The demand for mass production of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) is escalating, driven by their potential to revolutionize cardiac regenerative therapies. The development of large-scale production protocols for iPSC-CMs is crucial to attain their therapeutic potential, enabling the treatment of millions of patients’ worldwide suffering from cardiovascular diseases. However, the scalable production of iPSC-CMs hinges on overcoming several critical challenges, including cellular differentiation and maturation. In pursue of tackling these challenges, researchers are investigating novel strategies such as prolonged culture periods, mechanical stimulation, and co-culture with supporting cell types. Overcoming these challenges is essential for unlocking the full potential of iPSC-CMs and paving the way for a new era in cardiac regenerative medicine. In this review, following topics are covered: (1) improvement of differentiation and maturation of iPSC-CMs and (2) scalable production of iPSC-CMs.

The intersection of phytonanotherapy, complementary and alternative medicine (CAM), and nanoparticles (NPs) promises an exciting new area in cancer and diabetes treatment. The CAM has attracted international recognition, emphasizing natural therapies and holistic health. Phytonanotherapy uses the promise of environmentally safe and sustainable green synthesis processes to develop NPs rich in bioactive chemicals originating from plants. These NPs provide a novel approach to targeted drug delivery, diagnostics, and therapy. Personalized medicine, tailoring therapies to individual genetic profiles and illness features, will most certainly be a cornerstone of these approaches in the future. The accuracy of NP-based drug delivery systems offers improved treatment outcomes while lowering systemic toxicity. Advanced diagnostics based on NPs and biosensors will enable early disease identification and real-time therapy response monitoring. Furthermore, combining CAM principles with NP-based therapies has great promise for holistic care. Combination therapies combining traditional medicine with cutting-edge nanomedicine have the potential to revolutionize cancer and diabetes care. These medicines will become more widely available provided an improvement in the regulatory approval process and accessibility. Individual preferences and well-being will be prioritized in patient-centered care, promoting a range of treatment options. Collaboration between practitioners of traditional medicine, researchers, artificial intelligence experts, and healthcare providers will improve complete and integrative health care. Green synthesis technologies will improve the efficiency and scalability of NP production. However, greater public and professional awareness is needed through educational initiatives to highlight the benefits and potential of CAM, phytonanotherapy, and NP-based treatments. To summarize, the future of CAM, phytonanotherapy, and NPs in cancer and diabetes treatment is bright since they provide patients with a variety of options while also contributing to more effective, sustainable, and patient-centered health care. To realize the full potential of these novel techniques, rigorous research, comprehensive clinical trials, and regulatory support will be required.

The subepithelial connective tissue graft (SCTG) has become the gold standard for treating gingival recession. In addition, SCTG is a reliable technique for augmenting the dimensions of attached gingiva and peri-implant mucosa, thereby supporting periodontal and peri-implant health and stability. Various autogenous soft-tissue harvesting techniques have been developed for use in periodontal plastic surgery, each with its own set of advantages and limitations. Over the past 5 years, updated reviews of human palatal anatomy have influenced clinical decision-making regarding SCTG harvesting, expanding the safety zone for palatal SCTG procedures. New histological and molecular findings have provided insights into the underlying mechanisms that may explain the observed differences in clinical outcomes based on the harvesting method and graft type. The purpose of this paper is to recommend a preferred SCTG harvesting technique applicable to most cases and to identify specific clinical scenarios where available evidence may support the use of alternative methods.

The incretin system is targeted in the treatment of type 2 diabetes mellitus (T2DM) and cardiovascular-kidney-metabolic (CKM) conditions. Increasingly, incretin hormones (i.e., gut peptides that enhance glucose-stimulated insulin secretion) reduce blood glucose levels, consequently alleviating CKM syndrome. Specifically, glucagon-like peptide 1 (GLP-1) demonstrated glucose-lowering effects, delayed gastric emptying, decreased glucagon secretion, and weight loss. An investigational medication, retatrutide, interacts as a tri-agonist with glucose-dependent insulinotropic polypeptide (GIP), GLP-1, and the glucagon receptor. Contemporary data indicate that early intervention, targeting not only the GLP-1 receptor but also the GIP and glucagon receptors, are forthcoming therapeutics affecting T2DM in earlier phases and CKM outcomes, demonstrating the advances in tri-agonists versus only GLP-1. Notably, endogenous levels of gut incretin hormones shift as pre-diabetes progresses to diabetes or regresses to normoglycemia. The present perspective provides a review of incretin therapy and its prospects in hindering the progression of T2DM and CKM syndrome.

This study focuses on radioactive contamination in the Urals, where the consequences were more severe in the long term than those after the Chernobyl accident. The difference is that the latter was a technogenic catastrophe, while the former was radioactive contamination tolerated for 70 years, with several accidents in between. In earlier publications by Russian researchers, no cancer frequency elevation was reported after exposures of <0.5 Sv or generally in the populations exposed to low doses. Later, the same scientists started to claim similar relative risks for cancer and other diseases among exposed people in the Urals and atomic bomb survivors in Japan. Apparently, there was an ideological shift in 2005 - 2007. Trimming of statistics was not unusual in the former Soviet Union. Potential motives included stirring antinuclear protests in other countries and the strangulation of nuclear energy aimed at boosting fossil fuel prices.

Tooth loss is a widespread condition that significantly impacts quality of life, and effective functional treatments remain limited. Research in regenerative technologies is advancing toward solutions that are functional, customizable, and biologically integrative. Tooth-germ organoids - three-dimensional constructs cultured in vitro - hold promise for developing functional dental tissues. Hydrogel microparticles, selected for their structural support, resemblance to the natural extracellular matrix, and moldability, serve as carriers and scaffolds for organoid culture. Methacrylate gelatin microspheres (GelMA MS) have previously been identified as suitable scaffolds for dental organoids, as they support the composition of multiple cell types necessary for forming functional dental tissue. However, producing GelMA MS at a scale sufficient for tooth-organoid research is time-consuming and suffers from limited reproducibility. This study aims to develop alternative gelatin-based carriers with simpler, more reproducible fabrication processes that provide equal or enhanced support for tooth-germ organoid formation. Two alternative carriers - gelatin microspheres (Gel MS) and micronized photo-crosslinked GelMA microparticles (GelMA MP) - were evaluated in comparison to GelMA MS and GelMA hydrogel. Both Gel MS and GelMA MP were found to be more cost-effective, easier to produce, and more reproducible than GelMA MS. To assess their effectiveness as cell carriers, the growth and osteogenic differentiation of human dental pulp stem cells (hDPSCs) were directly compared across all carriers. Results showed that hDPSCs demonstrated significant proliferation and formed organoid-like clusters on both Gel MS and GelMA MP, similar to GelMA MS. Cell viability was higher on GelMA MS, GelMA MP, and Gel MS than in GelMA hydrogel, a commonly used cell carrier. Among the four cell carriers, Gel MS provided the best support for the growth and osteogenic differentiation of hDPSCs. This study identifies viable alternatives to GelMA MS and highlights the superior performance of Gel MS as a cell carrier, advancing tooth-germ organoid research and developing potential therapeutic applications.

Much attention has been focused on studying the effects of obesity, particularly on the central nervous system (CNS). This study investigated the histoarchitecture of the prefrontal cortex (PFC) and hippocampus as well as the behavioral characteristics in male and female Wistar rats with diet-induced visceral obesity. The influence of a high-calorie diet on male and female rats reveals sex-specific changes in glial cells and the peculiarities of neurodegenerative processes in the PFC and hippocampal regions. In the context of visceral obesity, signs of depression were observed in male rats, whereas female rats showed no such signs. These results confirm the sex-specific effect of visceral obesity on the CNS.

The fruits of Schisandra chinensis (SCF) and Schisandra sphenanthera (SSF) are traditional Chinese herbal medicines classified as medicinal and food homologous materials, known for their significant neuroprotective efficacy. However, the differences in their therapeutic effects and active components for the treatment of vascular cognitive impairment (VCI) remain unclear. This study aimed to elucidate the neuroprotective activities of SCF and SSF on VCI and investigate the compositional disparities between the two. The lipopolysaccharide-induced and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced BV2 cell models were used to evaluate the protective effects of SCF and SSF against neuroinflammation and mitochondrial damage, respectively. The therapeutic effects were further validated using a bilateral common carotid artery stenosis mouse model. Compositional differences were analyzed using ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), and drug-like properties of their constituents were assessed. In vitro experiments showed that SCF and SSF at concentrations of 6.4, 16, and 40 μg/mL reduced nitric oxide, tumor necrosis factor-alpha, and interleukin-6 levels in a dose-dependent manner. Notably, at the same concentrations, SCF significantly mitigated OGD/R-induced mitochondrial damage, whereas SSF showed no significant effect. Compared with SSF, SCF exhibited stronger anti-neuroinflammatory and antioxidant properties. In vivo experiments further demonstrated that SCF, administered at 400 mg/kg, was more effective in improving learning ability, spatial learning and memory, cerebral blood flow, and nerve fiber repair than SSF. Moreover, 71 and 64 compounds were identified in SCF and SSF, respectively, using UPLC-Q-TOF/MS. Drug-like property analysis of these compounds revealed that the superior therapeutic effects of SCF may be attributed to differences in biphenylcyclooctene-type lignans. Our data support the conclusion that SCF possesses significantly superior neuroprotective activity compared to SSF, providing a theoretical basis for its clinical application in VCI.

Amyloidosis syndromes are characterized by the extracellular deposition of fibrillar proteins, with 22 systemic and 27 localized forms identified. Among these, amyloid A (AA) amyloidosis is a complication of chronic inflammatory diseases, particularly rheumatoid arthritis (RA), and can affect multiple organs, including the gastrointestinal (GI) tract. The study aimed to determine the prevalence and severity of systemic AA amyloidosis (sAAa) and GI AA amyloidosis (giAAa) in RA, evaluate their role in mortality, and clarify the diagnostic value of GI biopsy. A total of 161 randomly selected autopsy patients with RA were studied. In this study, the GI tract refers specifically to the stomach, small intestine, and large intestine. The presence and extent of sAAa and giAAa were assessed histologically; with AA deposition quantified using a semi-quantitative visual estimation scale ranging from 0 to 3. Demographic differences between patient cohorts were analyzed using the Student’s (Welch) t-test. sAAa was identified in 34 (23.13%) of the 161 patients. Among these cases, tissue blocks containing one or more sections of the GI tract were available in 31 patients. In 29 of these cases, AA deposits were detected in branches of blood vessels and various tissue structures of the GI tract, while giAAa was histologically excluded in two patients with sAAa. sAAa and giAAa may develop in both sexes and can occur at any stage in the course of RA. These conditions represent progressive and cumulative processes, initially affecting only a few structures within various organs and expanding in the later stages of the disease. Although giAAa does not appear to be a life-threatening complication of RA, it emerges as an early pathological feature of significant clinical and diagnostic importance, particularly as an optimal biopsy site.

Precise temperature regulation is essential for effective and safe magnetic resonance imaging-guided focused ultrasound (MRgFUS) treatments. Several variables influence the target temperature during sonication, with the energy delivered being a pivotal physical determinant. The skull density ratio (SDR) is utilized to evaluate the feasibility of treatment, with values below 0.3 - 0.4 generally considered contraindications for treatment. This study aimed to develop a robust predictive model for sonication parameters that can accurately achieve the desired temperature within the target tissue region. We obtained 152 treatment log data from the Insightec Exablate workstation. Variables, including power output, sonication duration, stop sonication button activation, SDR, age, sex, and initial sonication (ALIGN) parameters, were used as predictors (x), with the achieved temperature as the response (y), to construct the predictive models. RStudio was used to build linear models, and the TensorFlow library was employed for the neural network models. The linear and neural network models predicted tissue temperature with a mean absolute error of 2.78°C and 1.93°C, respectively, and a coefficient of determination of 0.71 and 0.76, respectively. The neural network model outperformed the linear model, demonstrating a smaller residual dispersion and a lower root-mean-square deviation. While the neural network model is more accurate and reliable for predicting MRgFUS temperatures, the linear model is easier to use. Key factors, such as sex, age, SDR, and the initial tissue response to the first sonication - the energy delivered during this initial treatment and the corresponding temperature - are crucial for optimizing subsequent sonication parameters such as power, energy, and duration.

This review highlights the importance of weight management in supporting metabolic health and healthy aging. By taking into account the genetic, environmental, and behavioral factors, effective weight management strategies can help reduce the risk of metabolic disorders and improve overall quality of life. The aging process is a multifaceted phenomenon influenced by a number of socioeconomic, biological, and psychological factors. In an aging society, the importance of healthy living and the significance of delaying aging process have increasingly gaining traction. The emergence of new medical and technological developments has led to the development of anti-aging methodologies designed to extend a healthy life span. Although aging is a natural process that can be accompanied by health problems, research shows that adopting a healthy lifestyle can help to delay and alleviate the negative effects of aging. Extensive clinical studies emphasize the importance of nutrition and regular physical activity in maintaining metabolic health in the healthy aging process. In summary, this review highlights genetic, environmental, and behavioral factors in weight management to support metabolic health and healthy aging, and evaluates the incorporation of personalized medicine in weight management as promising method of interventions to improve the healthy aging process.