Cellular Physiology and Biochemistry最新文献

Parasites represent a diverse and widely distributed group of pathogens that cause diseases with significant global health implications. The interaction between parasite and host is characterized by a high degree of complexity, with both parties continuously adapting to changes in the other. The successful host invasion is largely attributable to the evasion strategies employed by parasites to ensure their survival in immunocompetent individuals. In turn, the host's defense mechanisms utilize a variety of structures and processes, ranging from primary barriers to the most sophisticated ones, to counter the parasite attack. Acting as an early line of defense, the immune system includes a variety of cell types that are capable of recognizing, destroying, and eliminating infectious agents. Undoubtedly, the orchestration of first-line innate immune responses but also adaptive immunity processes during infection depends to a large extent on the involvement of tissue-resident mast cells (MCs). MCs are capable of supporting immune reactions to parasites through a broad spectrum of processes, including degranulation, synthesis and release of cytokines/chemokines and other mediators, and the generation of reactive oxygen species (ROS). They may also be involved in immune cell recruitment, phagocytosis, and the provision of extracellular DNA traps. Despite the well documented association of MCs with antibacterial and antiviral defense, their role in host protection against parasites remains incompletely identified. This article provides an overview of the engagement of MCs in host defense mechanisms developed during parasitic infections. Furthermore, it considers the impact of parasites or parasite-derived molecules on the various aspects of MC activity.

Background/aims: Drug addiction is a neuropsychiatric disorder characterised by compulsive drug-seeking behaviour notwithstanding adverse consequences. This work seeks to address a deficiency in the literature by comparing drug-addicted and non-addicted individuals within an Iraqi population through the analysis of a 1000-base pair variable number of tandem repeats (VNTRs) polymorphism of the dopamine receptor gene DRD4. The association of this novel polymorphism with drug addiction has not yet been examined.

Methods: A total of 270 people were registered between May 2022 and June 2023. Of these, 180 had drug addictions and 90 were healthy controls. DNA was extracted from the participants' blood samples. Restriction Fragment Length Polymorphism was used to investigate genetic polymorphisms in the DRD4 and VNTR genes to identify differences.

Results: The genotype frequencies differed markedly between the control group (GC, 3% frequency) and the patient group (GC, 37% frequency). The control group had more of the genotype that was more common among addicts. The C allele was present in 60% of the patients but in only 1% of the controls. The results showed that the CC genotype is more common in the patient group than in the control group. A comparison of repetitions between the control and patient groups was made based on the distribution of genotypes of SNP rs747302. Patients with the GG genotype had an average of 17 repetitions, whereas those with the GC genotype had 18, and those with the CC genotype had 18.3. The results showed that people in the CC genotype group had a lot more repetitions.

Conclusion: The results of our study indicated that the CC, GC, and VNTR genotypes significantly contribute to heroin addiction risk in Iraqis.

Background/aims: The ubiquitin-like protein ISG15 and its covalent conjugation to substrates (ISGylation) represent a critical interferon (IFN)-induced antiviral mechanism. USP18 is an ISG15-specific isopeptidase and a key negative regulator of type I IFN signaling. While inactivation of USP18's catalytic activity enhances ISGylation and promotes viral resistance, its role in modulating inflammation and cardiac function during CVB3-induced myocarditis remains unclear. This study aimed to determine whether selective inactivation of USP18 isopeptidase activity influences the inflammatory and functional course of viral myocarditis.

Methods: Usp18 C61A/C61A knock-in mice, which lack USP18 isopeptidase activity but retain IFN regulatory function, were used on both C57BL/6 and A/J backgrounds. Mice were infected with the cardiotropic CVB3-Nancy strain, and disease progression was assessed through virological, histological, immunological, and echocardiographic analyses. Immune cell infiltration was quantified by flow cytometry, and ISGylation was assessed by immunoblotting.

Results: Despite enhanced ISGylation, Usp18 C61A/C61A mice did not exhibit altered cardiac viral titers or inflammation compared to wild-type controls. Histological scores and immune cell composition in the heart were similar between genotypes in both C57BL/6 and A/J backgrounds. Echocardiography confirmed functional impairment following CVB3 infection but revealed no significant genotype-dependent differences in cardiac performance. Inflammatory cytokine expression was largely unaffected by enhanced ISGylation, with only minor differences observed.

Conclusion: While ISGylation is critical for antiviral protection in CVB3 infection, selective inactivation of USP18 isopeptidase activity does not mitigate myocardial inflammation or dysfunction during established CVB3 myocarditis. These findings suggest that therapeutic enhancement of ISGylation alone may be insufficient to control inflammation-driven cardiac damage in this model.

Migrasomes are newly discovered, migration-dependent organelles that mediate the release of cellular contents into the extracellular environment through a process known as migracytosis. Since their identification in 2014, growing evidence has highlighted their critical roles in intercellular communication, organ development, mitochondrial quality control, and disease pathogenesis. Migrasome biogenesis is a complex, multi-step process tightly regulated by lipid composition, tetraspanin-enriched microdomains, and molecular pathways involving sphingomyelin synthase 2, Rab35, and integrins. Unlike exosomes, migrasomes possess distinct structural and functional characteristics, which position them as novel organelles rather than classic extracellular vesicles. Recent studies have revealed their involvement in diverse pathological contexts, including kidney disease, cancer progression, proliferative vitreoretinopathy, viral infections, and myocardial infarction. Notably, migrasomes hold promise as diagnostic biomarkers, especially in early podocyte injury, and as therapeutic targets in oncology and regenerative medicine. This review summarizes the current understanding of migrasome biology, and their implications in health and disease, and explores emerging perspectives on harnessing migrasomes for diagnostic and therapeutic applications.

Macrophage Migration Inhibitory Factor (MIF) is a pleiotropic cytokine that acts as a central regulator of inflammation and immune responses across diverse organ systems. Functioning upstream in immune activation cascades, MIF influences macrophage polarization, T and B cell differentiation, and cytokine expression through CD74, CXCR2/4/7, and downstream signaling via NF-κB, ERK1/2, and PI3K/AKT pathways. This review provides a comprehensive analysis of MIF's mechanistic functions under both physiological and pathological conditions, highlighting its dual role as a protective mediator during acute stress and as a pro-inflammatory amplifier in chronic disease. MIF's involvement in autoimmune disorders, neurodegeneration, metabolic syndromes, infectious diseases, and oncogenesis is examined, with particular attention to its contribution to immune dysregulation, immune escape, and the shaping of inflammatory microenvironments. Its clinical relevance as a biomarker is underscored by associations between elevated serum levels, polymorphic variants such as the -173 G>C SNP, and disease susceptibility, progression, and therapeutic response. Advances in therapeutic strategies are also discussed, including the development of small-molecule inhibitors, MIF-2-specific antagonists, CD74-targeted therapies, and gene-based interventions. Taken together, emerging evidence positions MIF as both a diagnostic indicator and a therapeutic target, with its broad regulatory functions across immune, vascular, and metabolic pathways emphasizing its relevance in precision immunotherapy and its potential to serve as a strategic axis in the future of translational medicine.

Background/aims: Ubiquitin D (UBD), a member of the ubiquitin-like modifier (UBL) family, is significantly overexpressed in various cancers and is positively correlated with tumor progression. However, the role and underlying mechanisms of UBD in rheumatoid arthritis (RA) remain poorly understood. This study aimed to investigate the effects of UBD knockdown on the progression of RA.

Materials: We employed the type II collagen and incomplete Freund's adjuvant (CIA) rat model. A variety of analytical techniques were employed, including hematoxylin and eosin (H&E) staining, Safranin O and Fast Green staining, tartrate-resistant acid phosphatase (TRAP) staining, enzyme-linked immunosorbent assay (ELISA), and Western blot analysis, to elucidate the mechanisms involved.

Results: UBD knockdown correlated with diminished cartilage and bone erosion, reduced counts of TRAP-positive osteoclasts, and enhanced Safranin O staining of the cartilage. Additionally, the knockdown significantly reduced serum levels of PGE2, TNF-α, TIMP-1, IL-1β, MMP-9, and IL-6 in CIA rats. Furthermore, UBD knockdown markedly suppressed the expression levels of phosphorylated p38, TLR4, MyD88, and phosphorylated p65, suggesting a critical role in modulating inflammatory signaling pathways in RA.

Conclusion: Collectively, these results suggested that knockdown of UBD significantly alleviated arthritis progression in the CIA rat model, highlighting UBD as a potential therapeutic target and a promising prognostic biomarker for RA.

Background/aims: The quantification of amino acids in the dairy industry is necessary for quality control and for the formulation of functional foods. Thus, the development of enzymatic biosensors requires a detailed study of enzyme kinetics. Parameters such as KM and Vmax are necessary to optimize the sensitivity and specificity of the biosensor.

Methods: The enzyme immobilized on nylon and yucca bipolymer membranes was studied to evaluate possible interferences in the amperometric sensor.

Results: The sensor developed based on enzyme kinetics proved to be a reliable, sensitive, and low-cost alternative for determining lysine in dairy products. Its performance, comparable to HPLC, together with its low environmental impact, positions it as a useful tool for quality control in the food industry.

Conclusion: An enzymatic biosensor capable of quickly, accurately, and economically quantifying lysine in casein hydrolysates was developed. Its high sensitivity, enzymatic stability, and low environmental impact make it a viable and comparable alternative to HPLC for quality control in dairy products.

It is imperative to comprehend the multifactorial causes of male infertility and to identify effective treatment methods, to enhance male reproductive health, and to develop more personalised and effective therapeutic interventions. This review discusses the multifactorial aspects contributing to male infertility, focusing on oxidative stress (OS), sperm quality, gut microbiota, and the potential role of adaptogens. A comprehensive literature search was conducted across several major databases, including the Cochrane Library, Medline, Embase, SciSearch, PubMed, Web of Science, Scopus, and Google Scholar. The findings from the studies included in the databases highlight the significant role of oxidative stress in male infertility, with reactive oxygen species (ROS) contributing to sperm DNA fragmentation and impairment of spermatogenesis. The review further elucidates the influence of both endogenous and exogenous sources of ROS, including lifestyle factors and environmental exposures, on male reproductive health. Emerging research also highlights the involvement of key molecular pathways, such as Nrf2, AMPK/PGC-1α, and NF-κB, in regulating OS within the male reproductive system. Additionally, the review outlines the relationship between endothelial dysfunction, cardiovascular health, and male infertility, identifying OS as a common underlying factor. In addition to the OS, the gut microbiota has been identified as a pivotal factor in male fertility, influencing inflammation and hormonal regulation. This review underscores the potential merits of a synergistic strategy that integrates dietary interventions, antioxidants, gut microbiota modulation, and adaptogens to enhance fertility outcomes. Adaptogens, recognised for their capacity to assist the body in coping with stress and re-establishing equilibrium, may confer protective effects against OS and improve reproductive health. The review under discussion emphasises the importance of a holistic approach to male infertility, integrating molecular, clinical, and lifestyle factors to optimise reproductive health.