Colorectal cancer (CRC) with liver metastases (LM) and peritoneal metastases (PM) presents a formidable challenge with poor prognosis despite advances in systemic chemotherapy and combined surgical approaches, including cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Median overall survival (OS) for such unresectable cases ranges from 12 to 24 months with modern regimens (e.g., 5-fluorouracil [5-FU], leucovorin, and oxaliplatin/5-FU, leucovorin, and irinotecan + targeted therapies). However, conversion to resectable diseases remains limited by disease extent and treatment toxicity. This paper proposes that medicinal mushroom extracts, particularly polysaccharides (e.g., polysaccharide krestin and polysaccharopeptide) from Trametes versicolor and bioactive compounds from species, such as Ganoderma lucidum, could enhance conversion therapy outcomes in CRC with LM and PM. Evidence from pre-clinical and clinical studies demonstrates that these extracts exert anticancer effects through multiple mechanisms, including suppression of multidrug resistance, blockade of immune checkpoints (e.g., programmed cell death protein 1/programmed death-ligand 1), regulation of oncogenic signaling pathways (e.g., phosphoinositide 3-kinase/protein kinase B, mitogen-activated protein kinase, and Nuclear factor kappa-light-chain-enhancer of activated B cells), and robust immunomodulation. Meta-analyses of over 8,000 patients reported improved survival and tolerability when combining the extracts with chemotherapy post-surgery. Similarly, meta-analysis in the present study, involving 2,397 patients, reveals a 10% relative increase in the probability of survival at 5 years, with a survival risk ratio of 1.10 (95% confidence interval: 1.04-1.15), based on post-operative data without direct pre-operative validation. Integrating these extracts into neoadjuvant regimens could enhance chemotherapy efficacy, increase surgical eligibility, and mitigate toxicity, potentially extending OS. While direct evidence in unresectable CRC with dual metastases is lacking, the biological plausibility and safety profile of mushroom extracts warrant prospective trials to validate their role in conversion therapy.

Phosphoinositide (PIP) lipids are master regulators of cellular signaling, membrane dynamics, and trafficking. Dysregulation of PIP signaling contributes critically to autoimmune disorders, where it disrupts immune tolerance and promotes inflammatory tissue damage. Similarly, viruses extensively exploit host PIP signaling pathways for entry, replication, and immune evasion. However, a comprehensive analysis linking PIP dysregulation across specific viral infections to autoimmune mechanisms is lacking. This review bridges this gap by decoding the intricate roles of PIP signaling in both viral pathogenesis and autoimmunity. We detail how eight distinct viral pathogens manipulate PIP networks and explore the resulting implications for autoimmune initiation or exacerbation. We synthesize findings on key PIP species, their effector proteins, and the modulated immune pathways central to both disease contexts. By elucidating these shared and unique mechanisms, this review identifies promising PIP-centric targets for therapeutic intervention in viral diseases and autoimmune disorders.

The advancement of combination antiretroviral therapy (cART) has dramatically transformed the management of human immunodeficiency virus (HIV), significantly reducing morbidity and mortality rates. However, the coexistence of sexually transmitted diseases (STDs) and antimicrobial resistance (AMR) presents interconnected challenges that compromise these advances in this era. This review explores the intricate associations between HIV, STDs, and AMR in the framework of extensive cART and antibiotic usage. Published literature on epidemiological data was analyzed to identify the patterns of co-infection and resistance trends, examining how the suppression of HIV influences the prevalence and treatment outcomes of concurrent STDs. Furthermore, the impacts of antibiotic overuse or misuse on the emergence of resistant strains of common bacterial STDs were investigated, particularly focusing on pathogens such as Neisseria gonorrhoeae and Mycoplasma genitalium among HIV-infected individuals. The findings highlight the critical need for integrated surveillance, antimicrobial stewardship, expanded vaccination, and culturally sensitive public health strategies. By enhancing our understanding of these interactions, this review intends to inform alterations in the existing public health policies and to upgrade previously optimized treatment protocols in the near future to improve patient outcomes in the era of cART and antibiotics.

Insights into the role of the gut microbiota are advancing our understanding of Alzheimer’s disease (AD), which is the most common cause of dementia and a condition characterized by progressive cognitive decline and pathological hallmarks such as amyloid beta (Aβ) plaques and neurofibrillary tangles. The gut microbiota, composed of diverse microorganisms, influences brain health through the microbiota-gut-brain axis. This review outlines how alterations in gut microbial composition and metabolites occur across different stages of cognitive decline. The microbiota-gut-brain axis mediates interactions between the gut and brain, influencing neuroinflammation, Aβ accumulation, tau pathology, and oxidative stress. Therapeutic strategies targeting gut microbiota, including diet modulation, probiotics, prebiotics, synbiotics, microbial metabolites, and fecal microbiota transplantation, have shown potential in improving cognitive function in clinical and animal studies. Despite these advances, challenges remain in addressing individual variability, standardization, and long-term safety. Personalized microbiota-based interventions may provide promising tools for the diagnosis, prevention, and treatment of AD.

The intricate relationship between the gut microbiota and the immune system has garnered significant attention in recent years, revealing a complex interplay essential for maintaining health and preventing disease. This perspective article delves into the dynamic interactions between the gut microbiota and the immune system, exploring how microbial communities influence immune development, function, and homeostasis. Emerging research highlights the impact of microbial metabolites, signaling pathways, and host genetics on immune responses. We also address the implications of microbiota-immune interactions in various diseases, including autoimmune disorders, infections, and cancer. Unraveling these complex interactions may provide a comprehensive understanding of the microbiota-immune system axis and its potential for guiding new therapeutic interventions. This article emphasizes the need for interdisciplinary approaches and advanced technologies to further elucidate the mechanisms underpinning this critical biological partnership.

Antimicrobial resistance is a silent pandemic threatening the lives of millions on the African continent. This exploratory study investigates microbial contamination of surfaces and medical devices, evaluates antibiotic resistance profiles, and identifies high-risk pathogens within a referral hospital in Yaoundé, Cameroon. A descriptive cross-sectional study was conducted from May to July 2024 in the obstetrics-gynecology department. Thirty samples were collected using sterile swabs from high-touch surfaces and from medical devices. Bacterial isolates were identified using standard culture and biochemical methods, and antibiotic susceptibility testing was performed through disk diffusion, with methicillin-resistant Staphylococcus aureus confirmed using cefoxitin discs. Data were analyzed using R Statistics version 4.4.2. The findings revealed that all samples were contaminated, yielding 55 bacterial isolates. Gram-positive bacteria were predominant (60%), primarily S. aureus (36%), and other Staphylococcus spp. (24%). Gram-negative pathogens included Proteus mirabilis (13%) and Klebsiella spp. (7%). Taps (14 isolates) and trolleys (100% contamination rate) were identified as the most contaminated sites. Antibiotic resistance was high: 70% of Staphylococcus species were methicillin-resistant, and 100% of Gram-negative isolates exhibited multidrug resistance (MDR), including resistance to penicillin (≥70%), cephalosporins (≥80%), and fosfomycin (≥75%). Carbapenems and quinolones remained effective against Gram-negative strains. These findings highlight widespread contamination of hospital environments with MDR pathogens, posing significant risks to maternal and neonatal health. The predominance of methicillin-resistant S. aureus and MDR Gram-negative bacteria underscores the urgent need to strengthen infection protocols, antimicrobial stewardship, and national antimicrobial resistance surveillance in Cameroon. Implementation of the World Health Organization infection prevention and control guidelines and targeted staff training is essential to reduce preventable healthcare-associated infections in resource-limited settings.

The emergence of multidrug-resistant (MDR) Gram-negative bacteria, including Escherichia coli and Pseudomonas aeruginosa, poses a critical global health challenge, necessitating innovative antimicrobial strategies. Leveraging Africa’s rich phytochemical diversity, this study integrates molecular docking and in silico pharmacokinetic profiling to identify natural compounds with dual-target potential. Ten bioactive phytochemicals from ethnomedicinal plants were screened against four validated bacterial targets: LasR (2UV0), AcrB efflux pump (5NC5), DNA gyrase B (6F86), and TEM-1 β-lactamase (1BTL) with AutoDock Vina implemented in PyRx, and the resulting protein-ligand interactions analyzed in Discovery Studio. Docking identified luteolin as exhibiting the highest binding affinity for LasR (−10.8 kcal/mol) and TEM-1, indicating dual inhibition of quorum sensing and β-lactamase activity. Rutin (−9.2 kcal/mol) exhibited high affinity for AcrB, indicating potential efflux pump inhibition, while ellagic acid (−8.3 kcal/mol) targeted DNA gyrase, potentially impairing bacterial replication. Absorption, distribution, metabolism, excretion, and toxicity analyses, along with ProTox-3 predictions, indicated that luteolin exhibited high gastrointestinal absorption and moderate systemic toxicity. Ellagic acid exhibited excellent biocompatibility, whereas rutin showed favorable drug-likeness but low permeability. Collectively, luteolin, rutin, and ellagic acid emerged as promising computational leads with complementary inhibitory mechanisms. This study highlights the translational potential of African phytochemical scaffolds in rational, computer-aided antimicrobial design and provides a foundation for subsequent in vitro and in vivo validation toward novel anti-MDR therapeutics.

Current guidelines recommend against administering the 9-valent human papillomavirus (HPV) vaccine during pregnancy due to limited safety data. We examined adverse events reported in patients receiving the 9-valent HPV vaccine during pregnancy. The Vaccine Adverse Events Reporting System (VAERS) database was queried for “exposure during pregnancy” to the 9-valent HPV vaccine. Cases were excluded if there was no information on pregnancy in the report or the patient was not pregnant at the time of vaccination. Individual reports were reviewed and data were extracted on gestational age and adverse pregnancy events. From the 285 reports identified, 273 were included. 40.3% (110/273) of the reports stated that there were no adverse events following vaccination. There were eight reports of mild maternal reactions (most commonly injection site pain) and one report of a serious reaction (angioedema). The majority of reports (257/273, 94.1%) did not include the pregnancy outcome. There was one case of vaginal bleeding, four miscarriages, one elective abortion, no stillbirths, and two congenital anomalies. There were seven reports of live births. 61.5% (168/273) of the reports included gestational age at the time of vaccination. Few cases of pregnancy-related adverse events were identified following 9-valent HPV vaccine administration. The VAERS database is an electively reported database; thus, the incidence of events could not be determined, and many reports were incomplete. Despite these limitations, the low numbers of adverse events are reassuring. Clinical trials are warranted to conclusively examine the safety and efficacy of HPV vaccination during pregnancy.

Real-time quantitative polymerase chain reaction remains the gold standard for COVID-19 diagnosis, but RNA extraction is time-consuming, expensive, and associated with increased biosafety requirements. This study evaluated an extraction-free dilution and heating (EFDH) method as a simplified alternative to conventional extraction-based (EB) real-time quantitative polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 detection. A total of 300 archived nasopharyngeal specimens, including 190 positives and 110 negatives, from the National Virology Reference Laboratory at the Ethiopian Public Health Institute, were analyzed. Samples were diluted 1:2 with RNase-free water, heated at 72°C for 15 min, and analyzed using an ABI 7500 Fast instrument. The EFDH method showed a sensitivity of 92%, a specificity of 100%, and an overall accuracy of 85.8%, producing 15 false-negative and 12 invalid results. Agreement with the EB method was high, with 95% concordance and a kappa coefficient of 0.89. Performance was strongest in samples with high viral loads (cycle threshold [Ct] < 20) and declined in those with low viral loads (Ct > 35). A significant correlation was observed between the two methods(R² = 0.99, p=0.001). These findings indicate that the EFDH approach reliably detects moderate-to-high viral loads and may serve as a practical testing option in resource-limited settings, especially during outbreaks when rapid and simplified workflows are needed.

Triple-negative breast cancer (TNBC) is an aggressive and metabolically distinct subtype of breast cancer characterized by immune evasion, a high reliance on glycolysis, and poor treatment outcomes. Given the limitations of conventional therapies, there is an urgent need for novel, targeted approaches that integrate immune stimulation with metabolic disruption. This review explores the potential of intratumoral Bacillus Calmette-Guérin (BCG) therapy as a dual-action strategy in TNBC, focusing on its ability to convert immunologically “cold” tumors into “hot” tumors when simultaneously targeting TNBC’s metabolic vulnerabilities. A comprehensive narrative review was conducted using PubMed, Scopus, and Web of Science, identifying 60 peer-reviewed studies published between 2000 and 2024. The selection criteria focused on BCG’s role in oncology, its immunological and metabolic effects, and its application in solid tumors. Studies were assessed for methodological rigor using the Scale for the Assessment of Narrative Review Articles checklist. BCG enhances antitumor immunity by engaging Toll-like receptors, triggering proinflammatory cytokine release (e.g., tumor necrosis factor alpha, interferon gamma, and interleukin-12), and promoting the infiltration of tumor-infiltrating lymphocytes, including cytotoxic T-cells and natural killer cells. This immune activation reprograms the tumor microenvironment, increasing susceptibility to immunotherapy. Simultaneously, BCG disrupts TNBC’s glycolytic dependence by downregulating hexokinase 2 and pyruvate kinase M2, forcing a metabolic shift toward oxidative phosphorylation. This metabolic stress induces mitochondrial dysfunction, reactive oxygen species accumulation, and tumor cell apoptosis. In addition, BCG-induced “trained immunity” epigenetically reprograms innate immune cells, enhancing long-term tumor surveillance and reducing recurrence risk. Intratumoral BCG presents a promising immunometabolic intervention for TNBC by simultaneously enhancing immune activation and disrupting tumor metabolism. Future studies should focus on optimizing its clinical application, developing sustained-release formulations, and exploring synergistic combinations with immune checkpoint inhibitors and metabolic inhibitors. By addressing TNBC’s dual vulnerabilities, this strategy may redefine treatment paradigms and improve patient outcomes.

Acute disseminated encephalomyelitis (ADEM) is a demyelinating, immune-mediated inflammatory condition of the central nervous system (CNS). It can affect individuals of all ages. The case definition for monophasic ADEM includes polyfocal clinical CNS events of inflammatory origin, with magnetic resonance imaging showing large (>1 cm) diffuse white matter lesions, absence of relapse for 3 months, and exclusion of other acute demyelinating disorders. ADEM can also be associated with various infections and vaccinations. Our case study suggests that ADEM occurs following intralesional measles, mumps, and rubella (MMR) vaccination to treat cutaneous warts. This case highlights the importance of making a well-informed decision regarding the risk of demyelinating disease in patients receiving vaccines. In addition, it emphasizes the need to obtain a detailed vaccination history when assessing patients with suspected ADEM. This is the first documented case of ADEM following intralesional MMR vaccination.

The chemokine receptors possess seven transmembrane helices connected by an extracellular N‐terminal region, three extracellular loops (ECL1-3), three intracellular loops, and an intracellular C‐terminal region. Specific monoclonal antibodies (mAbs) against chemokine receptors for flow cytometry have been developed using Cell-Based Immunization and Screening, and the N-terminal peptide immunization methods. However, there are few reports on the establishment of anti-chemokine receptor mAbs through immunization with ECL peptides. Here, an anti-mouse C-C chemokine receptor type 7 (mCCR7) mAb, C₇Mab-2 (rat immunoglobulin G_2b, kappa), was established through immunization with the ECL3 peptide. C₇Mab-2 demonstrated reactivity to mCCR7-overexpressed Chinese hamster ovary-K1 (CHO/mCCR7) cells in flow cytometry, which was inhibited by the ECL3 peptide. C₇Mab-2 did not show cross-reactivity with other mouse CC, CXC, CX3C, and XC chemokine receptors. The dissociation constant value of C₇Mab-2 was determined to be 2.8 × 10⁻⁹ M for CHO/mCCR7 cells. Furthermore, C₇Mab-2 detected mCCR7 in immunohistochemistry. This strategy could accelerate the development of novel chemokine receptor mAbs with high affinity and specificity.