This study aimed to characterize biochemical and microenvironmental changes within the Disc Vertebra Complex (DVC) in non-specific low back pain (NSLBP) patients using non-fat-saturation Multi-slices CEST MRI. By performing intra-group comparisons, we assessed associations between disc degeneration and vertebral biochemical variations. Ninety-nine NSLBP patients (62 males, 37 females; median age 45) underwent lumbar spine MRI. Non-fat-saturation Multi-slices CEST imaging was used to assess fat fraction (FF), fat /water content and magnetization transfer contrast in vertebrates, and water content, glycosaminoglycan (GAG), amide proton transfer (APT), nuclear overhauser enhancement (NOE) and magnetization transfer contrast in discs. Metabolic and microenvironmental changes across vertebrae (L2-S1) and intervertebral discs (L2/3-L5/S1) were analyzed. Statistical comparisons were conducted across disc grades, weight categories, and disc abnormalities. Significant biochemical variations were observed across vertebral levels, with decreasing water content and increasing FF from L2 to S1. The pH-sensitive markers (APT) showed caudal trends, indicating relative changes in proton environment. Protruding discs and discs with high-intensity zones (HIZ) showed reduced pH and hydration, alongside altered macromolecular structures. Adjacent vertebrae of protruding discs exhibited decreased water content, indicative of early bone marrow edema. Non-fat-saturation Multi-slices CEST MRI enables holistic profiling of the disc-vertebra complex (DVC) and detects localized, grade-dependent biochemical heterogeneity. Notably, differences emerged between vertebrae and discs with and without protrusion / HIZ, alongside grade-dependent variations.
Monocrotaline (MCT), a plant-derived pyrrolizidine alkaloid, is well known for its hepatotoxic effects. However, full elucidation of the mechanisms underlying MCT-induced hepatotoxicity, as well as the development of reliable biomarkers for early detection and monitoring, requires an integrated evaluation of biochemical, molecular, and histopathological data. This study aims to evaluate the hepatotoxic effects of MCT using biochemical, molecular, and histopathological data. Thirty male BALB/c mice were randomly assigned to three groups: control, acute toxicity, and subacute toxicity. The control group received saline, the acute group received a single dose of 120 mg/kg MCT, and the subacute group received the same dose administered three times at 5-day intervals. Blood and liver tissues were collected for biochemical and oxidative stress analysis. Apoptotic markers were evaluated at the protein and gene expression levels using ELISA, qPCR, and PCR array. Histopathological examination was performed to assess structural liver alterations. MCT significantly increased hepatic enzyme levels including ALT, GGT, and TBIL, while AST levels showed a nonsignificant numerical increase and were associated with disrupted lipid and protein metabolism, evidenced by increased TCHO and decreased TP. Oxidative stress markers (TOS, OSI) increased in the acute group with reduced TAS, whereas TAS increased in the subacute group, indicating temporal modulation of antioxidant defenses. Bax and caspase-3 were upregulated, and Bcl-2 was downregulated at the protein level. qPCR corroborated these findings at the transcriptional level, although without statistical significance. Histopathological analysis revealed extensive hepatic injury, particularly in the acute toxicity group. The findings indicate that MCT induces liver injury via enzymatic dysregulation, oxidative stress, and apoptosis and highlight the need for further research to identify reliable biomarkers for the early detection and monitoring of MCT-induced hepatotoxicity.
Aging is associated with progressive cognitive decline and reduced neurobiological resilience that increase vulnerability to anxiety-related dysfunction. Although aerobic exercise is known to support brain health, whether different exercise modalities exert distinct behavioral and neurobiological effects remains unclear. This study aimed to investigate the effects of moderate continuous and extensive interval aerobic exercise on behavioral outcomes and underlying neurobiological mechanisms in aged male rats. Thirty-two male Sprague Dawley rats (24 aged, 8 young adults) were randomly assigned to four groups (n = 8 per group): moderate continuous exercise (MCE; 0.5 km/h, 0° incline, 30 min), extensive interval exercise (EIE; alternating 5 min at 0.5 km/h and 1 min at 1.0 km/h, 30 min total, 0° incline), aged control, or young control. Following treadmill acclimatization, exercise was performed three days per week for six weeks. Anxiety-like behavior was assessed using the open field and elevated plus maze tests, and spatial learning and memory were evaluated with the Morris water maze. Serum, hippocampal, and gastrocnemius muscle samples were analyzed for brain-derived neurotrophic factor (BDNF), superoxide dismutase (SOD), glutathione peroxidase (GPx), and interleukin-10 (IL-10). Statistical analyses were conducted using one-way and repeated-measures ANOVA with Bonferroni post-hoc tests. Compared with aged controls, EIE reduced thigmotaxis in the open field test p = 0.035, d = 1.20), while no differences were observed in the elevated plus maze. Both exercise groups accelerated spatial learning across Morris water maze training days (p < 0.001). EIE was associated with improved memory retention, reflected by increased target quadrant time during the probe trial (p = 0.013, d = 1.35). Biochemically, EIE increased BDNF, IL-10, and SOD levels in serum and hippocampus (p < 0.05), whereas MCE selectively enhanced hippocampal GPx activity. Both exercise modalities elevated GPx levels in muscle and serum compared with aged controls (p < 0.05-0.001). Aerobic exercise was associated with changes in behavioral performance and neurobiological markers in aging rats. Interval-based training was associated with more pronounced changes in certain cognitive and biochemical parameters compared to moderate continuous exercise. These findings suggest that different exercise modalities may differentially influence selected cognitive and redox-related outcomes during aging.
Metanephrine-secreting adrenocortical carcinoma has been rarely described in humans and, to our knowledge, has not been previously confirmed in dogs. A 12-year-old castrated male Maltese was referred for an incidentally detected left adrenal mass. The dog had persistent systemic hypertension (160-210 mmHg) and urinary normetanephrine and metanephrine-to-creatinine ratios above the reference range, findings suggestive of pheochromocytoma. Computed tomography revealed a homogeneously enhancing adrenal mass without overt vascular invasion. After preoperative phenoxybenzamine therapy, laparoscopic adrenalectomy was performed. Histopathology demonstrated adrenocortical carcinoma with vascular tumor emboli. Immunohistochemistry demonstrated diffuse Melan-A positivity and chromogranin A negativity, with synaptophysin immunoreactivity in corresponding tumor regions on serial sections, supporting adrenocortical origin with partial neuroendocrine differentiation. Postoperatively, urinary catecholamine metabolite concentrations normalized, and serial blood pressure monitoring at approximately monthly re-evaluations documented no recurrence of systemic hypertension without antihypertensive therapy over an 11-month postoperative follow-up period, supporting the adrenal cortical tumor as the source of the preoperative biochemical and hemodynamic abnormalities.
Parkinson's disease (PD) is a chronic neurodegenerative disorder that leads to motor and non-motor challenges, significantly impacting the quality of life. Research highlights body's antioxidant systems role in mitigating PD. This study investigated neuroprotective capabilities of Tinospora sinensis stem extract (TSSE) in a rat model of PD induced by rotenone. PD was induced in rats by subcutaneous rotenone injections (2 mg/kg/day) for 35 days. TSSE was administered orally at 100, 200, and 400 mg/kg doses, with levodopa-carbidopa as the standard reference. Motor impairments were assessed through catalepsy, locomotor activity, and rotarod tests. Biochemical evaluations included oxidative stress markers, antioxidant enzymes (glutathione, superoxide dismutase, and catalase), and dopamine levels, and monoamino oxidase-B (MAO-B). Histopathological examination of brain assessed neuronal integrity. Rotenone administration led to significant motor impairments, increased oxidative stress, reduced dopamine levels, and neuronal damage. Treatment with TSSE resulted in notable, dose-dependent enhancements in motor abilities and restored antioxidant enzyme activities, while also reducing lipid peroxidation, as indicated by decreased malondialdehyde levels. Additionally, TSSE decreased MAO-B level and increased brain dopamine level and maintained neuronal structure. The TSSE 400 mg/kg exhibited neuroprotective effects comparable to those of standard. TSSE shows significant neuroprotective effects, likely by enhancing endogenous antioxidant defenses and restoring dopaminergic neurotransmission. These findings suggest, TSSE could serve as a complementary therapeutic approach that targets oxidative and neurodegenerative mechanisms in PD.
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Sensorineural hearing loss is a major public health concern, yet its treatment remains limited by the anatomical complexity and biological barriers protecting the cochlea. Among these, the round window membrane (RWM) constitutes a key interface for local drug delivery to the inner ear. However, passive diffusion via intratympanic injection is often insufficient, particularly for hydrophilic, large, or negatively charged molecules such as gene therapy vectors. This systematic review aimed to evaluate biomechanical and biochemical strategies to enhance RWM permeability for more efficient and targeted drug delivery to the inner ear, including direct permeability modulation of the RWM properties or indirect enhancement mechanisms increasing drug delivery without altering intrinsic membrane permeability. Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a comprehensive literature search was conducted using the Scopus, MEDLINE/PubMed, Cochrane, and CINAHL electronic databases. In vivo studies and clinical trials involving biochemical or biomechanical strategies to enhance RWM permeability were included. Risk of bias was assessed using the SYRCLE (Systematic Review Center for Laboratory Animal Experimentation) tool. Out of 1776 screened articles, 89 met the inclusion criteria. Four biochemical approaches and three biomechanical strategies were identified, respectively: (1) hydrogels, thermogels, and emulsions, (2) nanosystems, (3) microsystems, and (4) permeabilizers, and (1') sonoporation, (2') acoustic stimulation, and (3') magnetic systems. Most studies reported improved drug delivery to the inner ear or therapeutic efficacy. While earlier research focused on hydrogels, thermogels, emulsions, permeabilizers, and acoustic stimulation for small molecules such as corticoids and antioxidants, recent studies increasingly explore nanosystems, microsystems, sonoporation, and magnetic methods to facilitate the delivery of larger agents, including gene therapy. This review also highlights that while many strategies are already available and effective in animal models, further research is essential to facilitate the clinical translation of both existing and emerging delivery methods.
The association of prostate-specific antigen (PSA) persistence after radical prostatectomy (RP) with inferior prognosis was demonstrated in a systematic review. However, all patients in the included studies lacked a prostate-specific membrane antigen Positron-Emissions-Tomography (PSMA-PET) before salvage radiotherapy (SRT). Since PSMA-PET has markedly improved sensitivity in detecting lymph node and distant metastases, it is unclear whether PSA persistence can be further considered a risk factor in patients or reflects an advanced tumor stage. We used a retrospective database including 1222 PSMA-PET-staged prostate cancer patients treated with SRT for biochemical recurrence (BR) at 11 centers in five countries. After patients without information on PSA persistence were excluded, 1188 patients remained. The effects of PSA persistence and recurrence on overall survival (OS), metastasis-free survival (MFS), and biochemical progression-free survival (BPFS) were evaluated. The median follow-up time was 31.0 months (IQR range: 20.04-43.6 months). PSMA-PET revealed a higher incidence of local recurrence (43.5% vs. 30.0%, p = 0.01), and lower incidence of nodal failure in patients with PSA recurrence (40.6% vs. 30.5%, p < 0.001). In univariate analysis, patients with PSA recurrence had significantly superior 3-year biochemical progression-free survival (BPFS) (71.5% vs. 63.0%, p = 0.033) and MFS (83.0% vs. 78.0%, p = 0.049) compared with patients with PSA persistence. In the multivariate analysis, no significant differences were observed concerning BPFS (p = 0.738), MFS, (p = 0.826), or OS (p = 0.730). PSA persistence, traditionally considered a hallmark of a worse prognosis, may require reevaluation considering advances in imaging sensitivity. While our analysis does not definitively determine whether PSA persistence is no longer prognostic, it remains possible that its historically poorer prognosis and early focal detection via PSMA PET/CT have been therapeutically mitigated. As PSMA-PET becomes more widely available, its ability to detect hidden disease may help guide individualized treatment decisions.
To investigate integrated biochemical and glycomic signatures in humans related to coordinated metabolic and endocrine adaptations during prolonged fasting, which are essential for maintaining systemic homeostasis. This single-arm longitudinal interventional study enrolled five healthy adults who underwent a 72-hour water-only fast. Blood samples were collected at baseline (T0), immediately after fasting (T1), and after 11 days of refeeding (T2). A broad panel of biochemical, hormonal, inflammatory, and glycomic parameters was determined. Time-dependent differences were evaluated using the Friedman test. Fasting induced a distinct biphasic response across multiple circulating markers, with significant alterations in total cholesterol, C-reactive protein, thyroid-stimulating hormone, and free triiodothyronine at T1 followed by recovery toward baseline at T2. Insulin and glucose concentrations declined during fasting and increased after refeeding, although these changes did not reach statistical significance. Plasma, immunoglobulin G (IgG), and IgA N-glycosylation profiles were extensively remodeled, which indicated dynamic metabolic and immune system adaptation. Liver enzymes, electrolytes, and most lipid fractions exhibited only minor and reversible fluctuations. A 72-hour fast was associated with metabolic and hormonal changes consistent with an environment conducive to autophagy, although autophagy was not measured directly. The protocol appeared feasible and well tolerated in a small cohort of healthy adults. Given the limited sample size, these findings should be considered preliminary and require confirmation in larger studies incorporating direct autophagy markers and additional time points.
Type 2 diabetes (T2D) accounts for over 90% of all diabetes cases and results from the interaction of genetic and environmental factors. However, the association between apolipoprotein E (APOE) gene polymorphisms and T2D risk shows considerable variation across different populations. This meta-analysis aims to clarify the association between APOE genotypes and alleles (E2E2, E2E3, E2E4, E3E4, E4E4) and the risk of T2D. Additionally, it examines the association of demographic, clinical, and biochemical parameters with T2D risk in cases and controls. Relevant articles providing genotypic and allelic frequencies of APOE polymorphisms were sourced from Google Scholar, Web of Science, Science Direct, and PubMed databases. These articles focus on peer-reviewed human case-control studies published in English until February 27, 2024. Data on APOE polymorphisms, biochemical, and clinical parameters were extracted. Statistical tests were performed using Review Manager 4.3.1 with results expressed using ORs and 95% CIs. Publication bias and heterogeneity were assessed using the Q test and Egger regression analysis. Thirty-two studies involving 19644 participants. The statistical analysis showed that BMI, SBP, DBP, TC, and LDL-C could potentially indicate a higher risk of T2D in cases compared to controls. Significant associations with T2D were found for the APOE E4E4 genotype (OR =1.94, 95% CI= [1.16, 3.23], P = 0.01, I2=75%), and the E4 allele (OR=1.26, 95% CI= [1.11, 1.43], P = 0.0005, I2=55%). No significant associations were observed for the E2E2, E2E3, E2E4, and E3E4 genotypes, or the E2 allele (P > 0.05 for all). A significant association between APOE genotype E4E4 and allele E4 with T2D was confirmed in this meta-analysis.
Plants have evolved multilayered mechanisms against microbial pathogens. We highlight work from Wang and colleagues, demonstrating the biochemical and genetic basis of plant chemical defenses against cross-kingdom viral, bacterial, and fungal pathogens, while conceptualizing a new classification system for these multifaceted resistances based on core genetic defenses.
To investigate the effect of β-Sitosterol on interleukin (IL)-1β-induced chondrocyte injury and the related mechanism. An osteoarthritis model was constructed by treating immortalized human cartilage cells with IL-1β. The identity and purity of β-Sitosterol were confirmed by FTIR, 1H NMR, 13C NMR, RP-HPLC-ELSD, and UPLC-MS before cell experiments. The optimal concentrations of IL-1β and β-Sitosterol for treating cells were determined by qPCR and CCK8 assay. The cells were divided into three groups: Control group, Model group, and Model+β-Sitosterol group. Cell viability was detected by CCK8 assay. The mRNA expression of IL-18, IL-1β and tumor necrosis factor-α (TNF-α) was detected by qPCR. Collagen type II alpha 1 chain (COL2A1) and matrix metalloproteinase 13 (MMP13) expression was detected by immunofluorescence. Reactive oxygen species (ROS) and mitochondrial membrane potential were detected by flow cytometry. Malondialdehyde (MDA), Glutathione (GSH) and Fe2+ were detected by ELISA and biochemical test. Mitochondrial structure was observed by transmission electron microscopy, and the protein expression of ferroptosis related factors was detected by Western blot. After induction of chondrocytes with IL-1β, the cell viability was decreased, the gene expression of inflammatory cytokines was increased, the proportion of cells with reduced ROS content and mitochondrial membrane potential were increased, MDA and Fe2+ content were increased, and GSH content was decreased. Mitochondrial structure showed ferroptosis-like changes. The expression of COL2A1, glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), total nuclear factor erythroid 2-related factor 2 (NRF2), and nuclear NRF2 was decreased. MMP13, ANO6, and p-p38/p38 levels were increased. Treatment of chondrocytes with β-Sitosterol could reverse these changes induced by IL-1β. Spectrally confirmed, high-purity β-Sitosterol alleviated IL-1β-induced chondrocyte injury by suppressing inflammatory activation, extracellular matrix degradation, mitochondrial dysfunction, and ferroptosis-related oxidative damage, suggesting its potential as a candidate compound for osteoarthritis intervention.
Chronic kidney disease (CKD) is a global health burden with high prevalence and poor prognosis. Although oxidative stress and mitochondrial dysfunction have been implicated in its pathogenesis, in vivo causal evidence remains limited. Thioredoxin (Trx), encoded by Txn1, is a redox-active protein that plays a central role in controlling oxidative stress and maintaining intracellular redox homeostasis. To address this gap, we investigated the lifelong phenotypes of Txn1-F54L mutant rats harboring approximately one-third of the normal Trx activity. These rats were generated via N-ethyl-N-nitrosourea mutagenesis and validated by clustered regularly interspaced palindromic repeat (CRISPR)/CRISPR-associated protein 9 genome editing. Comprehensive analyses included biochemical testing, histopathology, immunohistochemistry, transmission electron microscopy, RNA-sequencing, western blotting, and cytokine profiling. Txn1-F54L mutant rats spontaneously developed progressive CKD, with median survival times of 110-119 days for homozygotes and 303-346 days for heterozygotes. Their clinical features-elevated blood urea nitrogen, hypoalbuminemia, hypercholesterolemia, hypertension, and arterial medial sclerosis-closely resembled those of human CKD. Histopathological evaluation revealed extensive tubular injury, interstitial fibrosis, and glomerulosclerosis. Transcriptomic profiling identified 3,418 differentially expressed genes significantly enriched in immune activation and fibrosis pathways. Mitochondrial dysfunction was prominent in proximal tubules, accompanied by oxidative stress accumulation and concurrent activation of regulated cell death pathways (apoptosis, necroptosis, and pyroptosis). Elevated serum levels of interleukin-1β, interleukin-6, and interferon-γ indicated systemic inflammation. Our findings demonstrate that lifelong Trx deficiency induces oxidative stress-mediated mitochondrial dysfunction and regulated cell death, leading to inflammation and progressive CKD. This study establishes the Txn1 mutant rat as a valuable spontaneous CKD model, providing translational insights and a platform for developing therapeutic strategies targeting oxidative stress-induced pathways.
Micro(nano)plastics (MNPs) often coexist with antibiotics in soil ecosystems via organic fertilizer applications. They can be taken up and accumulated by plants, especially food crops, thereby threatening food safety. Despite increasing global concern, the distinct phytotoxic mechanisms of MNPs and their interactive dynamics with antibiotics remain dispersed. First, the uptake, translocation, and distribution of MNPs in plants are systematically synthesized. Based on the clarification of plant phenotypic and physiological responses to MNP stress, the review assesses their biochemical and molecular mechanisms, ranging from oxidative stress and antioxidant defense to signal transduction and transcriptional regulation to metabolic trade-offs. After clarifying the physicochemical interactions and cotransport mechanisms between MNPs and antibiotics, the review elucidates their combined phytotoxicity and their crucial role in antibiotic resistance gene (ARG) transmission in soil-plant systems. Finally, we identify research gaps and propose future research directions, which will facilitate the evaluation of ecological risks and the formulation of environmental regulations for copollutants.
The present study investigated the individual and combined effects of lactic acid and rosemary meal on growth performance, biochemical parameters, immune responses, the expression of growth and antioxidant-related genes, intestinal morphology, and oxidative status in Nile tilapia (Oreochromis niloticus). A total of 120 apparently healthy fish, with an average weight of 3.03 ± 0.02 g, were randomly assigned to four equal groups, each consisting of three replicates. Four experimental diets were formulated: a basal control diet (CON), a basal diet supplemented with 1 g of lactic acid per kg of diet (LA), a basal diet containing 10 g of rosemary per kilogram of diet (RM), and a basal diet that included both supplements (LA + RM). Fish were fed these diets for a duration of 60 days. The results indicated that either lactic acid or rosemary alone or in combination had a greater growth-stimulating impact than the CON group (P ≤ 0.05) with superiority to the combination group (LA + RM group). Activities of aspartate aminotransferase and alanine aminotransferase, along with creatinine and urea levels, were significantly reduced (P ≤ 0.05) in the groups of lactic acid and rosemary alone or in combination relative to the CON group. Total protein and albumin concentrations were elevated in the LA + RM group (P ≤ 0.05). Intestinal histology revealed normal morphology across groups, with increased villus height, intestinal villi spacing, and goblet cell density in LA + RM (P ≤ 0.05) without pathological lesions in the liver and spleen. Antioxidant, immune, and growth-related gene expressions were upregulated in RM and LA + RM groups. In conclusion, rosemary supplementation, alone or combined with lactic acid, enhanced fish health status and upregulated target genes without pathological lesions with superiority to the combination treatment.
L-proline, an amino acid with antioxidant properties, has demonstrated significant potential in counteracting oxidative stress and preserving sperm quality. This study evaluated the protective effects of L-proline against heat stress-induced damage during sperm preparation incubation, a critical step in assisted reproductive technologies (ART). Semen samples from 30 normozoospermic men were divided into two groups: a control group and a treatment group supplemented with 2 mmol/L L-proline. Following initial incubation at 37 °C for 30 min, samples were further subdivided and subjected to controlled thermal exposures at 25 °C, 37 °C, and 42 °C for both short-term (3 h) and long-term (24 h) incubation periods, simulating physiological and heat-stress conditions. Sperm parameters, including motility, viability, morphology, and biochemical markers of oxidative stress, including catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (TAC), malondialdehyde (MDA), and nitric oxide (NO), were comprehensively assessed. Results indicated that heat stress exposure significantly impaired sperm function and disrupted redox homeostasis. Supplementation with 2 mmol/L L-proline significantly preserved sperm motility and viability during heat stress conditions compared to the control group (p < 0.05). However, no significant protective effect on sperm morphology was observed. Additionally, L-proline enhanced antioxidant defenses by improving CAT, SOD, and TAC levels while concurrently modulating MDA and NO levels under heat stress conditions (p < 0.05). In conclusion, these findings highlight the potential of L-proline as a protective supplement to ameliorate the detrimental effects of heat stress on human sperm quality and oxidative status, suggesting that incorporating L-proline into sperm preparation protocols may offer a promising strategy to enhance clinical outcomes.
This study investigates the therapeutic efficacy and safety of Onco-VV-TT, a genetically engineered oncolytic vaccinia virus, in the treatment of glioblastoma (GBM), with and without the combination of natural killer (NK) cell immunotherapy. A comprehensive set of in vitro and in vivo experiments was conducted to assess viral cytotoxicity, replication, tumor penetration, and immunomodulatory effects. Onco-VV-TT selectively reduced the viability of GBM cell lines (U251, U87, and C6) in a time- and dose-dependent manner while sparing normal fibroblasts. The virus significantly impaired clonogenicity, migration, and stemness-related gene expression in U251 cells. Confocal imaging confirmed viral replication and deep penetration into 3D spheroids. NK cells demonstrated strong cytotoxicity against U251 cells in both 2D and 3D models. In a xenograft mouse model, intratumoral administration of Onco-VV-TT suppressed tumor growth and significantly prolonged survival; NK cell monotherapy showed limited efficacy, while the addition of NK cells further enhanced therapeutic outcomes. Immunological analyses revealed that combination therapy elevated pro-inflammatory cytokines (TNF-α, IFN-γ, and IL-6) and increased WBC count, reflecting an expected transient systemic inflammatory response to vaccinia virus exposure rather than a direct enhancement of antitumor immunity. Histopathological and immunohistochemical analysis showed reduced mitosis, increased apoptosis, decreased cancer stem cell marker CD133, and lower VEGF expression in tumors treated with Onco-VV-TT and NK cells. Safety evaluations in immunocompetent mice demonstrated no significant systemic toxicity or organ damage following intravenous injection of Onco-VV-TT. Transient inflammatory marker elevation resolved by day 21, and all hematological and biochemical parameters remained within normal range. These findings suggest that Onco-VV-TT, particularly in combination with NK cell therapy, is a promising and well-tolerated approach for GBM treatment, meriting further preclinical and clinical development.
Percussive therapy (PT) is increasingly used for post-exercise recovery, but its effects and dose-related responses after exercise-induced muscle damage remain uncertain. This review evaluated the effects of PT on neuromuscular performance, muscle soreness, and biochemical markers after acute exercise. The study adhered to PRISMA guidelines. A comprehensive search was conducted across PubMed, Embase, Web of Science, the Cochrane Library, and CNKI for Randomized Controlled Trials (RCTs) published through November 26, 2025. Risk of bias, methodological quality, and certainty of evidence were assessed using RoB 2, PEDro, and GRADE. Data analysis was performed using Stata-MP 18.0 software. Twelve RCTs were included. PT improved countermovement jump recovery compared with control (k = 13, g = 0.78, 95% CI 0.26 to 1.29, p < 0.01; low certainty) and reduced creatine kinase levels (k = 7, g = - 0.87, 95% CI - 1.57 to - 0.17, p = 0.02; very low certainty). PT did not clearly improve maximum voluntary contraction recovery (k = 8, g = 0.12, 95% CI - 0.10 to 0.34, p = 0.28; moderate certainty) or delayed onset muscle soreness (k = 17, g = 0.14, 95% CI - 0.19 to 0.48, p = 0.40; very low certainty). Exploratory analyses suggested that longer treatment (> 5 min per muscle group) was associated with larger countermovement jump effects, whereas 2.5-5 min protocols at higher frequency (≥ 50 Hz) were associated with creatine kinase reduction. Longer treatment was also associated with higher delayed onset muscle soreness scores. PT may improve explosive performance recovery and reduce early creatine kinase levels, but current evidence does not support clear benefits for maximum strength recovery or soreness relief. Dose-related findings are preliminary and should not be interpreted as prescriptive thresholds.
Polystyrene nanoplastics (PS-NPs) are an emerging class of environmental contaminants with increasing concern regarding their potential effects on reproductive development. This study examined whether maternal lactational exposure to PS-NPs is associated with alterations in ovarian growth, structure, and function in female rat offspring. The dams were administered PS-NPs at doses of 0, 0.1, 1, or 10 mg/kg/day exclusively during the 21-day lactation period. Female offspring were evaluated on postnatal days 30 (PD30) and 60 (PD60). Macroscopic assessments indicated dose-related reductions in body weight, ovarian weight, and ovarian length at both postnatal stages in females. Qualitative fluorescence microscopy using rhodamine-labeled PS-NPs revealed dose-related fluorescent signals within the follicular and stromal compartments of the ovary at PD30 and PD60, supporting particle localization in ovarian tissue. Histological and morphometric analyses revealed a reduction in pre-antral follicle numbers at PD30, progressive thinning of the granulosa layer, and a decreased parenchyma-to-stroma ratio, particularly in high-dose offspring. Biochemical analyses indicated oxidative imbalance, characterized by an elevated total oxidant status (TOS) and oxidative stress index (OSI) at PD30, along with a reduced total antioxidant capacity (TAC) and higher oxidative indices at PD60. Endocrine evaluation at PD60 showed dose-related decreases in circulating estradiol and progesterone levels. Immunohistochemical analysis demonstrated increased P53 immunoreactivity and reduced BCL-2 expression, consistent with apoptosis-related signaling in ovarian tissue. Collectively, these findings suggest that lactational exposure to PS-NPs is associated with dose-related ovarian alterations accompanied by oxidative imbalance, endocrine disruption, particle localization, and apoptosis-associated responses, highlighting lactation as a potentially sensitive postnatal exposure window.
Decidualization of endometrial stromal cells is a critical process for establishing uterine receptivity and successful embryo implantation, involving coordinated biochemical, cellular, and biomechanical remodeling. Emerging evidence indicates that this process is associated with activation of endoplasmic reticulum stress (ERS) and the development of distinct stromal subpopulations, including mature and senescent decidual cells. However, how these pathways integrate to regulate the mechanical properties of the endometrium remains unclear. Here, we investigated the impact of decidualization dysregulation on stromal cell nanomechanics and its contribution to implantation failure. Our first approach used an in vitro decidualization model of human endometrial stromal cells (cell line HESC), in which an excessive ERS was induced by thapsigargine. Then, decidualization, senescence and UPR were evaluated by molecular analyses, cellular nanomechanical properties by atomic force microscopy (AFM), and decidual functionality with a blastocyst-like spheroid implantation assay (using Swan71 cells). Decidualization induced a significant decrease in cellular stiffness (Young's modulus), consistent with a more permissive phenotype for embryo implantation. In contrast, exacerbated ERS -induced prior to decidualization- disrupted the balance between mature and senescent decidual cells and prevented this biomechanical softening, restoring stiffness to levels comparable to those on non-decidualized cells. Functionally, these alterations impaired trophoblast adhesion and expansion in vitro. Finally, to provide a physiologically relevant view of how decidualization operates in vivo, we studied endometrial samples from fertile women (N = 13) and from women with recurrent implantation failure (RIF, N = 11). These patients exhibited reduced expression of key decidualization and senescence markers evaluated by qPCR, similar to our results with exacerbated ERS, supporting the clinical relevance of our findings. Together, our results demonstrate that successful decidualization requires tight coordination between ERS, cellular senescence, and biomechanical remodeling. Disruption of this integrated program leads to a mechanically non-permissive endometrium, providing a novel mechanistic framework for implantation failure.