Search Results (967)

Fasciolosis, caused by the liver fluke Fasciola gigantica, remains a major parasitic disease affecting livestock in tropical regions and results in substantial economic losses. Although anthelmintic drugs are widely used for disease control, increasing reports of drug resistance highlight the need for alternative strategies such as vaccination. In this study, a recombinant digestive protein-based chimeric antigen (rFgCHI-DP) composed of three F. gigantica antigens—cathepsin L1 (FgCL1), cathepsin B1 (FgCB1), and saposin-like protein 2 (FgSAP2)—was designed and expressed in Escherichia coli. The mature regions of these proteins were sequentially linked to form a single chimeric construct. The recombinant protein was successfully expressed and purified under denaturing conditions, producing a protein of approximately 62 kDa. To evaluate its immunogenicity, BALB/c mice were immunized with rFgCHI-DP formulated with Quil A adjuvant. Indirect ELISA revealed that immunization induced antigen-specific IgG responses. Antibody responses showed strong reactivity toward FgCL1 and FgCB1, whereas the response against FgSAP2 was comparatively lower. Western blot analysis further demonstrated that antibodies generated against rFgCHI-DP recognized native parasite antigens. Immunolocalization also revealed that the anti-rFgCHI-DP antibodies could detect targeted antigens in the cecal epithelium of the parasite. These findings indicate that the adult-stage chimeric protein rFgCHI-DP is immunogenic in mice and capable of inducing specific antibody responses against F. gigantica. The results support the potential of rFgCHI-DP as a candidate antigen for future fasciolosis vaccine development. Full article

Mounting acaricide resistance in Tetranychus mexicanus (McGregor) (Acari: Tetranychidae), among the most damaging phytophagous mites in tropical and subtropical crops, has intensified the search for botanical alternatives. An oil-in-water nanoemulsion of Thymus vulgaris essential oil (TVEO-NE) was developed and evaluated for lethal and sublethal effects on adult females of T. mexicanus. TVEO, composed mainly of thymol (45%) and p-cymene (37%), was formulated by low-energy emulsification yielding stable dispersions (~200 nm; PDI < 0.25; zeta potential of −22.2 mV). At 30.0 mg a.i./mL, TVEO-NE caused 68.3% corrected mortality at 72 h and suppressed fecundity by ~44–52%; vehicle controls exerted only moderate effects, identifying the essential oil as the primary bioactive driver. Morphological examination revealed collapse of female idiosomata and disruption of excretory pellet architecture, corroborating the bioassay data. Molecular docking against a cathepsin L homology model revealed that thymol and p-cymene interact exclusively via hydrophobic contacts and display substantially lower ChemPLP fitness scores than the reference cysteine protease inhibitor E64, indicating weak predicted binding affinity and arguing against enzyme inhibition as the primary mechanism. Taken together, bioassay, morphological, and docking are consistent with supporting membrane partitioning as a plausible primary mode of action, positioning TVEO-based nanoemulsions as promising botanical tools for T. mexicanus management. Full article

Cognitive frailty, characterized by the coexistence of physical frailty and cognitive impairment, has emerged as a major challenge in aging populations and is closely linked to sarcopenia, neurodegeneration, and chronic inflammation. Increasing evidence suggests that the gut microbiota acts as a central regulator of neuromuscular and neurocognitive aging through the integrated gut–brain–muscle axis. This review highlights how microbial dysbiosis, reduced short-chain fatty acid (SCFA) production, systemic endotoxemia, and altered microbial metabolites contribute to mitochondrial dysfunction, neuroinflammation, anabolic resistance, and impaired neuroplasticity. Key signaling mediators, including SCFAs, bile acids, tryptophan-derived metabolites, cytokines, and myokines such as irisin, brain-derived neurotrophic factor (BDNF), and cathepsin B, orchestrate bidirectional communication among the gut, skeletal muscle, and brain. We further discuss the role of exercise-induced microbiota remodeling and muscle endocrine signaling in promoting mitochondrial biogenesis and cognitive resilience. In addition, emerging translational strategies including probiotics, prebiotics, postbiotics, polyphenol-rich functional foods, marine bioactives, and precision nutrition are explored as potential interventions targeting this axis. Collectively, the gut–brain–muscle axis provides a novel systems biology framework for understanding cognitive frailty and developing integrated therapeutic strategies for healthy longevity. Full article

Background: Pycnodysostosis is a rare autosomal recessive skeletal disorder caused by biallelic pathogenic variants in CTSK, which encodes cathepsin K, a lysosomal cysteine protease required for osteoclast-mediated degradation of bone matrix. Case Report: We describe a girl with short stature, skeletal deformities, osteosclerosis, craniofacial features, clavicular dysplasia, and radiological evidence of fractures. Clinical exome sequencing identified two heterozygous CTSK variants, c.85T > C (p.Trp29Arg) and c.679A>T (p.Ile227Phe), both currently classified as variants of uncertain significance. Segregation analysis showed that the variants were inherited in trans. Computational modeling and in silico prediction tools supported a possible deleterious effect on cathepsin K structure or function. Serum cathepsin K was higher in the patient than in two age-matched controls; this result is reported as an exploratory observation only. Increased serum cathepsin K may reflect altered expression, secretion, clearance, or accumulation of dysfunctional protein, but cannot be interpreted as proof of compensatory upregulation. Conclusions: The patient’s clinical and radiographic features, the biallelic trans configuration of the CTSK variants, their rarity in population databases, and computational predictions support p.Trp29Arg and p.Ile227Phe as strong candidate disease-associated variants. Functional studies are required to confirm their effect on cathepsin K expression, maturation, and enzymatic activity. Full article

Cathepsin C (CTSC), also known as dipeptidyl peptidase I, is an upstream activator of serine protease networks that may promote metastatic progression through inflammatory amplification and microenvironmental remodeling. Increasing evidence suggests that CTSC contributes to cancer progression not simply as an overexpressed lysosomal protease, but as a context-dependent regulator of metastatic traits. This review summarizes the structure, maturation, and biological functions of CTSC, with emphasis on its protease-activating capacity and its links to tumor-associated inflammation. Current evidence connecting CTSC to epithelial–mesenchymal transition, extracellular matrix remodeling, neutrophil extracellular trap formation, and immune microenvironment reprogramming is then synthesized across hepatocellular carcinoma, renal cell carcinoma, breast cancer, colorectal cancer, non-small-cell lung cancer, and glioma. Available data most strongly support a pro-metastatic role for CTSC in breast cancer and colorectal cancer, whereas evidence in several other malignancies remains predominantly preclinical and mechanistically incomplete. Importantly, CTSC is better viewed as a targetable protease network hub than as a universal pan-cancer metastatic driver. The biomarker potential and therapeutic relevance of CTSC are also evaluated, with particular attention to the opportunities and limitations of current DPP-1/CTSC inhibitors and the need for tumor-specific translational strategies. Overall, CTSC represents a promising but still incompletely validated target in oncology, and future work should prioritize tissue-specific dependency, biomarker qualification, and rational combination approaches. Full article

This study evaluated the effects of deheading and intestinal removal on protein degradation and quality changes in chilled Litopenaeus vannamei. The results showed that shrimp subjected to heads removed (HR) and both heads and intestines removed (HIR) maintained better muscle integrity and sensory characteristics compared with intact (CK) and intestines removed (IR) shrimp. Furthermore, the HR and HIR treatments significantly inhibited the accumulation of total volatile basic nitrogen, trichloroacetic acid-soluble peptides, and bitter free amino acids (including His, Lys, Leu, Val, and Tyr), while maintaining consistently low activities of trypsin, cathepsin B, cathepsins B+L, and cathepsin D in the muscle throughout storage. Additionally, intrinsic fluorescence spectroscopy, SDS-PAGE, and microstructural analyses revealed that HR and HIR treatments significantly delayed muscle protein degradation and effectively preserved the structural integrity of muscle tissue. These findings suggest that quality deterioration of shrimp during chilled storage may be largely associated with the migration of endogenous proteases from the hepatopancreas in the cephalothorax into the muscle tissue. Full article

Background/Objectives: Alzheimer’s disease (AD) is characterized by beta-amyloid (Aβ) plaque deposition, which impairs several cellular processes, including autophagy. Considering the multifactorial nature of AD, the development of therapies acting on alternative molecular targets is necessary. In this study, we evaluated the neuroprotective effect of a molecule from the hydrozoan Eudendrium carneum and investigated its impact on autophagy-related pathways. Methods: The secretion of E. carneum was fractionated by RP-HPLC according to its neuroprotective activity in SH-SY5Y cells exposed to oAβ42, evaluated using LDH and MTT assays. The purified molecule (named EC5), characterized by mass spectrometry, was evaluated regarding in silico toxicity and calcium dynamics. Neuronal lysosomal morphology was assessed using the LysoTracker probe, and cathepsin D activity was determined using a synthetic substrate. The expression of autophagy-related proteins (mTOR, LAMP-1, and LC3B) was evaluated by dot blotting, and amyloid plaque clearance was quantified using Thioflavin-T staining. Results: The steroid glycoside putatively identified as Sarmentoside B (EC5) exhibited neuroprotective effects and showed no toxicity or alterations in neuronal calcium or sodium channel dynamics. EC5 restored lysosomal morphology and cathepsin D activity, reversing the impairment induced by oAβ42. Furthermore, EC5 reduced mTOR expression, and this interaction was supported by molecular docking analysis. Lysosomal restoration promoted the clearance of oAβ42 aggregates, as evidenced by Thioflavin-T staining, resulting in reduced neuronal death. Conclusions: EC5, putatively identified as Sarmentoside B, exerts neuroprotective effects against oAβ42-induced toxicity by promoting autophagy-related amyloid clearance, highlighting its therapeutic potential for AD. Full article

Cathepsin Z/X (Cat Z/X) is a distinct member of the cysteine cathepsin family, known for its distinctive structural and functional properties, such as strict carboxypeptidase activity and integrin-binding motifs. These features set Cat Z/X apart from other cysteine proteases and underlie its involvement in diverse physiological and pathological processes, including immune regulation, cell signaling, and extracellular matrix remodeling. Dysregulated Cat Z/X expression and activity have been associated with various diseases, including cancer, neurodegenerative disorders, and metabolic conditions. This review summarizes current knowledge on Cat Z/X, focusing on its structural characteristics, biological functions, and roles in disease pathogenesis, particularly in malignancies, neuroinflammation, and metabolic disorders. It also explores natural and synthetic Cat Z/X inhibitors and their potential for therapeutic development. Despite growing research interest, the precise molecular mechanisms and context-specific functions of Cat Z/X are not yet fully understood. Further research is required to elucidate its regulatory networks, refine detection methods, and develop selective modulators targeting its proteolytic and non-proteolytic activities. A deeper understanding of Cat Z/X biology could pave the way for its application as a diagnostic biomarker and therapeutic target in numerous diseases. Full article

Cathepsin C (CTSC) is a major lysosomal cysteine protease characterized by its involvement in multiple essential pathological processes associated with various viral infections and pathogenesis, such as influenza virus and coronavirus. However, the antiviral spectrum of CTSC and the molecular mechanisms underlying its activity remain to be fully elucidated. In this study, we demonstrate that CTSC significantly inhibits the infection of influenza A virus (IAV) H1N1 both in vitro and in vivo. Mechanistically, the antiviral function of CTSC is associated with attenuation of the PI3K-AKT signaling pathway, thereby inducing cell apoptosis and reducing inflammation, which ultimately limits the virus’s ability to hijack host resources. Taken together, our findings highlight the crucial role of CTSC in defense against H1N1 by targeting PI3K-AKT pathway and suggest a prospective antiviral target against the infection of H1N1. Full article

Post-acute sequelae of SARS-CoV-2 infection (PASC) extend well beyond the acute respiratory phase, with accumulating virological evidence that SARS-CoV-2 RNA, viral antigens, and proteolytic fragments may persist in cardiovascular and other extrapulmonary tissues, although the extent to which such detection represents replication-competent reservoirs versus residual viral material with uncertain pathological relevance remains under active investigation. Sudden cardiac death (SCD) and fatal pulmonary thromboembolism (PTE) have emerged as forensically and epidemiologically significant outcomes in individuals with prior infection, situated at the intersection of microbiology, public health, and forensic medicine. To synthesize current evidence on the virological mechanisms by which SARS-CoV-2 may contribute to post-acute sudden cardiac death (SCD) and pulmonary thromboembolism (PTE), the population-level epidemiology of these outcomes, and their implications for public health surveillance and forensic practice, we conducted a narrative review of PubMed (MEDLINE), Scopus, and Web of Science Core Collection. The search covered publications from January 2020 to December 2025 and focused on SARS-CoV-2 cellular tropism and tissue persistence, immune-mediated and thromboinflammatory mechanisms, excess cardiovascular and thromboembolic mortality, and autopsy-based pathological findings. After de-duplication of 1837 initially identified records (412 duplicates removed) and screening of 1425 unique records, 78 studies were retained for final synthesis based on virological, epidemiological, and forensic relevance. SARS-CoV-2 enters cardiomyocytes, pericytes, and vascular endothelial cells through ACE2-dependent mechanisms, with cathepsin L compensating for the limited cardiac expression of TMPRSS2. Viral RNA and antigen have been detected in cardiovascular and other extrapulmonary tissues months after symptom onset in selected autopsy series, although persistent detection of viral components does not necessarily indicate ongoing productive infection or direct tissue injury. Endothelial dysfunction, neutrophil extracellular trap (NET) formation, complement activation, and persistent thromboinflammation have been proposed as plausible mechanistic substrates for arrhythmogenic remodelling and thromboembolic events, although definitive causal pathways remain incompletely understood. Population-based studies document persistent excess cardiovascular mortality across multiple jurisdictions, with hazard ratios for pulmonary embolism remaining elevated months after acute infection, particularly in unvaccinated individuals. Autopsy series identify mixed pathological patterns including focal lymphocytic infiltrates, microvascular thrombosis, contraction-band necrosis, and cardiomyocyte vacuolation, although fulminant lymphocytic myocarditis fulfilling Dallas criteria remains uncommon. A microbiology-informed framework uniting tissue-based viral detection, standardized cardiac and pulmonary sampling protocols, and prospective post-mortem registries is needed to better characterize the potential contribution of SARS-CoV-2 to post-acute cardiovascular mortality and to support cause-of-death certification, public health surveillance, and medicolegal practice in the post-pandemic era. Many of the proposed mechanisms remain under active investigation, and definitive causal relationships between viral persistence and adverse cardiovascular outcomes have not yet been conclusively established. Full article

Pancreatic cancer remains one of the most lethal malignancies worldwide, with pancreatic ductal adenocarcinoma accounting for the vast majority of cases and characterized by extensive desmoplasia, immune exclusion, and resistance to systemic therapies. Increasing evidence implicates lysosomal cathepsins as important regulators of these defining features of pancreatic tumor biology. Cathepsin-dependent proteolysis and lysosome-associated signaling pathways contribute to extracellular matrix remodeling, regulate immune cell trafficking, and influence antigen processing and presentation. Beyond their classical degradative functions, cathepsins participate in stress-adaptive cellular programs linked to autophagy, metabolic regulation, and proteostasis, supporting tumor cell survival under hypoxic, nutrient-limited, and therapy-induced stress conditions. Within the tumor microenvironment, dysregulated cathepsin activity promotes immune evasion by reshaping cytokine networks, impairing effective antigen presentation, and reinforcing physical and functional barriers to cytotoxic T-cell infiltration. Collectively, these mechanisms position the lysosome–cathepsin system as a central regulator of proteolytic remodeling, immune exclusion, and adaptive therapy resistance in pancreatic cancer, highlighting its potential relevance for emerging combinatorial therapeutic strategies. Full article

Osteoporosis arises from disrupted bone remodeling, and growing evidence shows that gut microbiota and their metabolites have a major influence on skeletal health through the gut-bone and gut–brain–bone axes. In this systematic review, we synthesize findings from 932 studies to identify key microbial taxa, metabolites, and signaling pathways that modulate osteoblast and osteoclast activities. Short-chain fatty acids (SCFA), tryptophan-derived metabolites, and β-D-glucuronidase-related estrogen regulation emerge as central microbial mechanisms affecting bone formation and resorption. By integrating these data with the Phylobone extracellular matrix proteins database, we highlight Osteopontin and Cathepsin K as important downstream mediators linking microbial signals to bone matrix turnover. Probiotic strains (particularly Lactobacillus rhamnosus GG and L. reuteri) show potential to improve bone health through metabolic, immune, and endocrine pathways. Together, these findings outline a mechanistic framework connecting gut function to skeletal biology and identify promising microbiome-based targets for osteoporosis interventions. Full article

Alveolar echinococcosis is a life-threatening zoonotic parasitic disease caused by infection of Echinococcus multilocularis larvae. To survive within the host’s immune milieu, E. multilocularis has evolved sophisticated immune evasion strategies, including the expression of immunomodulatory proteins that regulate the host immune response. Our previous studies have demonstrated that E. multilocularis calreticulin (EmCRT) possessed strong binding ability to human complement component C1q to inhibit C1q-initiated complement activation and biological functions. To further elucidate the mechanism by which EmCRT mediates C1q inactivation and immune evasion, the precise C1q-binding site on EmCRT was identified and analyzed in this study through expression of overlapping fragments and synthesis of overlapping peptides covering the identified functional fragment. The fragment expression and functional assay narrowed down the C1q-binding site to the EmCRT-S1 fragment located between amino acids 140 and 204 of EmCRT. The precise binding site was further pinpointed to the P5 peptide (EmCRT160–174 aa) by testing the synthetic peptides covering this region. The binding of peptide P5 to C1q markedly suppressed the activation of the C1q-mediated classical complement pathway and C1q-induced neutrophil chemotaxis, production of reactive oxygen species, cathepsin G, and myeloperoxidase. These findings suggest that the C1q-binding P5 peptide of EmCRT may serve as a potential target for the development of vaccines against echinococcosis or therapeutic drugs for complement-associated inflammatory or autoimmune diseases. Full article

Rett syndrome is a severe neurodevelopmental disorder caused predominantly by loss-of-function mutations in the X-linked gene MECP2. In addition to a vast array of neurological and physiological impairments, patients also frequently develop severe osteopenia with increased fracture risk; however, the mechanisms underlying these skeletal defects are not completely understood. Previous work in Mecp2-null mouse models has suggested that osteopenia is mainly due to impaired osteoblast function and reduced bone formation. Here, we examined bone mass, microarchitecture, and remodeling parameters in a Mecp2-null mouse model during postnatal development, with a particular focus on osteoclast involvement. Microcomputed tomography and histomorphometric analyses showed reduced bone mineral density and trabecular bone volume, which are associated with increased trabecular separation and cortical thinning. These structural alterations were accompanied by increased osteoclast number per bone surface, elevated urinary deoxypyridinoline, and higher expression of osteoclast-associated genes, including Cathepsin K. Furthermore, gene expression analysis revealed an age-dependent shift in bone remodeling. At postnatal day 35, mutant mice showed reduced expression of Dlx5 and Dlx6, consistent with low bone turnover. By postnatal day 55, Rankl and Cathepsin K were markedly upregulated, suggesting an increase in osteoclast resorptive activity, while key osteoblast markers and the RANKL/OPG ratio did not change significantly. A potential cell-autonomous contribution of Mecp2 to osteoclast maturation is also suggested by the analysis of public transcriptomic datasets on human osteoclast differentiation. Together, our findings identify increased osteoclast activity as a significant contributor to Rett-associated osteopenia and suggest that skeletal pathology in Mecp2 deficiency progresses from an early low-turnover state to a later phase of increased osteoclast resorption. Full article

Background: Estrogen deficiency and glucocorticoid exposure are major contributors to osteoporosis. Although menaquinone-7 (MK-7) exhibits osteoprotective effects, whether low-dose supplementation is comparable to high-dose treatment remains unclear. Methods: Female Sprague–Dawley rats were assigned to sham control (SC), ovariectomy plus dexamethasone (OVX+Dex), and OVX+Dex treated with low-dose MK-7 (100 μg/kg) or high-dose MK-7 (20 mg/kg). Bone microarchitecture, histopathology, and serum bone turnover markers were evaluated. Results: OVX+Dex induced marked deterioration of trabecular bone microarchitecture, characterized by reduced bone volume and structural disruption. These changes were accompanied by increased osteoclast activity (cathepsin K), decreased osteogenic and extracellular matrix–related markers (cbfa-1, osteonectin, and biglycan), and downregulation of osteoprotegerin, indicating a pronounced imbalance in bone remodeling. Serum analysis further revealed reduced estradiol levels and alterations in circulating bone turnover markers, consistent with a dysregulated high-turnover state. Both low- and high-dose MK-7 significantly improved bone microarchitecture, restored remodeling-related protein expression, and partially normalized serum calcium-regulating hormones and bone turnover markers (all p < 0.05), with no significant differences observed between doses. Conclusions: MK-7 attenuates osteoporosis by restoring the balance between bone resorption and formation. Notably, low-dose MK-7 provides protective effects comparable to high-dose treatment, supporting its potential clinical utility. Full article