Search Results (353)

The tumor microenvironment (TME) in advanced solid tumors is determined by immune checkpoints (PD-1, CTLA-4, and CD95) and cytokine networks (IL-2, IL-10, and TNF-α) that drive CD8+ T cell exhaustion, metabolic reprogramming, and apoptosis resistance, enabling immune evasion. Some studies revealed PD-1/CD95 co-expression is a marker of T cell dysfunction, while CTLA-4 upregulation correlates with suppressed early T cell activation. IL-10 has emerged as a potential biomarker for chemoresistance and tumor aggressivity, consistent with its role in promoting anti-apoptotic signaling in cancer stem cells (CSCs). Engineered IL-2 variants and TNF-α modulation are highlighted as promising strategies to revitalize exhausted CD8+ T cells and disrupt CSC niches. This prospective single-center study investigated the dynamic TME alterations in 16 patients with immunotherapy-naïve stage IV non-small-cell lung cancer (NSCLC) and metastatic melanoma treated with anti-PD-1 nivolumab. The longitudinal immunophenotyping of peripheral blood lymphocytes (via flow cytometry) and serum cytokine analysis (via ELISA) were performed at the baseline, >3, and >6 months post-treatment to evaluate immune checkpoint co-expression (PD-1/CD95 and CTLA-4/CD8+) and the cytokine profiles (IL-2, IL-10, and TNF-α). Full article

The snakes from the genus Bothrops are responsible for most of the ophidic accidents in Brazil, and Bothrops atrox represents one of these species. Envenomation by these snakes results in systemic effects and is often associated with early mortality following snakebite incidents. The present study investigates the pharmacological properties of Bothrops atrox venom (VBA), focusing specifically on its impact on renal blood flow. Following the renal perfusion procedure, kidney tissues were processed for histopathological examination. Statistical analysis of all evaluated parameters was conducted using ANOVA and Student’s t-test, with significance set at p < 0.005. Administration of VBA resulted in a marked reduction in both perfusion pressure and renal vascular resistance. In contrast, there was a significant elevation in urinary output and glomerular filtration rate. Histological changes observed in the perfused kidneys were mild. The involvement of nitric oxide in the pressor effects of Bothrops atrox venom was not investigated in renal perfusion systems or in in vivo models. Treatment with VBA led to elevated nitrite levels in the bloodstream of the experimental animals. This effect was completely inhibited following pharmacological blockade with L-NAME. Based on these findings, we conclude that VBA alters renal function and promotes increased nitric oxide production. Full article

This study identifies the novel effects of soluble factors derived from murine erythroblasts on lymphoid cell phenotypes. These effects were observed following the treatment of splenic mononuclear cells with erythroblast-conditioned media received from both healthy mice and mice subjected to hematopoiesis-activating conditions (hypoxia, blood loss, and hemolytic anemia), suggesting a common mechanism of action. Using flow cytometry, we elucidated that erythroblast-derived soluble products modulate T cell differentiation by promoting Treg development and increasing PD-1 surface expression on B cells. The immunoregulatory potential of erythroblasts is subpopulation-dependent: CD45+ erythroblasts respond to hemolytic stress by upregulating the surface expression of immunosuppressive molecules PDL1 and Galectin-9, while CD45- erythroblasts primarily increase TGFb production. These findings highlight the regulatory role of erythroblasts in modulating immune responses. Full article

Atherosclerosis (AS), a progressive inflammatory disease of coronary arteries, the aorta, and the internal carotid artery, is considered one of the main contributors to cardiovascular disorders. Blood flow is restricted by accumulating lipid-rich macrophages (foam cells), calcium, fibrin, and cellular debris into plaques on the intima of arterial walls. Butyrate maintains gut barrier integrity and modulates immune responses. Butyrate regulates G-protein-coupled receptor (GPCR) signaling and activates nuclear factor kappa-B (NF-κB), activator protein-1 (AP-1), and interferon regulatory factors (IFRs) involved in the production of proinflammatory cytokines. Depending on the inflammatory stimuli, butyrate may also inactivate NF-κB, resulting in the suppression of proinflammatory cytokines and the stimulation of anti-inflammatory cytokines. Butyrate modulates mitogen-activated protein kinase (MAPK) to promote or suppress macrophage inflammation, muscle cell growth, apoptosis, and the uptake of oxidized low-density lipoprotein (ox-LDL) in macrophages. Activation of the peroxisome proliferator-activated receptor γ (PPARγ) pathway plays a role in lipid metabolism, inflammation, and cell differentiation. Butyrate inhibits interferon γ (IFN-γ) signaling and suppresses NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) involved in inflammation and scar tissue formation. The dual role of butyrate in AS is discussed by addressing the interactions between butyrate, intestinal epithelial cells (IECs), endothelial cells (ECs) of the main arteries, and immune cells. Signals generated from these interactions may be applied in the diagnosis and intervention of AS. Reporters to detect early AS is suggested. This narrative review covers the most recent findings published in PubMed and Crossref databases. Full article

Medicinal plants have been traditionally used for generations, often without scientific validation. Euphorbia tirucalli (E. tirucalli), a plant native to Africa, is commonly employed in folk medicine for treating various ailments, including cancer. However, most studies involving this species are limited to in vitro models, and its systemic effects remain poorly understood. This study aimed to evaluate the impact of E. tirucalli latex on renal function in healthy Wistar rats. Animals were divided into two groups: a control group receiving water and a treated group receiving E. tirucalli latex (13.47 mg/kg) by gavage for 15 days. Renal function was assessed by measuring glomerular filtration rate (GFR), renal plasma flow (RPF), renal blood flow (RBF), renal vascular resistance (RVR), and mean arterial pressure (MAP). Additionally, oxidative stress markers, reactive oxygen/nitrogen species, and inflammatory activity were analyzed in renal tissue. E. tirucalli significantly reduced GFR, RPF, and RBF, while increasing RVR and MAP. Renal tissue exhibited elevated levels of advanced oxidation protein products, myeloperoxidase, nitric oxide, and peroxynitrite/hydroxyl radicals. These findings indicate that E. tirucalli latex adversely affects renal hemodynamics and promotes oxidative and inflammatory damage, suggesting potential nephrotoxic effects, even in healthy subjects. Full article

Medical Infrared Thermography (MIT) is a safe, non-invasive technique for assessing temperature changes on the skin’s surface that may reflect pathological processes in the underlying tissues. In temporomandibular joint disorders (TMDs), which are often associated with reduced mobility and muscle overactivity, tissue metabolism and blood flow may be diminished, resulting in localized hypothermia. Aim: The purpose of this study was to evaluate muscle tone in the masseter, suprahyoid, and sternocleidomastoid muscles following the application of two types of occlusal splints, a Michigan splint and a double repositioning splint, based on temperature changes recorded using a Fluke Ti401 PRO thermal imaging camera. Materials and Methods: Sixty dental students diagnosed with TMDs were enrolled in this study. After applying the inclusion and exclusion criteria, participants were randomly assigned to one of two groups. Group M received a Michigan splint, while group D was treated with a double repositioning splint. Results: The type of occlusal splint influenced both temperature distribution and muscle tone. In the double repositioning splint group, temperature decreased by approximately 0.8 °C between T1 and T3, whereas in the Michigan splint group, temperature increased by approximately 0.7 °C over the same period. Conclusions: Occlusal splint design has a measurable impact on temperature distribution and muscle activity. The double repositioning splint appears to be more effective in promoting short-term muscle relaxation and may provide relief for patients experiencing muscular or myofascial TMD symptoms. Full article

Aging is associated with increased oxidative stress, which contributes to cellular dysfunction and age-related diseases. Pomegranate extract (PE), rich in antioxidant polyphenols, may help mitigate oxidative damage. This study evaluated whether PE supplementation modulates oxidative stress by reducing reactive oxygen species (ROS) levels in white blood cells of aging mice. Aged mice (18 months) were supplemented with PE for four months, and cytoplasmic and mitochondrial ROS levels were assessed in leukocytes under basal conditions and oxidative stress conditions induced by tert-butyl hydroperoxide (t-BHP) using flow cytometry. Our results indicate that aged mice exhibit increased basal ROS levels in both the mitochondrial and cytoplasmic compartments, which were mitigated by PE supplementation. Furthermore, PE reversed the increase in hydrogen peroxide levels induced by τ-BHP and protected neutrophils by reducing mitochondrial ROS levels. These findings suggest that PE supplementation modulates the oxidative stress response, potentially improving immune function in aging. Given the central role of oxidative stress in age-related decline, PE may represent a valuable nutritional strategy to promote healthy aging. Full article

Background: Exercise and nutritional interventions are often recommended to help manage risk related to metabolic syndrome (MetSyn). The co-ingestion of Phyllanthus emblica (PE) with trivalent chromium (Cr) has been purported to improve the bioavailability of chromium and enhance endothelial function, reduce platelet aggregation, and help manage blood glucose as well as lipid levels. Shilajit (SJ) has been reported to have anti-inflammatory, adaptogenic, immunomodulatory, and lipid-lowering properties. This study evaluated whether dietary supplementation with Cr, PE, and SJ, or PE alone, during an exercise and diet intervention may help individuals with risk factors to MetSyn experience greater benefits. Methods: In total, 166 sedentary men and women with at least two markers of metabolic syndrome participated in a randomized, placebo-controlled, parallel-arm, and repeated-measure intervention study, of which 109 completed the study (48.6 ± 10 yrs., 34.2 ± 6 kg/m², 41.3 ± 7% fat). All volunteers participated in a 12-week exercise program (supervised resistance and endurance exercise 3 days/week with walking 10,000 steps/day on non-training days) and were instructed to reduce energy intake by −5 kcals/kg/d. Participants were matched by age, sex, BMI, and body mass for the double-blind and randomized supplementation of a placebo (PLA), 500 mg of PE (PE-500), 1000 mg/d of PE (PE-1000), 400 µg of trivalent chromium (Cr) with 6 mg of PE and 6 mg of SJ (Cr-400), or 800 µg of trivalent chromium with 12 mg of PE and 12 mg of SJ (Cr-800) once a day for 12 weeks. Data were obtained at 0, 6, and 12 weeks of supplementation, and analyzed using general linear model multivariate and univariate analyses with repeated measures, pairwise comparisons, and mean changes from the baseline with 95% confidence intervals (CIs). Results: Compared to PLA responses, there was some evidence (p < 0.05 or approaching significance, p > 0.05 to p < 0.10) that PE and/or Cr with PE and SJ supplementation improved pulse wave velocity, flow-mediated dilation, platelet aggregation, insulin sensitivity, and blood lipid profiles while promoting more optimal changes in body composition, strength, and aerobic capacity. Differences among groups were more consistently seen at 6 weeks rather than 12 weeks. While some benefits were seen at both dosages, greater benefits were more consistently observed with PE-1000 and Cr-800 ingestion. Conclusions: The results suggest that PE and Cr with PE and SJ supplementation may enhance some exercise- and diet-induced changes in markers of health in overweight individuals with at least two risk factors to MetSyn. Registered clinical trial #NCT06641596. Full article

The abdominal drawing-in maneuver (ADIM) is one of the most valuable exercises for explicitly targeting and strengthening the transversus abdominis (TrA), a key muscle in the deep core. However, using the ADIM for the selective training of the transverse abdominis can be challenging for certain individuals. This study investigated the effects of combining ADIM with blood flow restriction (BFR) training on TrA strengthening in sedentary university students. Forty university students with sedentary lifestyles (mean age: 23.28 ± 2.468 years; range 20–25 years) were randomly assigned to an ADIM+BFR group and a control group (ADIM only). Both groups underwent 25 min ADIM training sessions twice weekly for four weeks. Ultrasound measurements assessed TrA thickness, contraction ratio, and preferential activation. Core stability, strength, and endurance were evaluated using the double leg lowering, abdominal strength, and abdominal static endurance tests. The ADIM+BFR group showed significant improvements in TrA thickness, contraction ratio, and preferential activation compared to the control group following the four-week training intervention (p < 0.05). The ADIM+BFR group demonstrated improved core stability and enhanced abdominal strength and endurance compared to the control group (p < 0.05). The results support the effectiveness of ADIM+BFR training in enhancing TrA contraction and activation in sedentary university students. This approach also improves core stability, strength, and endurance. BFR provides a novel and readily applicable method for promoting TrA activation during ADIM training. Full article

Transcranial pulse stimulation (TPS) is a non-invasive neuromodulation method that uses, high-intensity acoustic shockwaves to deliver focused mechanical stimulation to neural tissue with minimal thermal effects. The mechanism of action includes but is not limited to promotion of blood flow and angiogenesis through mechanotransduction. Clinical data to date are limited and preliminary. In Alzheimer’s disease (AD), TPS has demonstrated cognitive and mood improvements in pilot studies and secondary endpoint analysis in first randomized trials. The enhancement of gamma-band oscillations and network connectivity has been reported. Clinical observations in Parkinson’s disease (PD) suggest TPS as a hypothesis-generating approach to address non-motor symptoms—such as depression, cognitive decline, and the freezing of gait—through theoretical modulation of basal ganglia–cortical circuits. TPS is CE-marked in Europe for AD and shows a favorable safety profile; however, ethical considerations arise from the limited evidence base, potential impairment of patient autonomy and judgment in dementia, and the risk of withholding established treatments. TPS should only be offered under structured scientific protocols or within patient registries to ensure rigorous oversight. Ensuring that consent processes account for cognitive capacity, and that TPS is applied as adjunct rather than replacement therapy, is paramount. Future research must include large-scale randomized controlled trials (RCTs), standardize stimulation protocols, deepen mechanistic insight, and embed robust ethical frameworks. Full article

Objectives: This review explores the current evidence on how different massage modalities, either manual (MM) or using foam rolling (FR), with or without strength training, influence cardiovascular and autonomic function in healthy individuals. Methods: A search was performed in CINAHL, Cochrane Library, PubMed^®, and SciELO databases on 14 April 2025. Results: Among the 5125 studies retrieved in the database search, 7 were selected for the present review. The included studies pointed to an improvement in hemodynamic and autonomic responses, characterized by reduced arterial stiffness and blood pressure and an increase in nitric oxide concentration and blood flow. These findings suggest that physical exercise prescribers should consider the hemodynamic and autonomic effects promoted by massage (MM or FR). Conclusions: A change in arterial compliance, followed by a hypotensive effect on systolic blood pressure, reinforces the role of physical activity as a non-pharmacological agent and highlights the need for inclusion in the different groups that need adjuvant help for blood pressure control. Full article

Ischemic stroke (IS) is a disease characterized by disruption of blood flow to the brain, resulting in damage to brain tissue and neurological deficits. The high incidence of IS and the complexity of the underlying pathophysiology of IS have led to the need for further therapeutic development. It has been found that pericytes are indispensable multifunctional cells, which can coordinate multiple biological processes, and play a vital role in the development of IS. The purpose of this review is to provide a detailed overview of the role of pericytes in regulating vascular blood flow, maintaining BBB, regulating immune response, and promoting intracerebral fibrosis during the pathophysiological process after IS, which have dual effects on intracerebral recovery after IS. Finally, the article summarizes the current strategies targeting pericytes for the treatment of IS. Full article

Background: Chronic ischemic stroke presents a significant challenge in neurology, with limited therapeutic options available for long-term recovery. During cerebral infarction, anti-inflammatory phenotype microglia/macrophages produce anti-inflammatory cytokines and neurotrophic factors that facilitate the process of brain repair. However, obtaining sufficient anti-inflammatory microglia/macrophages from the human central nervous system is challenging. Bone marrow-derived inducible microglia-like cells (BM-iMGs) with an anti-inflammatory microglial phenotype were explored to induce neuroprotective properties. Here, we transplanted BM-iMGs into the brain of middle cerebral artery occlusion (MCAO) model male mice to explore their potential for treating chronic ischemic stroke. Methods: Bone marrow-derived mononuclear cells (BM-MNCs) were isolated from green fluorescent protein mice and incubated with granulocyte–macrophage colony-stimulating factor (GM-CSF) and IL-4 to induce BM-iMGs with an anti-inflammatory phenotype. BM-iMGs were transplanted into the brains of mice on day 14 after MCAO, and behavioral tests, histology, cerebral blood flow, and gene expression were evaluated. Results: An intracranial injection of BM-iMGs promoted neurobehavioral recovery, reduced neuronal cell loss, suppressed neuroinflammatory astrocytic and microglial responses in the brain, and increased cortical surface cerebral blood flow in MCAO mice. Furthermore, neuroprotective genes were upregulated, whereas proinflammatory genes were downregulated. Conclusions: The intracranial injection of BM-iMG cells shows significant potential as a novel therapy for chronic ischemic stroke. Full article

Peripheral artery disease (PAD) is a chronic progressive accumulation of atherosclerotic lesions with varying degrees of arterial obstruction determining ischemic symptoms of the involved extremities. PAD is associated with decreased bioavailable nitric oxide due to endothelial cell dysfunction and the development and progression of vascular arterial stiffening (VAS). Atherosclerosis also plays an essential role in the development and progression of vascular arterial stiffening (VAS), which is associated with endothelial cell activation and dysfunction that results in a proinflammatory endothelium with a decreased ability to produce bioavailable nitric oxide (NO). NO is one of three gasotransmitters, along with carbon monoxide and hydrogen sulfide, that promotes vasodilation. NO plays a crucial role in the regulation of PAD, and a deficiency in its bioavailability is strongly linked to the development of atherosclerosis, VAS, and PAD. A decreased arterial patency may also occur due to a reduction in the elasticity or diameter of the vessel wall due to the progressive nature of VAS and atherosclerosis in PAD. Progressive atherosclerosis and VAS promote narrowing over time, which leads to impairment of vasorelaxation and extremity blood flow. This narrative review examines how atherosclerosis, aging and hypertension, metabolic syndrome and type 2 diabetes, tobacco smoking, and endothelial cell activation and dysfunction with decreased NO and VAS with its increased damaging pulsatile pulse pressure result in microvessel remodeling. Further, the role of ischemia and ischemia–reperfusion injury is discussed and how it contributes to ischemic skeletal muscle remodeling, ischemic neuropathy, and pain perception in PAD. Full article

Background: Advancements in surgical wound management have led to improved healing and reduced complications. Incisional negative pressure wound therapy (iNPWT) is a technique that applies sub-atmospheric pressure to closed surgical wounds, enhancing blood flow, minimizing edema, and promoting tissue repair. Initially developed for chronic wounds, its use has expanded across multiple surgical specialties, including orthopaedic trauma surgery, to reduce complications such as dehiscence, infection, and prolonged healing. While traditional wound care relies on standard closure methods with simple dressings, iNPWT offers additional mechanical support and may lower the risk of deep surgical site infections (SSIs). This review examines the current evidence on iNPWT’s role in preventing SSIs following surgery for lower extremity fractures to guide clinical decision-making and improve patient outcomes. Methods: A systematic search through PubMed and MEDLINE utilizing our inclusion and exclusion criteria yielded seven randomized controlled trials and randomized prospective cohort studies that were subsequently analyzed to determine iNPWT effectiveness. Results: Of the seven studies, five showed a decreased SSI rate compared to standard wound dressing, with the other two exhibiting an increased infection rate. Conclusions: This review critically examines existing literature on iNPWT, analyzing level I and II studies on deep SSI rates in traumatic fractures. The evidence remains inconclusive on whether iNPWT offers a significant advantage over standard wound dressings, highlighting the need for further research to clarify its efficacy and clinical application. Full article