds potential therapeutic value, it also presents certain limitations. This review integrates the molecular structural characteristics of SPP1, including isoform variants and post-translational modifications, with its pathophysiological functions. It highlights the regulatory roles of SPP1 in these diseases: maintaining the dynamic balance between bone resorption and formation in osteoporosis, promoting cartilage degeneration and inflammation in osteoarthritis, and driving tumor progression in cancer through the activation of pathways such as PI3K/AKT/mTOR. Furthermore, SPP1 regulates tumorassociated macrophages and fibroblasts within the tumor microenvironment, thereby facilitating immune evasion and metastasis. The article also underscores the potential value of precisely modulating SPP1 activity in the treatment of osteoporosis and osteoarthritis and suggests a combined therapeutic strategy targeting SPP1, offering novel insights into overcoming the limitations of single-target cancer therapies.

Temozolomide (TMZ) is the first-line chemotherapeutic agent for treating glioblastoma multiforme (GBM), but its potency is hampered by inevitable drug resistance and systematic toxicity. Novel strategies that can decrease drug-associated adverse events are urgently needed. Encouraged by the significant pro-apoptotic, anti-inflammatory, and anti-proliferative properties of resveratrol (RES), one of the most widely studied polyphenolic compounds in cancer therapy, we propose a synergistic therapeutic strategy by using the combination of TMZ and RES to inhibit GBM progression. Recently, exosomes (Exos) have received increasing attention as promising drug delivery alternatives with favorable intrinsic features. In this work, Exos derived from homologous U87 cells are developed to co-deliver TMZ/RES for GBM therapy, defined as U87-Exos@TMZ/RES. It is found that U87-Exos@TMZ/RES share various advantages, including intrinsic tumor-targeting accumulation with homologous effects, as well as enhanced antitumor activity with synergistic effects of TMZ and RES. Furthermore, the excellent therapeutic effect of U87-Exos@TMZ/RES is also achieved in orthotopic GBM models. Based on these results, this novel U87-Exos@TMZ/RES delivery platform can provide a promising systemic chemotherapy strategy for enhancing GBM treatment.

The coronavirus disease-2019 (COVID-19) pandemic, etiologically caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has profoundly impacted the global health. While vaccines have been developed, they have shown limited efficacy in treating patients already under infection or preventing infection with emerging SARS-CoV-2 variants. The nonstructural protein 16 (NSP16), with the assistance of the nonstructural protein 10 (NSP10), is responsible for forming the Cap-1 structure, which is critical for viral replication and immune evasion through the 5^'-capping of viral mRNA. As a result, NSP16/NSP10 has emerged as a promising target for antiviral treatment of coronaviruses. In this study, we aimed to discover small molecule inhibitors of NSP16/NSP10 by leveraging recent structural insights and combined tools of virtual and experimental screenings. We designed a simple scintillation proximity assay to enable biochemical testing for NSP16/NSP10 enzymatic activity and applied it to screen inhibitors from candidate hit compounds that are derived from molecular docking-based virtual screenings. We identified potential hits that inhibit the NSP16 activity with cellular efficacy. Together with structural analysis and chemotype categorization, this study lays the groundwork for novel antiviral therapeutics development against SARS-CoV-2 and related coronaviruses.

The SphK1 inhibitor development is of great importance for the treatment of non-small cell lung cancer (NSCLC). In this study, CHJ01 which has been previously shown anti-tumor effects was introduced to investigate the detailed antitumor mechanism both in vitro and in vivo. CHJ01 inhibited the A549 cell proliferation, migration, and invasion significantly and showed cytotoxicity to A549. CHJ01 induced G0/G1 cell cycle arrest by increasing ceramide levels and altered the expression of TRAF2, Bcl-2, Bax and RELA. CHJ01 inhibited the TRAF2/NF-кB signaling pathway and promoted apoptosis by downregulating Bcl-2 and upregulating Bax. In vivo anti-tumor effects were investigated using a nude mouse ectopic tumor model. CHJ01 reduced the volumes and weights of xenograft tumor in nude mice. CHJ01 induced apoptosis by HE staining and immunohistochemistry assay. These results indicated that CHJ01 can be a potential candidate for the treatment of NSCLC.

Hirudin is an effective active ingredient derived from the salivary glands of leech. It is a small peptide molecule consisting of 65-66 amino acids and demonstrates a strong inhibitory effect on thrombin, providing beneficial anticoagulant and antithrombotic properties. However, as a biopharmaceutical peptide, it has some drawbacks such as easy degradation, short half-life, low bioavailability, and high risk of hemorrhage in clinical use. To overcome these challenges, various formulations were developed. In this work, a comprehensive review of research progress was provided in both traditional and novel hirudin formulations, spanning from lyophilized powders to biotechnology-based pharmaceuticals, covering various dosage forms to offer comprehensive references for field research. Firstly the advantages and limitations of conventional preparations were assessed such as freeze-dried powders, capsules, and injections. Then a detailed exploration of frontier strategies including nanotechnology-based delivery systems, transdermal formulations, and biotechnology-driven prodrug designs were conducted. This article aims to comprehensively analyze cutting-edge advancements in hirudin preparation research, providing updated information for relevant researchers by integrating traditional dosage optimization with breakthrough emerging technologies.

Tenofovir (TNF) is an antiretroviral drug that has being used as a topical microbicide to prevent human immunodeficiency virus transmission (HIV). Cyanovirin-N (CV-N) is a lectin protein that can bind to the HIV envelope glycoprotein and inhibit viral entry. The combination of TNF and CV-N may have synergistic effects and enhance the efficacy of microbicide. The aim of this study was to develop and optimize composite hydrogel formulations containing 1%TNF and 0.0005% CV-N using Box Behnken Design. A three-factor, three-level BoxBehnken design was employed to investigate the effects of the concentrations of PEG₂₀₀₀, sodium carboxyl methylcellulose (NaCMC), and calcium chloride on the release of Tenofovir, flux, and mucoadhesion. The mucoadhesion was evaluated by measuring the percent mucin adsorption while flux and release kinetics were evaluated using the Franz cell diffusion method. The optimal hydrogel formulation was found to contain 4% NaCMC, 2% PEG2000 and 1% CaCl₂. The hydrogel had a pH of 4.5±0.017, a viscosity of 275600±0.65cP, flux 9806μ g/cm²/h for TNF with a drug release of 119, 205.6μ g/cm². The TNF gel exhibited a pseudoplastic rheological behavior with 96.3% muco-adhesion. The study successfully developed an optimized TNF/CV-N mucoadhesive hydrogel, highlighting its potential as an on-demand multipurpose prevention technology (MPT) for HIV. The formulation was optimized to ensure good drug release, flux and mucoadhesion. The optimized hydrogel offers a convenient, effective method for preventing sexually transmitted infections (STIs), addressing critical challenges in drug delivery and user adherence while advancing public health strategies for STIs.

Despite significant advancements in highly active antiretroviral therapy (HAART), Human Immunodeficiency Virus (HIV) remains a global health challenge due to its high mutation rate, drug resistance, and the complexity of treatment optimization. Artificial intelligence (AI) has emerged as a transformative tool in HIV research, offering innovative solutions for predicting viral mutations, optimizing drug discovery and formulation design. However, challenges such as limited access to diverse datasets, ethical concerns, and model interpretability hinder the full potential of AI in HIV research. This review highlights gaps in AI-driven HIV research and explores advancements to address these challenges. AI-driven platforms, such as DeepHIV and geno2pheno, have demonstrated success in forecasting resistance mutations and guiding therapeutic decisions. AI is also revolutionizing drug formulation development by enhancing solubility, bioavailability, and stability, while improving patient adherence through advanced delivery systems. Current applications of AI in HIV mutation prediction, drug discovery, and formulation optimization have highlighted the potential of AI towards HIV management and eradication while addressing gaps in data availability and model transparency. By integrating structural, pharmacological, and clinical data, AI provides a comprehensive framework for rational drug design and personalized treatment strategies. By leveraging AI-driven insights, HIV treatment and prevention can become more personalized, efficient, and sustainable. Future research should focus on overcoming data limitations, enhancing model interpretability, and exploring innovative AI approaches to contribute to the global fight against the HIV epidemic.

Among natural sources of animal origin, the most similar to human in composition is porcine skin. Crushed cryolyophilized xenoderm of porcine skin from 1st layer is used for preparation a dietary supplement Xenoderm in the form of powder, capsules and tablets. Also, an additional natural active pharmaceutical ingredient is 2nd layer from cryolyophilized xenoderm of porcine skin, which was not used before. In this study, composition and technology of combined tablets based on the powders of the 1st and 2nd layers from the cryolyophilized xenoderm of porcine skin were develop and characterized. It was evaluated pharmaco-technological properties of the tableting blend such as bulk density, tapped density, flowability and angle of repose. The tablets were prepared by direct compression method. They were studied for appearance, uniformity of dosage units, hardness, friability and disintegration. The effect of fillers, disintegrants, and glidants on 9 pharmaco-technological properties of the tableting blend and tablets was investigated using dispersion analysis. By desirability function the advantages of Neusilin® US2, calcium dihydrogen phosphate anhydrous and sorbitol, croscarmellose sodium and polyplasdone XL-10 are shown. The quantities of excipients were investigated using method of random balance. The interaction between quantities of excipients and the quality of tableting blend and tablets was proved using method of regression analysis. Optimal combination of croscarmellose sodium, Neusilin® US2, microcrystalline cellulose 102 and magnesium stearate is justified. New combined tablets under the conventional name Combiderm are obtained by direct compression method. Optimal tablet pressing parameters are selected in the range from 290 MPa to 435 MPa. We successfully prepared the tablets with a good consumer appearance and conformity pharmacopoeial requirements. The proposed methodology could be an algorithm for the pharmaceutical development of other combined tablets using statistical methods.

Intestinal ischemia-reperfusion injury (IIRI) is a serious pathological condition that not only causes local damage to the intestine but also contributes to injury in distant organs such as the heart. Basella alba, a commonly consumed leafy vegetable with known antimicrobial, anti-inflammatory, and antioxidant properties in traditional medicine, is believed to have protective effects against such injuries. This study aimed to investigate the cardioprotective potential of methanol extract of Basella alba leaves in male Wistar rats subjected to IIRI. Thirty male Wistar rats (200-250 g) were divided into five groups. Group A (sham operated) received normal saline (10 mg/kg) for two weeks. Group B was subjected to IIRI and also received normal saline. Groups C and D were pretreated with Basella alba extract at 100mg/kg and 200mg/kg, respectively, before IIRI. Group E received vitamin C (200mg/kg) prior to IIRI induction as a standard control. The study assessed cardiac oxidative stress parameters, inflammatory and cardiac injury markers, alongside histological evaluation. Results revealed that Basella alba-pretreated groups and the vitamin C group had increased levels of antioxidant enzymes-superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)-and reduced malondialdehyde (MDA), a lipid peroxidation marker. Inflammatory markers including myeloperoxidase (MPO), interleukin- 1β, interleukin6, and tumor necrosis factor- α were significantly reduced, while interleukin-4 levels were elevated. Cardiac injury markers such as troponin C and creatine kinase-MB were also significantly decreased. Histological assessment confirmed the biochemical findings, showing improved heart tissue architecture in treated groups. In conclusion, methanol extract of Basella alba demonstrated significant cardioprotective effects against IIRI, comparable to vitamin C at high dose. These findings support its traditional use and suggest its dietary inclusion could benefit individuals at risk of heart injury due to IIRI.

The rising concern about neglected tropical diseases imposes a global challenge, in this sense, this work brings 12 potential candidates based on chromone and phenol compounds to inhibit nsP2 and nsP3 of the Chikungunya virus (CHIKV), through molecular docking and ADMET evaluation. The molecular docking simulations for the nsP2 showed mild binding, in the nsP3 all the derivatives presented -6kcal/mol binding affinity and interacts with crucial residues in the replication cycle of CHIKV, the 5 best were chosen as the main derivatives for absorption, distribution, metabolism, excretion and toxicity (ADMET) evaluation). The ADMET results show high drug-likeness values, with good oral and intestinal absorption, excretion, distribution and toxicity, with moderate (Der9 to Der12) and poor (Der8) metabolism. Therefore, the 5 derivatives are potential candidates to treat chikungunya.

Circular RNAs (circRNAs), a distinct class of non-coding RNAs characterized by a covalently closed circular structure, have gained prominence as a promising research field due to their unique biological properties and functional roles relative to linear RNAs. This review summarizes recent progress in circRNA research, emphasizing fundamental mechanisms and translational potential. We first outline the discovery, biological features, synthesis, and purification of circRNAs. Next, their delivery systems, biological functions, and applications are reviewed. Finally, we discuss challenges and future prospects for clinical translation, with a focus on advancing precision medicine, gene therapy, and personalized vaccines. This review uniquely integrates recent advances in circRNA biology with their translational applications, offering a comprehensive perspective from molecular mechanisms to clinical potential.

Pain is a complex phenomenon involving the perception of physical discomfort caused by tissue damage in the body. Risperidone, a neuroleptic with dopamine (D2) and serotonin (5-HT2) receptor antagonistic potentials, also exhibits antinociceptive properties, however, its use in the treatment of peripheral nociception has received little attention. Hence, this study evaluated the antinociceptive effects of risperidone and its possible mechanism of action. Ninety Swiss mice (23-30 g) were divided into two phases: antinociceptive and mechanistic. Antinociceptive activity was assessed using acetic acid-induced writhing and formalin-induced paw-licking tests. In each model, mice were grouped (n=6) and treated with distilled water (control), risperidone (0.5,1.0, and 1.5 mg/kg), or indomethacin (10mg/kg). Mechanistic studies involved atropine, propranolol, or naloxone coadministered with risperidone (1.5mg/kg). The results of the studies showed that risperidone significantly decreased neurogenic and inflammatory pain in the paw licking test while risperidone 1.5mg/kg significantly decreased writhing in the acetic acid-induced writhing test. In the mechanistic studies, atropine co-administered with risperidone group showed significantly reversed anti-nociception when compared with risperidone 1.5mg/ kg alone in the paw-licking test model. Histological assessment of the mice paw tissues using Hematoxylin & Eosin, and Giemsa staining techniques revealed improved infiltration of inflammatory cells, which was significantly decreased in mice pre-treated with atropine, further supporting the analgesic potential of risperidone in the study. This study highlights risperidone's antinociceptive potential and suggests its mechanism is mediated via cholinergic pathways, offering insights into its therapeutic applications that can be implore in pain management.

Sepsis, a severe global health challenge characterized by life-threatening organ dysfunction stemming from a dysregulated immune response to drug-resistant pathogens, imposes a substantial disease burden. The intricate nature of sepsis necessitates meticulous drug administration and underscores the urgency for advanced drug delivery strategies. This paper presents a comprehensive overview of recent advancements in nanotechnologydriven therapeutic interventions for sepsis, emphasizing innovative approaches such as stimulus-responsive and nano-drug delivery systems that have been applied to tackle sepsis and its associated complications. Drawing from various theories and mechanistic insights into sepsis pathogenesis, we explore novel therapeutic avenues and their potential integration with nano-delivery systems, considering factors such as the microenvironment. We demonstrate how these nano-delivery systems can enhance treatment accuracy and diversity. Furthermore, the synergy between nanomedicine and emerging technologies like CRISPR, CAR-T therapy, AI, microfluidics, microbiome research, and immunotherapy holds the promise to revolutionize sepsis diagnosis, treatment, and management strategies. However, overcoming pathogen resistance, precisely modulating excessive immune response/immunosuppression, and achieving efficient targeted delivery of nanocarriers in complex pathological environments remain core challenges. Future research needs to focus on the development of smarter and more responsive nanoplatforms and deeply explore their deep integration with multiple cuttingedge technologies in order to advance the clinical translation of precision sepsis diagnosis and treatment.

Multidrug resistance (MDR) poses a critical barrier to chemotherapy efficacy. While the promising agents, aldose reductase inhibitors (ARIs), to overcome multidrug resistance (MDR) has been investigated over recent decades, their underlying mechanisms remain unclear and clinically viable candidates are still lacking. In our study, we identified a novel ARI, 5F-E, which exhibited a more potent sensitizing effect on doxorubicin (DOX) resistant HepG2 cells (HepG2/ADR) compared to epalrestat (EPA). Both 5F-E and EPA were observed to decrease intracellular GSH levels while elevating reactive oxygen species (ROS), Fe²⁺ and lipid peroxidation; these effects could be reversed by N-acetyl cysteine (NAC), suggesting that enhanced ferroptosis may be involved in restoring DOX sensitivity. Furthermore, inhibition of AKR1B1 by either compound led to marked reductions in p-STAT3 and SLC7A11 expression, an outcome that was recapitulated by AKR1B1 gene knockdown. The results demonstrate that ARIs exert antitumor effects on HepG2/ADR cells by triggering ferroptosis, a process dependent on AKR1B1/STAT3/SLC7A11 signaling. And, 5F-E, but not EPA, was found to increase intracellular DOX accumulation by inhibiting ABCB1. Our integrated experimental approach reveals that 5F-E exhibits strong chemosensitizing effects against multidrug-resistant liver cancer, highlighting its therapeutic promise.

RNA base editing, which enables RNA base modification through effector proteins guided by targeting systems, is a powerful technology to correct disease-associated point mutations. Although overshadowed by CRISPR-based genome editing, RNA editing has seen rapid development in recent years, with significant improvements in efficiency and precision. In this review, we summarize the core components of RNA base editing systems (RNAtargeting systems and effector proteins) and describe major RNA editing types, including A-to-I, C-to-U, A-tom⁶ A/m⁶ A-to-A, and U-to-$\mathrm{\Psi }$ base editors, along with their research progress. In addition, we systematically summarize the delivery methods of the developed RNA editors and their initial exploration in treating diseases caused by nonsense mutations. Finally, combining the current development status of the RNA editing related field, we reflect on the problems encountered in the current development of the RNA editing field and offer our own insights on the future development direction.

Single-cell multiomics (scMultiomics) technologies and methods encompassing transcriptomics, genomics, epigenomics, proteomics, and metabolomics, together with associated computational tools have profoundly revolutionized disease research, enabling unprecedented dissection of cellular heterogeneity and dynamic biological responses. The use of scMultiomics technologies to study drug drug screening, actions and responses has not only unlocked novel avenues in precision drug screening but also transformed our understanding of how small molecules target specific cell types in cancer treatment, as well as their connections to disease etiology and progression from a high-resolution view of their functional diversity. In this review, we systematically explore how scMultiomics technologies develop and drive advancements in drug screening. With a specific focus on the applications in target identification, drug response, and drug resistance, we highlight how scMultiomics can link cellular-level insights with individualized drug screening, which in turn promises actionable strategies to improve therapeutic precision in drug development.

Antibiotic resistance poses a serious global threat, contributing to severe clinical outcomes such as skin and soft tissue infections. Effective treatment of these infections requires both potent antimicrobial activity against resistant pathogens and wound dressings that can conform closely to the wound site. Degradable antimicrobial polymers offer a promising solution to this challenge. Unlike traditional antibiotic-loaded dressings, which often fail against multidrug-resistant (MDR) bacteria, antimicrobial polymers can effectively overcome resistance barriers. Moreover, these polymers can be easily incorporated into wound dressing materials-hydrogels being a particularly advantageous platform due to their biocompatibility and wound-conforming properties. In this study, we developed a modular strategy to integrate a biodegradable cationic antimicrobial oligomer, oligoamidine (OA1), into a thermo-responsive hydrogel. OA1 exerts a triple antibacterial mechanism involving membrane disruption, DNA binding, and ROS generation. The resulting hydrogel system can be conveniently formulated by simple mixing and undergoes a solution-gel transition at body temperature, enabling easy application to infected skin wounds. Importantly, the hydrogel matrix does not impair the bactericidal efficacy of OA1, preserving its full antimicrobial potential. This synergistic system offers an effective and user-friendly approach for treating wounds infected with MDR pathogens.

Malaria remains a major global health issue, particularly in endemic regions. Traditional medicine offers promising remedies, such as Melochia umbellata, a plant used in Cameroonian folk medicine for malaria treatment. While its in vitro antiplasmodial activity has been reported, the safety and curative efficacy of M. umbellata aqueous leaf extract (MULAE) in vivo required further investigation. This study evaluated the curative antimalarial and hepato-renal protective effects of MULAE in a Plasmodium berghei-infected rat model, alongside its phytochemical characterization. Qualitative and quantitative analyses confirmed the presence of pharmacologically active secondary metabolites, including alkaloids, phenols, flavonoids, and saponins. In acute toxicity tests (OECD guideline 423), female rats received single oral doses of MULAE (2000,5000mg/kg). No mortality or signs of toxicity were observed throughout the 14-day monitoring period, indicating an LD₅₀ greater than 5000mg/kg. For the curative assay, P. berghei-infected rats were treated for five days with MULAE (100, 200, 400mg/kg), chloroquine (10mg/kg), or distilled water. MULAE significantly suppressed parasitemia dosedependently; the 400mg/kg dose achieved 86.20% chemosuppression. The extract also improved hematological markers (restoring hemoglobin levels to 14.9 g/dL at 400mg/kg), mitigated infection-induced weight loss, and reduced organ damage. This organ protection was evidenced by improved blood serum markers (creatinine, ALAT, ASAT, bilirubin, total protein), restored oxidative status, and ameliorated histopathological changes in the liver, kidneys, and spleen. These findings validate the traditional use of M. umbellata and support its potential as a source for novel antimalarial and organ-protective agents.

The emergence of three-dimensional (3D) printing has represented a significant technological breakthrough, exerting a profound influence across various domains of society in recent times. There has been a noticeable shift in the healthcare industry's dominant paradigm of therapeutic interventions, particularly regarding the utilization of 3D printing technology to mend or replace damaged or missing biological components. Adopting cuttingedge technology can significantly enhance the range of applications within the field of oral healthcare. A significant amount of research is being conducted to leverage the substantial potential of 3D printing in oral applications, with a focus on developing customized treatment plans tailored to specific case scenarios. By building specialized implantology from different biological composite materials layer by layer, 3D printing technology precisely restores the anatomical structure of defects in the mouth and maxillofacial region. This review presents a comprehensive discussion on the history and classification of 3D printing technology, as well as the dynamics of biological materials, cells, and bioactive factors utilized in repairing oral and maxillofacial bone defects. Additionally, this review provides an update on the materials commonly used in typical oral healthcare applications and examines future trends and concerns related to material perspectives in oral healthcare management.

Viral drug resistance remains a critical challenge in antiviral therapy. This perspective highlights five studies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus type 1 (HIV-1), monkeypox virus (MPXV), influenza A virus (IAV), and Hepatitis B virus (HBV), revealing novel resistance mechanisms and innovative strategies. For SARS-CoV-2, GC376's flexible benzyl group overcomes nirmatrelvir resistance. HIV-1's non-nucleoside reverse transcriptase inhibitors (NNRTIs) 5i3 adapts to resistant mutants via a quinazoline scaffold, while MPXV's tecovirimat acts as a "molecular glue" stabilizing F13 dimers. Expanding these paradigms, we present groundbreaking insights: An indazole-based IAV inhibitor (compound 24) disrupts the conserved PA-PB1 heterodimer, showing sub-micromolar potency against resistant strains. For HBV, a hydrophobic tagging degrader (HyT-S7) induces HBc degradation, bypassing resistance mutations impairing traditional capsid modulators. Key strategies include dynamic flexibility, multivalent interactions, and oligomerization control, integrated with AI-driven design and real-time surveillance. This perspective bridges structural insights with translational applications, offering a roadmap for next-generation, mutation-resilient antivirals.

Suraxavir marboxil (GP681) is a promising novel prodrug influenza polymerase acidic (PA) inhibitor whose active metabolite, suraxavir (GP1707D07), is primarily metabolized by cytochrome P450 3A4 (CYP3A4), raising concerns about drug-drug interactions (DDI) with CYP3A4 inhibitors. Traditional DDI assessment methods are limited for evaluating all potential combinations. This study aimed to develop a physiologically based pharmacokinetic (PBPK) model to predict the DDI risk between GP681 and CYP3A4 inhibitors of varying potency. The model was developed based on physicochemical and in vitro parameters, as well as clinical data, including a phase I single ascending dose study of GP681 tablets and a single-center phase I study evaluating the DDI between GP681 and strong CYP3A4 inhibitor itraconazole. The model was successfully verified against clinical data, with predicted-to-observed ratios for GP1707D07 exposure under itraconazole co-administration of AUC and C_max  of 1.042 and 1.357, respectively. Simulations using the validated model predicted a substantial increase in GP1707D07 exposure when co-administered with moderate inhibitors fluconazole (AUC ratio 2.820 ; C_max  ratio 1.509) and verapamil (AUC ratio 2.347;C_max  ratio 1.645), comparable to the effect of itraconazole. Weak inhibitors showed negligible effects. Consequently, clinical monitoring and potential dose adjustment of GP681 are recommended when co-administered with strong inhibitors and the moderate inhibitors. The study demonstrates the utility of PBPK modeling for efficient and predictive DDI assessment of complex prodrug systems, guiding the safe clinical use of GP681.

Metal-organic frameworks (MOFs) have emerged as a highly versatile class of porous materials with significant potential to advance pharmaceutical research. This review provides a comprehensive overview of the current landscape of MOFs, encompassing their synthesis strategies, characterization methodologies, and diverse biomedical applications. We detail various synthesis approaches (e.g., hydrothermal, electrochemical, microwave) and essential characterization techniques (e.g., X-ray diffraction (XRD), scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) surface area analysis) that are critical for developing well-defined MOF structures. The review highlights the key advantages of MOFs in drug delivery, including their exceptional drug loading capacity, good biocompatibility, and capabilities for sustained, controlled, and targeted release. Their applications in improving drug solubility and stability, enabling pulmonary delivery, and functioning in biosensing, antimicrobial therapy, and nucleic acid delivery are also extensively discussed. Furthermore, we explore the utility of MOFs in drug structure analysis and the development of advanced functional systems, such as stimuli-responsive and self-propelled MOFs. Despite promising preclinical progress, challenges related to scalability, reproducibility, and long-term biosafety remain to be addressed for successful clinical translation. This work aims to bridge the gap between MOF materials science and pharmaceutical applications, offering valuable insights for the rational design of next-generation drug delivery systems and therapeutic platforms.

Cluster of differentiation-36 (CD36) is involved in cellular adhesion, lipid metabolism, immunity, and inflammation. Multiple studies have enlightened the regulatory roles of CD36 in metabolic reprogramming, metastasis, chemoresistance, stemness, immune modulation, senescence, inflammation, and angiogenesis. However, its role in tumorigenesis is still unclear and context-dependent. We performed a comprehensive pan-cancer analysis of CD36 by using data from TCGA, integrating transcriptomic, proteomic, methylation, mutational, immune infiltration, immunotherapy, and drug sensitivity datasets. Expression patterns, clinical associations, prognostic potential, immune interactions, and therapeutic implications were systematically evaluated. We also evaluated CD36-related molecular pathways and immune signatures in cancer by a comprehensive GSEA analysis. We found that CD36 expression pattern is dysregulated in multiple cancer types, whereas higher expression correlated with poor prognosis in LGG, BRCA, CESC, and LAML. CD36 mRNA showed inverse correlations with methylation levels. GSEA analysis revealed cancer-type-dependent association of CD36 with hallmark pathways, whereas multiple cancer types showed positive correlation with immune and inflammation-related pathways and negative correlation with cell cycle-related pathways. CD36 expression correlated with macrophage infiltration, immune regulators, and immunotherapy outcomes, including T-cell dysfunction and Immune checkpoint blockade (ICB) response. Moreover, drug sensitivity analyses revealed significant associations between CD36 and anticancer compound responses. This study provides a comprehensive and context-dependent landscape of CD36, establishing its oncogenic and immune-regulatory roles. Our findings highlight the potential of CD36 in prognosis, tumor microenvironment, and therapeutic sensitivity, while experimental validation is required to prove therapeutic relevance in cancer therapy and immunotherapy.

The research focuses on enhancing the delivery of curcumin's potent anti-inflammatory properties through a novel approach using a curcumin-loaded gelatine ethosomal gel. Curcumin, known for its therapeutic potential, faces challenges due to poor solubility and bioavailability. The method involved dissolving curcumin, phospholipids, and gelatin to form ethosomes within the gelatin matrix using sonication. Various parameters were evaluated including vesicle size, morphology, entrapment efficiency, drug permeation, stability, and antiinflammatory activity. The optimized curcumin gelatine ethosomes effectively encapsulated the drug, achieving an entrapment efficiency of 89.52%±0.1% and substantial drug loading capacity ranging from 75.75%±0.3% to 85.64%±0.1%. The formulation exhibited stability with a small vesicle size of 122.08 nm, a zeta potential of -36.2 mV indicating good stability, and spherical ethosome morphology. TEM images confirmed uniform drug distribution within the ethosome without precipitation or unwanted aggregates. The gel exhibited suitable characteristics for topical application such as clear texture, neutral odor, appropriate pH (5.1-5.6), and viscosity (26,000-58,000 Pa s). It also showed excellent spreadability, homogeneity, minimal irritancy, and pseudo plastic behaviour with sustained drug release (up to 94%) over 24 h. Stability testing and acute toxicity studies confirmed the safety and efficacy of the gel, while anti-inflammatory activity was demonstrated through carrageenan-induced rat paw edema model. The findings suggest that this curcuminloaded gelatine ethosomal gel holds promise in revolutionizing inflammation therapy by improving efficacy, patient compliance, stability, controlled release, and bioavailability, thereby paving the way for innovative approaches in inflammation management.

Chronic pain is a global health problem affecting approximately 30% of the adult population worldwide. Currently available painkillers often showed limited efficacy or serious adverse effects and require frequent administration to maintain therapeutic effects. To develop new long-acting analgesics with synergistic antinociceptive effects, a new co-drug INND-2201 of pregabalin and palmitoylethanolamide (PEA) was synthesized, characterized and prepared as a nanocrystal formulation. INND-2201 was slowly metabolized into pregabalin and PEA in microsomal stability test, and oral INND-2201 exhibited significant and synergistic antinociceptive effects for inflammatory and neuropathic pain with ED₅₀ values of 4.43 and 5.54mg/kg, respectively. Nanocrystals (NCs) of INND-2201 were then prepared by the ball milling method with the particle size of 107.1±2.7 nm. Intramuscular administration of INND-2201 NCs demonstrated prolonged pain relief lasting up to 5 days for chronic inflammatory pain in mice. Acute toxicity test, muscular irritation evaluation, rotarod test and open field test indicated that INND-2201 had a good safety profile. Taken together, INND-2201 NCs exerted long-acting analgesic effects and provided a promising strategy for the management of chronic pain.