Purpose: Workers occupationally exposed to fuel vapors are at risk of contamination by heavy metals such as lead and cadmium. This study aimed to quantify blood levels of lead and cadmium and evaluate associated biochemical, hormonal, and oxidative stress alterations among fuel station workers. Methods: This cross-sectional study recruited 66 healthy males, comprising 33 workers with at least 2 years of direct fuel exposure and 33 non-exposed controls. Blood lead and cadmium were quantified using Flame Atomic Absorption Spectrophotometry (AAS). Biochemical markers, reproductive hormones, and oxidative stress indicators were analyzed. Statistical analyses were performed using independent t-tests to identify significant differences between groups, and Pearson’s correlation test to assess associations. Results: Mean blood lead (43.4±5.4 µg/dL vs. 23.6±1.6 µg/dL; P<0.05) and cadmium levels (10.1±1.2 µg/dL vs. 5.5±0.4 µg/L; P<0.05) were significantly higher in exposed workers. Biochemical markers were elevated including ALT (38.76±3.3 U/L vs. 24.39±3.6 U/L; P<0.05), AST (29.91±3.4 U/L vs. 16.55±4.0 U/L; P<0.05), ALP (82.82±12.4 U/L vs. 42.67±9.5 U/L; P<0.05), BUN (19.52±3.1 v mg/dL s. 9.82±2.0 mg/dL), and Creatinine (1.13±0.1 mg/dL vs. 0.72±0.1 mg/dL; P<0.05) in exposed group. Oxidative stress was evident with higher MDA (2.86±0.6 nmol/mL vs. 0.84±0.2 nmol/mL; P<0.05) and lower SOD and GSH (P<0.05). Testosterone decreased (3.77±0.9 ng/mL vs. 4.98±0.9 ng/mL; P<0.05) while FSH increased (P<0.05). Conclusion: Occupational exposure to lead and cadmium suggests adverse hepatic, renal, hormonal, and oxidative stress changes among fuel station workers. Regular monitoring of biochemical and hormonal markers is strongly recommended, along with preventive exposure-control measures.

Intranasal delivery is a method of administering medications through the nasal cavity. It offers several advantages, such as rapid absorption, bypassing first-pass metabolism, direct nose-to-brain transport and localized effects. These benefits make it a promising approach for drug delivery in Parkinson's disease, a progressive neurological disorder characterized by the degeneration of nerve cells in the brain. This review evaluates the efficacy and safety of intranasal delivery for Parkinson’s disease treatment. Several studies on intranasal apomorphine reported rapid clinical response, improved UPDRS motor scores, tapping scores, and median Webster’s scores, suggesting its effectiveness as a rescue therapy during "off" states. Intranasal recombinant erythropoietin was well tolerated and showed cognitive benefits. intranasal glutathione was safe and showed better bioavailability. Intranasal insulin improved cognitive performance without hypoglycemia, indicating a localized effect. Intranasal cholecystokinin and ipratropium bromide did not show significant benefits. Intranasal desmopressin is a safe and effective medication for nocturnal polyuria in Parkinson disease. Intranasal transplantation of neural stem cells is safe and is associated with functional improvement. Finally, Rivastigmine nasal spray offered better bioavailability and fewer side effects compared with conventional forms. The most common adverse effect was mild transient nasal or throat irritation. This review highlights the potential applications, efficacy, and side effects of various intranasal medications for Parkinson’s disease and proposes using new interventions for future studies. Generally benefits of nasal administration of Parkinson’s treatment include localized effects, fewer side effects, faster onset of action, improved bioavailability, and enhanced therapeutic effectiveness.

Purpose: Bowel dysfunction frequently occurs in colorectal cancer (CRC) patients following sphincter-preserving surgeries. This review systematically evaluated the evidence on pharmacological therapies for this complication. Methods: A systematic search was conducted in PubMed, Web of Science, and Scopus in November 2024. Experimental or quasi-experimental studies examining the effects of conventional pharmacological therapies and herbal medicine on stable CRC patients with post-surgical bowel dysfunction were included. Results: Among 8,989 retrieved records, eight studies were eligible. These investigated the effects of serotonin type 3 receptor antagonists (n=3), herbal medicines (n=2, specifically Daikenchuto and modified Baizhu Shaoyao San), diazepam (n=1), Botulinum A toxin injection (n=1), and topical phenylephrine (n=1). Except for phenylephrine, interventions showed varying improvements in stool frequency, incontinence, urgency, or quality of life. Most of the included studies exhibited a high risk of bias. Conclusion: Some interventions appear promising; however, the current evidence is insufficient to guide clinical practice. This review highlights a significant evidence gap and underscores the urgent need for large-scale, rigorous randomized controlled trials to establish definitive therapeutic strategies for this debilitating condition.

Purpose: Nanobodies possess unique properties that make them promising as tumor targeting agents. Prostate-specific membrane antigen (PSMA), overexpressed in prostate cancer, can be an excellent target for prostate cancer diagnosis. This study aimed to express and purify an anti-PSMA nanobody (PSMA-Nb) and assess its potential for detecting PSMA antigen in prostate cancer through immunohistochemistry (IHC). Methods: The PSMA-Nb gene was subcloned into pET-28a and expressed in E. coli Rosetta (DE3) and Rosetta-gami2 under varying IPTG/temperature/time conditions (0.5/1.0/1.5 mM; 16/30/37 °C; 4/16 h). The soluble and inclusion-body fractions were analyzed, and PSMA-Nb was purified via native Ni-NTA, confirmed by SDS-PAGE and anti-c-Myc Western blot. Binding was validated by ELISA against recombinant PSMA and by flow cytometry on LNCaP (PSMA+) and DU145 (PSMA-). For tissue studies, FFPE IHC quantified staining as fractional fluorescent area per mm². Results: PSMA-Nb (~27 kDa) was enriched in E. coli inclusion bodies. A factorial screen identified Rosetta (DE3) with 1 mM IPTG at 37 °C for 16 h as the highest-expressing condition; resulting in a yield of approximately 84 mg/L. ELISA showed dose-dependent binding to recombinant PSMA, and flow cytometry confirmed antigen selectivity (LNCaP 68.5% vs. DU145 2.35%). IHC showed higher PSMA levels in tumor vs. normal tissue with both reagents (PSMA-Nb: 21.61 ± 2.89 vs. 5.82 ± 1.80; commercial antibody: 20.55 ± 3.80 vs. 5.50 ± 2.14; P<0.0001), with no difference between reagents (P=0.9624), supporting analytical validity. Conclusion: The superior features of nanobodies support antibody-based diagnostics in solid tumors. Purified PSMA-Nb detected PSMA on cancer cells and FFPE tissues, indicating a promising tool for prostate cancer diagnosis.

Purpose: Microglial cells play a crucial role in responding to brain hypoxia. This study aimed to evaluate the effect of RNA-binding proteins (RBPs) on the resistance of microglial cells to hypoxia. Methods: Newborn rats were subjected to hypoxia under four conditions: hypoxia (H), one week after hypoxia induction (H1), control (C), and control one week after hypoxia induction (C1). Microglial cells were isolated and cultured, and exosomes were extracted from brain samples of healthy newborn rats of C1 group. RBPs were extracted from the aforementioned groups and transferred into the microglial cells using exosomes from the C1 group. Cell viability, expression of specific RBP genes, and innate immune factors were evaluated in the studied groups. Additionally, exosomes containing RBPs were injected into the hypoxic rats to investigate behavioral changes in-vivo. Results: The treatment of microglial cells with C1 exosomes elevated the viability rate. The RBP-H proteins significantly elevated the expression of the CPE, HIF-1α, PDI, and VEGF-A genes. Improvements in anti-protease activity, along with decreases in lysozyme and myeloperoxidase activity, were observed in hypoxic microglial cells following treatment with RBP-H and exosomes containing RBP-H. In vivo evaluations revealed that the hypoxic group treated with exosome loading with RBP-H exhibited significant improvements in recognition and balance maintenance. Conclusion: The RBPs may be considered a promising option for further studies in the treatment of brain disorders resulting from hypoxia.

Purpose Liver fibrosis, characterized by excessive extracellular matrix accumulation, reflects a maladaptive repair response to persistent hepatic injury. Recent studies implicate cellular senescence and immune checkpoint dysregulation as pivotal drivers of fibrogenesis, yet these pathways remain underutilized in therapeutic development. This study evaluates the anti-fibrotic efficacy of metformin and dapagliflozin, two metabolic modulators, in a thioacetamide (TAA)-induced rat model, emphasizing their impact on senescence and immune regulation. Methods Male albino rats (N=6/group) were assigned to five groups: control, TAA (200 mg/kg, i.p., thrice weekly for 4 weeks), TAA + metformin (300 mg/kg/day), TAA + dapagliflozin (1 mg/kg/day), and TAA + combination therapy. Liver tissues underwent histopathological examination and SMAD-3 mRNA quantification via qRT-PCR. Protein levels of TGF-β1, PD-1, p16, NF-κB, α-SMA, fibronectin, collagen-I, and sirtuin-1 were assessed, alongside serum oxidative stress markers (MDA, SOD) and liver enzymes (ALT, AST). Results All treatments significantly reduced fibrosis, collagen deposition and improved liver architecture. Mechanistically, both drugs suppressed fibrotic and senescence markers, downregulated PD-1, enhanced sirtuin-1, and mitigated oxidative stress. Notably, combination therapy yielded synergistic anti-fibrotic effects. Conclusions These findings highlight a dual-pathway therapeutic strategy targeting senescence and immune imbalance, with relevance to metabolic liver disease.

Purpose: More than thirty human proteins have natural propensity to misfold and amyloid fibril formation that are important in the initiation and development of neurodegenerative disease. Therefore, preventing or reversing amyloid aggregation by using drugs or plant-based small molecules such as coumarin compounds could be useful. This study aimed to investigate the anti-amyloidogenic potential of psoralen and seselin, two types of coumarin compounds, on hen egg white lysozyme (HEWL) as a model system. Method: ThioflavinT (ThT), Congo red and ANS fluorescence, electron microscopy and circular dichroism were used to fibrillogenesis assay and structural analysis in the presence and absence of the compounds. Interaction of HEWL and coumarins evaluated by using surface plasmon resonance (SPR) and molecular docking and simulation. Results: The results indicated the ThT and ANS fluorescence intensities decreased in the presence of psoralen and seselin in a dose-dependent dependent manner, suggesting a strong inhibitory effect of compounds on HEWL fibril formation. The results confirmed coumarins could destabilize the pre-formed fibrils. Furthermore, Fluorescence analysis confirmed that coumarin interaction induces conformational changes in HEWL, evidenced by formation of non-fluorescent complexes and altered microenvironments around Tyr and Trp residues. CD spectrum revealed that coumarins can inhibit the α-helix to β-sheet exchange. SPR results showed psoralen could bind to HEWL more tightly. Conclusion: In agreement with experimental results, the molecular docking studies confirmed the conformational changes of HEWL upon interaction with psoralen and seselin. This study adds to the body of knowledge about rational drug design against the amyloidogenesis process.

Colorectal cancer (CRC) is one of the most prevalent cancers in the world, which affects developed countries the most. Many pathways and mechanisms were attributed as the cause of CRC, and one of the targets of interest is the long non-coding ribonucleic acid (lncRNA), growth arrest specific 5 (GAS5). GAS5 have been observed to play an important role in many other cancers, and CRC is not an exception. This paper aims to understand the role and mechanisms played by GAS5 in relation to CRC progression. It is found that GAS5 have a complex role, and a major one being its competitive endogenous nature that could downregulate multiple microRNAs such as miR-485-5p, miR-137, miR-26b, miR-21, miR34a, miR-182-5p, miR-128-30, and miR-221, which have implications in tumour growth and suppression. It is also observed to be able to interact with proteins directly, such as the Yes-Associated Protein (YAP). Both clinical and laboratory evidence support the fact that in the context of CRC, GAS5 overexpression is a protective factor, while its underexpression is related to worse prognosis and survival rate. This has opened up its potential as a prognostic biomarker, as well as a therapeutic target to treat multiple cancers, including CRC. However, more research is still required to answer the knowledge gap. In conclusion, GAS5 plays multiple roles and is an important player in cancer regulation, including CRC, and it holds good potential to be a biomarker and a therapeutic target.