Tissue Damage Research Articles

Epigenetic Regulation of Immune Cells in Health and Disease: A Comprehensive Review

Epigenetic regulation plays a crucial role in the development, differentiation, and function of immune cells. Mechanisms such as DNA methylation, histone modifications, chromatin remodeling, and non-coding RNA interactions dynamically shape gene expression, enabling immune cells to adapt to environmental stimuli and mediate appropriate immune responses. Aberrant epigenetic regulation is implicated in a range of diseases, including autoimmune disorders, cancer, and chronic inflammatory conditions. In autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis, altered DNA methylation and histone modifications contribute to immune dysregulation and tissue damage. In cancer, immune cells in the tumor microenvironment often exhibit epigenetic changes that facilitate immune evasion. Emerging therapeutic strategies targeting epigenetic pathways, including DNA methyltransferase inhibitors, histone deacetylase inhibitors, and CRISPR-based epigenome editing, offer promising approaches for treating immune-mediated diseases. This review provides a comprehensive overview of the epigenetic mechanisms governing immune cell behavior, their dysregulation in disease, and the potential of epigenetic therapies to restore immune homeostasis and improve patient outcomes. Keywords: Epigenetics, immune cells, DNA methylation, histone modifications, non-coding RNAs, autoimmune diseases, immunotherapy

Investigating Biomarkers and Molecular Mechanisms in COPD: Perspectives from In-vivo Models

Purpose: This review examines COPD pathogenesis, biomarkers, and treatment. COPD, a progressive respiratory illness that blocks airflow, causes high morbidity and death. The complicated pathophysiology of COPD involves genetic predisposition, environmental variables (particularly tobacco smoke), and inflammatory pathways. COPD diagnosis, prognosis, and monitoring depend on biomarkers in clinical and preclinical investigations. COPD care should include pharmaceutical and non-pharmacological therapies to improve symptoms, lung function, and outcomes. Materials and Method: This review examines COPD pathogenesis, cytokines, and risk factors. This review article discusses how immune system signalling molecules called cytokines contribute to COPD's persistent inflammation. Smoking and environmental contaminants are also examined as COPD risk factors. The analysis also covers biomarkers needed to diagnose and track the condition. Results: The review paper on COPD highlights the critical role of cytokines in the disease's pathophysiology, emphasizing their contribution to chronic inflammation. Various cytokines, particularly interleukins, are implicated in driving the inflammatory processes within the airways and lungs, resulting in tissue damage and airflow limitation, which are hallmark features of COPD. The paper also identifies smoking and exposure to environmental pollutants as major risk factors for the development of COPD. Conclusion: This review illuminates COPD's complex pathogenesis, highlighting cytokines' involvement in chronic inflammation. To create targeted therapeutics, cytokine-mediated pathways must be understood. The review emphasizes biomarkers' use in preclinical and clinical investigations to diagnose and monitor COPD and provide disease progression insights.

Exploring the potential of native sea urchins as ex situ coral propagation allies

Caribbean coral reefs face unprecedented decline due to anthropogenic and environmental stressors, necessitating active restoration efforts. Among the strategies to conserve and restore reef ecosystems, land‐based sexual propagation of corals is crucial for preserving genetic diversity and population resilience. This study explores the efficacy of utilizing native sea urchin herbivory to control benthic macroalgal proliferation and enhance coral growth in land‐based propagation systems. Three captive‐reared urchin species—Lytechinus variegatus, Tripneustes ventricosus, and Diadema antillarum—were evaluated for their influence on algal cover and growth of sexually propagated brain coral Pseudodiploria strigosa. Juveniles of each urchin species were co‐cultured with 6‐month‐old coral colonies over a 105‐day experiment. Results indicated that all urchin treatments effectively reduced algal cover compared to controls; however, only T. ventricosus significantly increased coral growth rate, while the other urchin species did not have a notable effect. Despite differences in growth, coral survival was consistently high across all treatments. Benthic community analysis revealed shifts in algal composition, with D. antillarum grazing associated with increased crustose coralline algae. However, overgrazing by D. antillarum may have resulted in mild peripheral tissue damage to some corals. Urchin survival remained high, suggesting potential for downstream utilization in restoration (e.g. urchin population enhancement). This study highlights the potential of native urchins as biocontrol agents in coral propagation, emphasizing the importance of species‐specific interactions in shaping benthic communities and promoting coral resilience.

Polystyrene microplastics cause reproductive toxicity in male mice

Microplastics are a common environmental pollutant that disrupts the reproductive system of living organisms. We investigated the reproductive toxicity of 2μm polystyrene microplastics (PS-MPs) in mice and treated them with PS-MPs for 6 weeks. We demonstrated that PS-MPs decreased the gonadosomatic index and the serum concentration of pituitary-testicular axis hormones (Follicle-stimulating hormone, Luteinizing hormone, and testosterone). The PS-MPs treatment also reduced viable epididymal sperm number and sperm motility. Our results also demonstrated a marked decrease in tubular differentiation index, spermatogenesis index, repopulation index, and steroidogenic foci. The PS-MPs treated mice demonstrated marketed tissue damage in the testis. We also found that reproductive abnormality in PS-MPs treated mice accompanied by reduced antioxidant capacity elevated oxidative stress, and, elevated apoptotic signaling. It was observed that Endoplasmic reticulum (ER) stress markers, including GRP78 and Chop, were upregulated. Based on these findings, oxidative stress and endoplasmic reticulum stress may contribute to the decline in the steroidogenic function of Leydig cells with PS-MPs treated.

Numerical modeling and analysis of neck injury induced by parachute opening shock.

Neck injuries from parachute opening shock (POS) are a concern in skydiving and military operations. This study employs finite element modeling to simulate POS scenarios and assess cervical spine injury risks. Validated against various conditions, including whiplash, the model replicates head/neck kinematics and soft tissue responses. POS simulations capture body/head motions during parachute deployment, indicating minimal risk of severe neck injuries (Abbreviated Injury Score/AIS ≥ 2) and low risk of soft tissue tears. Vertebral stress analysis during a rougher jump highlights high stress at C5/C6 lamina, indicating fracture risk. Comparative analysis with rear impact scenarios reveals distinct strain patterns, with rear impacts showing higher ligament strain, consistent with higher soft tissue damage risk. Though POS simulations exhibit lower strain values, they emphasize similar neck deformation patterns. The model's capability to accurately simulate head and neck movements during parachute openings provides critical validation for its use in assessing injury risks. The study's findings underline the importance of considering specific loading conditions in injury assessments and contribute to refining safety standards for skydiving and military operations. By highlighting the differences in injury mechanisms between POS and rear impacts, this research offers valuable insights into tailored injury mitigation strategies. The results not only enhance our understanding of neck injury mechanisms but also inform the development of protective gear and safety protocols, ultimately aiding in injury prevention for skydivers and military personnel.

Phytoremediation of microcystins using Myriophyllum aquaticum can prevent sublethal effects in a Neotropical freshwater catfish

Microcystins are cyanotoxins that can be produced by cyanobacteria species such as Microcystis aeruginosa. Due to the presence of microcystins in water bodies and aquatic organisms, it needs to be monitored. Furthermore, additional studies are required in the implementation of alternative and sustainable water treatment methods. The aim of this study was to investigate the potential of Myriophyllum aquaticum to prevent the harmful effects induced by M. aeruginosa aqueous extract in Rhamdia. quelen usingbiomarkers and to assess whether the plant can be suitable for phytoremediation in aquatic ecosystems. In the first experiment, R. quelen was exposed to 1 and 10 μg.L–1 of microcystins through an aqueous extract dissolved in the bioassay’s water. Second, tanks containing the same test concentrations of microcystins were treated by phytoremediation using M. aquaticum at 10 g.L–1, for 7 days. After that, treated water was used in a new bioassay with fish exposure. The results showed that phytoremediation decreased the microcystin concentration in water, and different biomarker analyses demonstrated that M. aquaticum treatment prevented DNA damage, hematological alterations, and tissue damage in R. quelen. The phytoremediation with M. aquaticum can be a sustainable and cost-effective alternative to water treatment, highlighting its role in enhancing water quality and supporting biodiversity conservation. These results support the importance of adopting more restrictive legal limits for cyanotoxins in water to protect native aquatic species and promote sustainable water resource management.

Acute kidney injury during transplantation and the role of inflammasomes: A brief review.

The increasing demand for an effective therapeutic modality in the form of organ transplantation leads to the need to improve the long-term outcomes of the process. Ischemia/reperfusion injuries (IRI) are an integral part of the kidney transplantation process, contributing to inflammation, oxidative stress and activation of the immune system. Inflammasomes, as a component of the immune response, in the form of inflammatory mediators during infection or tissue damage, initiate cell death called pyroptosis. In this context, we have defined the process of inflammasome activation in response to IRI, which is a potential cause of early kidney rejection due to increased susceptibility of the kidneys to ischemia. This review focuses on analyzing the modulation of inflammasome activity in kidney transplants and the activation of the NLRP3 inflammasome as a crucial element of kidney injury during the transplantation procedure, which could be a potential target for future preventive/therapeutic strategies.

The ameliorative potential of platelet-rich plasma and exosome on renal ischemia/reperfusion-induced uremic encephalopathy in rats.

Uremic Encephalopathy results from the elevation of toxins and blood-brain barrier (BBB) disruption. Renal Ischemia/Reperfusion (I/R) injury is the principal cause of acute kidney injury and brain tissue injury. The present study was crafted to estimate the restorative impact of platelet-rich plasma (PRP) and exosome injection before the reperfusion phase on the kidney following renal I/R injury and its influence on brain tissue by tracking the histopathological, biochemical, and Doppler ultrasonography alternations in both kidney and brain tissue. Forty mature male rats were divided into five groups as follows: control, I/R, PRP, exosome, and Exosome + PRP. Renal Doppler ultrasonography was traced for all rats. Serum kidney functions and acetylcholine esterase enzyme (AchE) were evaluated. Both Gamma-aminobutyric acid (GABA) and glutamate were assessed in brain tissues. The oxidative stress (malondialdehyde), anti-oxidative (glutathione and catalase), and pro-inflammatory (Tumor necrosis factor- α and interleukin-6) markers were estimated in renal tissues. Additionally, morphometric histological examination was performed in both renal and brain tissues. Both PRP and exosome-received rats exhibited a significant improvement in both serum kidney functions and AchE compared to I/R rats. There was a 3.39-fold increase in GABA and a 2.27-fold decrease in glutamate levels in the brain tissue of PRP rats compared to the I/R rats. A significant elevation (P ≤ 0.0001) of glutathione and catalase besides a significant reduction in the expression of TNF-α and IL-6 was observed in renal tissue compared to I/R rats. A significant severe reduction (P < 0.0001) in the number of Purkinje cells, pyramidal cells in the cerebellar cortex, and the CA1 region in the hippocampus was observed in I/R rats which was significantly alleviated by both PRP and exosome. Furthermore, there was a significant improvement in Doppler parameters. PRP exerted a significant superior impact on the restoration of kidney functions and repairing uremic-induced damage in brain tissue.

Metformin improves HPRT1-targeted purine metabolism and repairs NR4A1-mediated autophagic flux by modulating FoxO1 nucleocytoplasmic shuttling to treat postmenopausal osteoporosis.

Osteoporosis is a major degenerative metabolic bone disease that threatens the life and health of postmenopausal women. Owing to limitations in detection methods and prevention strategy awareness, the purpose of osteoporosis treatment is more to delay further deterioration rather than to fundamentally correct bone mass. We aimed to clarify the pathogenesis of postmenopausal osteoporosis and optimize treatment plans. Our experiments were based on previous findings that oxidative stress mediates bone metabolism imbalance after oestrogen deficiency. Through energy metabolism-targeted metabolomics, we revealed that purine metabolism disorder is the main mechanism involved in inducing oxidative damage in bone tissue, which was verified via the use of machine-learning data from human databases. Xanthine and xanthine oxidase were used to treat osteoblasts to construct a purine metabolism disorder model. The activity and differentiation ability of osteoblasts decreased after X/XO treatment. Transcriptomic sequencing indicated that autophagic flux damage was involved in purine metabolism-induced oxidative stress in osteoblasts. Additionally, we performed serum metabolomics combined with network pharmacology to determine the pharmacological mechanism of metformin in the treatment of postmenopausal osteoporosis. HPRT1 was the potential target filtered from the hub genes, and FoxO1 signalling was the key pathway mediating the effect of metformin in osteoblasts. We also revealed that SIRT3-mediated deacetylation promoted the nuclear localization of FoxO1 to increase the expression of HPRT1. HPRT1 upregulation promoted purine anabolism and prevented the accumulation of ROS caused by purine catabolism to reverse oxidative damage in osteoblasts. We propose that purine metabolism disorder-induced oxidative stress is important for the pathogenesis of postmenopausal osteoporosis. The therapeutic mechanism of metformin should be confirmed through subsequent drug optimization and development studies to improve bone health in postmenopausal women.

Commentary: the perspectives of harnessing the power of scattered tubular-like cells for renal repair.

The commentary discusses the regenerative capacity of the kidneys; recent studies reveal that renal cells can regenerate when exposed to certain conditions. A major focus is on scattered tubular-like cells (STCs), which can dedifferentiate and acquire progenitor-like properties in response to injury. These cells exhibit a glycolytic metabolism, making them resilient to hypoxic conditions and capable of repairing damaged renal tissues. Despite their potential, STCs are difficult to isolate and exist in small numbers. Here we highlight the need for more research into STC function, metabolic profiles, mechanisms limiting STC injury repair capacity, and methods of their pharmacological activation. Understanding these mechanisms could lead to novel therapies for kidney diseases.

Hypoxia adaptation mechanism in rats’ peripheral auditory system in high altitude migration: a time series transcriptome analysis

High altitude is characterized by low oxygen, low pressure, and high radiation. When migrates from low to high altitudes, the body’s tissues and organs experience hypoxic stress and will present acoustic adaptation as the protective response. However, the mechanisms of acoustic adaptation at high altitudes remain unclear. In this study, cochlear tissues from Wistar rats were collected at 15, 30, 60, 120, and 180 days after high-altitude migration. Transcriptome sequencing was conducted and DESeq algorithm revealed expression patterns of Differentially Expressed Genes(DEGs) after high altitude migration. Day 60 is a critical stage for cochlear tissue “damage” and “repair” in high-altitude conditions. Transmission Electron Microscopy (TEM) observations of structures also support the findings. A time-series gene co-expression network algorithm was used to investigate gene regulatory patterns and key genes after migration. Immunofluorescence, immunohistochemistry, and qPCR were per-formed for key gene validation and localization. At Day 60, the peak DEG count occurs in rats migrating to high altitude, aligning with the critical phase for cochlear tissue damage and repair at high altitudes. Repair hinges on synaptic plasticity and myelination-linked processes, influencing modules M4 to M6. Module M4’s activation gradually diminishes from its peak. However, the ‘damage’ effect is orchestrated by inflammation-related processes in modules M3 to M5, with module M3’s activation also waning. Key gene module M4, pivotal for repair during this pivotal phase, encompasses Sptbn5, Cldn1, Gfra2, and Lims2 as its core genes. Immunohistochemistry reveals Sptbn5’s presence in cochlear neurons, hair cells, Schwann cells and stria vascularis tissue. Cldn1 and Gfra2 predominantly localize within the cochlear neuron region. These results may suggest new directions for future research on acoustic acclimatization to high altitude.

The effect of melatonin and probiotics on radiation-induced enteritis in experimental rat models

Radiotherapy plays an important role in the treatment of tumors, and enteritis is a common side effect of this therapy. The aim of present study was to evaluate the protective effect of melatonin and probiotics on radiation-induced intestinal tissue damage in rats. Histopathological, biochemical and microbiological samples were examined. Thirty-two Wistar Albino rats were randomly distributed into four groups: the control group, only radiotherapy (RT) group, radiotherapy plus melatonin (RT + MEL) groups and radiotherapy plus probiotics (RT + PROB) groups. The abdominal-pelvic region of the experimental rat was irradiated with in a single dose of 16 Gy. The melatonin was administered at a single dose of 50 mg/kg through intraperitoneal injection, 15 min before radiation exposure. The probiotic was administered orally every day to the rats for 5 days starting before radiotherapy. There was a statistically significant changes in histopathological (villus atrophy, mitotic activity, apoptotic index, goblet cell swelling, degenerative changes, atypia) and biochemical (oxidant and antioxidant status, IL-1β, IL-6 and TNF- α levels) parameters in the small intestine in the radiotherapy group G2 compared to the G1 control group (p < 0.05). However, a significant decrease was observed with the administration of probiotics and melatonin (p < 0.05). In addition, although positive bacterial growth was detected in the mesenteric lymph node of all rats in the radiotherapy group, there was no statistically significant difference between all groups (p > 0.05). Melatonin and probiotics were found to have a potent radioprotective effect against radiotherapy-induced acute small intestinal tissue damage. However, their superiority over each other was not observed.

Glutamine modulates neutrophil recruitment and effector functions during sterile inflammation.

During sterile inflammation, tissue damage induces excessive activation and infiltration of neutrophils into tissues, where they critically contribute to organ dysfunction. Tight regulation of neutrophil migration and their effector functions is crucial to prevent overshooting immune responses. Neutrophils utilize more glutamine, the most abundant free α-amino acid in the human blood, than other leukocytes. However, under inflammatory conditions, the body's requirements exceed its ability to produce sufficient amounts of glutamine. This study investigates the impact of glutamine on neutrophil recruitment and their key effector functions. Glutamine treatment effectively reduced neutrophil activation by modulating β2-integrin activity and chemotaxis in vitro. In a murine in vivo model of sterile inflammation induced by renal ischemia-reperfusion injury, glutamine administration significantly attenuated neutrophil recruitment into injured kidneys. Transcriptomic analysis revealed, glutamine induces transcriptomic reprogramming in murine neutrophils, thus improving mitochondrial functionality and glutathione metabolism. Further, glutamine influenced key neutrophil effector functions, leading to decreased production of reactive oxygen species and formation of neutrophil extracellular traps. Mechanistically, we used a transglutaminase 2 inhibitor to identify transglutaminase 2 as a downstream mediator of glutamine effects on neutrophils. In conclusion, our findings suggest that glutamine diminishes activation and recruitment of neutrophils and thus identify glutamine as a potent means to curb overshooting neutrophil responses during sterile inflammation.

Challenges in tendon–bone healing: emphasizing inflammatory modulation mechanisms and treatment

Tendons are fibrous connective tissues that transmit force from muscles to bones. Despite their ability to withstand various loads, tendons are susceptible to significant damage. The healing process of tendons and ligaments connected to bone surfaces after injury presents a clinical challenge due to the intricate structure, composition, cellular populations, and mechanics of the interface. Inflammation plays a pivotal role in tendon healing, creating an inflammatory microenvironment through cytokines and immune cells that aid in debris clearance, tendon cell proliferation, and collagen fiber formation. However, uncontrolled inflammation can lead to tissue damage, and adhesions, and impede proper tendon healing, culminating in scar tissue formation. Therefore, precise regulation of inflammation is crucial. This review offers insights into the impact of inflammation on tendon–bone healing and its underlying mechanisms. Understanding the inflammatory microenvironment, cellular interactions, and extracellular matrix dynamics is essential for promoting optimal healing of tendon–bone injuries. The roles of fibroblasts, inflammatory cytokines, chemokines, and growth factors in promoting healing, inhibiting scar formation, and facilitating tissue regeneration are discussed, highlighting the necessity of balancing the suppression of detrimental inflammatory responses with the promotion of beneficial aspects to enhance tendon healing outcomes. Additionally, the review explores the significant implications and translational potential of targeted inflammatory modulation therapies in refining strategies for tendon–bone healing treatments.

Morphofunctional Features of Glomeruli and Nephrons After Exposure to Electrons at Different Doses: Oxidative Stress, Inflammation, Apoptosis

Kidney disease has emerged as a significant global health issue, projected to become the fifth-leading cause of years of life lost by 2040. The kidneys, being highly radiosensitive, are vulnerable to damage from various forms of radiation, including gamma (γ) and X-rays. However, the effects of electron radiation on renal tissues remain poorly understood. Given the localized energy deposition of electron beams, this study seeks to investigate the dose-dependent morphological and molecular changes in the kidneys following electron irradiation, aiming to address the gap in knowledge regarding its impact on renal structures. The primary aim of this study is to conduct a detailed morphological and molecular analysis of the kidneys following localized electron irradiation at different doses, to better understand the dose-dependent effects on renal tissue structure and function in an experimental model. Male Wistar rats (n = 75) were divided into five groups, including a control group and four experimental groups receiving 2, 4, 6, or 8 Gray (Gy) of localized electron irradiation to the kidneys. Biochemical markers of inflammation (interleukin-1 beta [IL-1β], interleukin-6 [IL-6], interleukin-10 [IL-10], tumor necrosis factor-alpha [TNF-α]) and oxidative stress (malondialdehyde [MDA], superoxide dismutase [SOD], glutathione [GSH]) were measured, and morphological changes were assessed using histological and immunohistochemical techniques (TUNEL assay, caspase-3). The study revealed a significant dose-dependent increase in oxidative stress, inflammation, and renal tissue damage. Higher doses of irradiation resulted in increased apoptosis, early stages of fibrosis (at high doses), and morphological changes in renal tissue. This study highlights the dose-dependent effects of electrons on renal structures, emphasizing the need for careful consideration of the dosage in clinical use to minimize adverse effects on renal function.

Muscle Tissue Response to Vipera berus berus and Vipera berus nikolskii Venoms: A Study on Matrix Metalloproteinases and Cytokine Modulation

Vipera berus, also known as the common adder, is a snake species widely distributed in Europe and parts of Asia. Its venom is a mix of enzymatic and non-enzymatic components causing both local and systemic effects including edema, hemorrhage, myonecrosis, gastrointestinal disorders, and rarely – rhabdomyolysis, coagulopathy and hypovolemic shock. Matrix metalloproteinases (MMPs) and cytokines, being inflammatory mediators, participate both in the development of these reactions and in tissue regeneration after acute damage. The current study was aimed at analyzing the concentrations of important mediators of tissue damage, inflammation and regeneration, namely, MMP-1, -2, -3, -8, -10, TIMP-1 (a tissue inhibitor of MMPs), and pro- and anti-inflammatory cytokines, in rat muscle after intraperitoneal injection of venoms from two subspecies of adders – V. berus berus and V. berus nikolskii — to clarify their role in the local response of skeletal muscle to the studied venoms. Changes in muscle tissue were revealed, namely, significant increase in almost all MMPs including MMP-2, as well as TIMP-1, IFN-γ and anti-inflammatory IL-4 and IL-10 content. Moreover, a tendency for some pro-inflammatory cytokines levels to decline 24 h after venom administration was observed, which may be a sign of inflammation suppression and the beginning of reparative processes associated with extracellular matrix remodeling and formation of an optimal environment for muscle regeneration. However, to establish the exact mechanisms of the changes we found, further studies are needed. The ability of V. berus nikolskii venom to induce more pronounced changes was also shown. Our results may be useful for the development of differentiated and more effective treatment strategies for the consequences of bites by these snakes, which include myonecrosis

Micro-CT study of human laryngeal structures using phosphotungstic agent staining.

Traditional dissection methods are primarily limited by challenges in identifying minute structures, which can lead to irreversible tissue damage. Anatomical observation of the larynx is particularly challenging in educational and clinical settings owing to its microscopic structures and complex three-dimensional (3D) nature, making it difficult to dissect. Therefore, this study aimed to demonstrate that micro-computed tomography (micro-CT) imaging of the larynx can serve as an effective alternative for educational and clinical purposes, overcoming these limitations. Three laryngeal specimens were obtained from cadavers, stained with a phosphotungstic acid-based contrast agent, and imaged using enhanced micro-CT. The resulting images were reconstructed in three dimensions, allowing for a detailed 3D observation of the specimens. Phosphotungstic contrast-enhanced micro-CT provided comprehensive anatomical information on laryngeal structures, including muscles, nerves, arteries, and vocal folds. This study demonstrates the high effectiveness of micro-CT in producing detailed structural images of the larynx, enabling 3D observation of even the smallest anatomical structures. These images can be applied in both educational and clinical settings to analyze the human larynx, effectively overcoming the limitations of traditional dissection methods. This approach facilitates the analysis of laryngeal structures that are otherwise difficult to observe with the naked eye.

Revolutionizing medicine: Recent developments and future prospects in stem-cell therapy.

Stem-cell therapy is a revolutionary frontier in modern medicine, offering enormous capacity to transform the treatment landscape of numerous debilitating illnesses and injuries. This review examines the revolutionary frontier of treatments utilizing stem cells, highlighting the distinctive abilities of stem cells to undergo regeneration and specialized cell differentiation into a wide variety of phenotypes. This paper aims to guide researchers, physicians, and stakeholders through the intricate terrain of stem-cell therapy, examining the processes, applications, and challenges inherent in utilizing stem cells across diverse medical disciplines. The historical journey from foundational contributions in the late 19th and early 20th centuries to recent breakthroughs, including ESC isolation and iPSC discovery, has set the stage for monumental leaps in medical science. Stem cells' regenerative potential spans embryonic, adult, induced pluripotent, and perinatal stages, offering unprecedented therapeutic opportunities in cancer, neurodegenerative disorders, cardiovascular ailments, spinal cord injuries, diabetes, and tissue damage. However, difficulties, such as immunological rejection, tumorigenesis, and precise manipulation of stem-cell behavior, necessitate comprehensive exploration and innovative solutions. This manuscript summarizes recent biotechnological advancements, critical trial evaluations, and emerging technologies, providing a nuanced understanding of the triumphs, difficulties, and future trajectories in stem cell-based regenerative medicine. Future directions, including precision medicine integration, immune modulation strategies, advancements in gene-editing technologies, and bioengineering synergy, offer a roadmap in stem cell treatment. The focus on stem-cell therapy's potential highlights its significant influence on contemporary medicine and points to a future in which individualized regenerative therapies will alleviate various medical disorders.

Clinical Effects of Thread-Dragging Therapy on Gangrene of Non-ischemic Diabetic Foot Ulcers.

To investigate the clinical effects of thread-dragging therapy on gangrene of non-ischemic diabetic foot ulcers (NIDFU). A total of 136 patients with NIDFU were recruited from the Department of Peripheral Vascular Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine between June 21, 2021 and February 1, 2023, and randomized into an intervention group and a control group, with 68 cases in each group. Both groups received basic treatment. The intervention group was treated with thread-dragging therapy, while the control group was treated with debridement combined with routine dressing changes after surgery. Both groups were treated continuously for 2 months. The amputation rates and changes in the ulcer area were compared between the groups. The inflammatory response index including peripheral white blood cells (WBCs), neutrophil percentage (NEUT%), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), and interleukin 6 (IL-6) were compared between the two groups. After treatment, the ulcer areas in the intervention group were significantly smaller than that of the control group (8.50±3.88 cm2 vs. 10.11±4.61 cm2, P<0.05). The amputation rates of the two groups were not statistically significant (4.4% vs. 5.9%, P>0.05). Differences of WBCs count, CRP, and ESR before and after therapy in the intervention group were better than the control group (P<0.05). However, there were no significant differences in changes of NEUT%, PCT, and IL-6 between the two groups (P>0.05). Thread-dragging therapy may be effective in the treatment of NIDFU, with the additional advantages of less tissue damage after healing. (Registration No. ChiCTR2100047496).

Expanding the Solvent/Protein Region Occupation of the Non-Nucleoside Reverse Transcriptase Inhibitor Binding Pocket for Improved Broad-Spectrum Anti-HIV-1 Efficacy: from Rigid Phenyl-Diarylpyrimidines to Flexible Hydrophilic Piperidine-Diarylpyrimidines.

Considering the nonideal antiresistance efficacy of our previously reported non-nucleoside reverse transcriptase inhibitor 7, a series of novel piperidine-diarylpyrimidine derivatives were designed through expanding solvent/protein region occupation. The representative compound 15f proved to be exceptionally potent against Y188L (EC50 = 23 nM), F227L + V106A (EC50 = 15 nM) and RES056 (EC50 = 45 nM), significantly better than 7. This analog exerted strong inhibition against wild-type HIV-1 (EC50 = 3 nM) and single mutant strains (L100I, K103N, Y181C, E138 K). Notably, its cytotoxicity and selectivity (CC50 = 18.23 μM, SI = 6537) were 4-fold better than etravirine and rilpivirine. Additionally, it exhibited minimal suppression of CYP isoenzymes and hERG, indicating low potential for drug-drug interactions and cardiotoxicity. No significant acute toxicity and tissue damage at a dose of 2 g/kg were revealed. These findings lay the groundwork for the advancement of 15f as a highly potent, safe, and broad-spectrum NNRTI for HIV therapy.