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.

Biomimetic Scaffold of Chitosan from Litopenaeus vannamei Shrimp Shells Incorporated with Collagen and Hydroxyapatite for Bone Tissue Regeneration

Purpose: Colorectal cancer (CRC) is a formidable global health challenge, ranking as the third most prevalent cancer. Conventional treatments like surgery, radiation, and chemotherapy are limited by adverse effects, driving the search for more effective alternatives.Methods: This study investigates the synergistic potential of co-delivering 5-fluorouracil (5-FU) and cannabidiol (CBD) using hyaluronic acid (HA)-decorated liposomes. While 5-FU is a cornerstone of CRC treatment, CBD offers promise as an anti-tumor agent. The HA-decorated liposomes enable potential targeted drug delivery to CD44 receptors, which are overexpressed in CRC, while minimizing systemic toxicity by reducing the concentrations of anticancer drugs required.Results: The liposomal formulation displays optimal physicochemical properties (a sub100nm size and an appropriate negative zeta potential) and acceptable encapsulation and loading efficiencies, ensuring effective drug release. In vitro studies demonstrate that the targeted liposomes have superior anticancer effects, inducing apoptosis (up to 59.1%), cell cycle arrest in the Sub-G1 and G0-G1 phases, reduction of cell viability to 6.98% in human colorectal adenocarcinoma (HT-29) cells, induction of oxidative stress, and inhibition of colony formation. Additionally, HepG2 (non-CD44-expressing) cells were used as a control to evaluate CD44-targeting efficiency. Gene expression analysis by real-time PCR indicates modulation of key genes associated with cell cycle progression and apoptosis.Conclusion: This multifaceted approach presents a promising strategy for CRC therapy, but requires additional optimization and rigorous in vivo investigations to facilitate successful clinical translation. In particular, optimization of drug-release kinetics and thorough in vivo validation are essential to advance this platform toward clinical application.

Background and Purpose: Furosemide (FUR) is a potent diuretic, practically water-insoluble drug and also known to exhibit polymorphic form I (most stable), and metastable form II and form III. FUR was crystallized using aqueous polymeric solution and the effect of crystallite properties on polymorphic transformation and dissolution was studied. Methods: FUR was crystallized using aqueous solution of HPMC, CMC, MC, or, PVA as non-solvent (FH, FC, FM, and FP respectively). Crystallite properties were analyzed using Scherrer and Williamson-Hall equation. Effect of crystal on drug dissolution were also studied. Results: FTIR study of FH and FM exhibited only two peaks (3342.99 and 3250.43 cm-1), considering form II, whereas, FP and FC presented three distinct peaks between (3397.95, 3348.78, and 3280.32 cm-1) corresponding to asymmetric sulfonamide-NH, secondary amine-NH, and symmetric sulfonamide-NH stretching respectively, confirming the presence of form-I. Further, XRD and DSC also established the polymorphic identity of the crystal forms. Crystallite size analysis using the Scherrer equation and Williamson-Hall plot revealed a significant reduction in the size of all crystal products compared to pure FUR, with an associated increase in dislocation density, suggesting enhanced structural imperfections. All prepared crystals demonstrated markedly improved dissolution profile relative to the pure drug. Furthermore, stability studies under accelerated condition (40°C/75%RH, 3 mo) confirmed the retention of respective polymorphic forms without any noticeable changes (FH and FM stayed in form II and FC and FP stayed in form I). Conclusion: Furosemide form I has been transformed to stable form II after crystallization in aqueous polymeric solution of HPMC and MC, and not by CMC and PVA. A comparative analysis was undertaken using Scherrer vs. Williamson-Hall equation. Improved dissolution was also witnessed with all the crystals.

Purpose: Effective inhaled drug delivery is essential for managing bronchial asthma and chronic obstructive pulmonary disease (COPD). This study compared the aerosolization efficiency of two different dry powder inhalers (DPIs), the Aerolizer and Revolizer, using a fixed formulation of formoterol fumarate.Methods: Aerodynamic particle size distribution was measured using a next-generation impactor (NGI), and delivered dose uniformity was assessed with a dosage unit sampling apparatus (DUSA), both at a fixed flow rate of 60 L/min. Drug content was quantified using a validated high-performance liquid chromatography (HPLC) method, and performance metrics were analyzed using CITDAS software. Data were averaged (mean±SD) and compared by statistical tests (e.g., ANOVA or t-tests), with P<0.05 indicating significance.Results: The Aerolizer achieved a fine particle dose (FPD) of 4.71 µg, which was 2.39 times higher than that of the Revolizer (1.97 µg). It also delivered approximately 20% greater overall dose and showed more consistent deposition in the NGI stages. While both devices demonstrated similar fine particle fractions (FPFS), the difference in FPD was primarily due to the higher emitted dose from the Aerolizer. The use of a fixed flow rate allowed direct comparison of device performance.Conclusion: These findings highlight the significant influence of device design on DPI performance, even when the formulation remains constant. The Aerolizer, a low-resistance inhaler, showed superior delivery efficiency than the Revolizer under standardized conditions. Future studies should include pressure-drop–adjusted or patient-simulated testing to better reflect clinical inhalation profiles and further explore how device mechanics influence drug delivery.

Antibiotic resistance, driven by bacterial adaptability through genetic mutations and horizontal gene transfer, poses a critical global health challenge. 1Bacteria employ diverse resistance mechanisms, including beta-lactamase production, altered penicillin-binding proteins (PBPs), reduced membrane permeability, and efflux pumps, which lead to multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. 2,3These mechanisms increase mortality, prolong hospital stays, and raise healthcare costs, highlighting the urgent need for innovative strategies to enhance antibiotic efficacy and curb resistance. 4 Amoxicillin, a broad-spectrum beta-lactam antibiotic, inhibits bacterial cell wall synthesis by targeting PBPs, resulting in osmotic instability and cell lysis. 5 It is effective against pathogens such as Streptococcus spp., Staphylococcus spp., Escherichia coli, and Haemophilus influenzae. 5However, resistance primarily through beta-lactamase enzymes that hydrolyze the beta-lactam ring, along with biofilms that limit antibiotic penetration compromises its effectiveness. 6,7 Combining amoxicillin with beta-lactamase inhibitors like clavulanic acid can partially restore its activity, yet novel adjuvants remain essential to overcome complex resistance mechanisms. 8Hypothesis: We propose that metformin, traditionally used for glucose regulation, may serve as an adjuvant to amoxicillin, enhancing its antibacterial efficacy and potentially reducing resistance development through metabolic restriction and immunomodulation.While metformin lacks direct antibacterial action, its effects on host metabolism and immune responses may create an unfavorable environment for bacterial survival, thereby complementing amoxicillin's bactericidal effect. Molecular Mechanisms of Metformin's Adjuvant Potential:Metformin activates AMP-activated protein kinase (AMPK), a central regulator of cellular energy homeostasis. 9AMPK activation shifts metabolism toward lipid oxidation and reduces glucose availability, particularly in inflamed tissues where bacteria exploit nutrientrich conditions. 10This metabolic restriction may stress bacterial energy production, increasing susceptibility to amoxicillin's cell wall-targeting effects. 11Additionally, metformin inhibits the mechanistic target of rapamycin How to cite

Purpose: Tumor hypoxia is a key barrier to successful delivery and activity of anti-cancer agents. To tackle this, we designed hypoxia-responsive Au-PEI-Azo-mPEG nanoparticles (NPs) denoted as APAP NPs for targeted delivery of hypoxia-activated prodrug (HAP), tirapazamine (TPZ) to hypoxic breast cancer cells.Methods: AuNPs were first synthesized. And then, were coated with polyethylene imine (PEI) by EDC-NHS chemistry. To realize NP biocompatibility and self-activating potential, a hypoxia-cleavable mPEG-AZO linker shell was coupled to the Au-PEI core. The hypoxia-responsible behavior of nanoparticles was analyzed under 21% O2 (normoxia) and 1% O2 (hypoxia) condition in 2D cell culture as well as MDA-MB-231 and MCF-7 spheroids as reliable biomimetics of tumor hypoxia.Results: APAP NPs elicited comparable cytotoxicity upon MDA-MB-231 cancer cells lowering TPZ IC50 to 7.46 µg/mL after 24 h. And were capable of enhanced ROS generation (P<0.001), and reduced mitochondrial membrane potential under hypoxia condition compared to the control (P<0.0001). Further, these NPs induced widespread apoptosis in both 2D and 3D cancer cell culture (P<0.0001), significantly reduced cell adhesion density (P<0.01), increased cell uptake by ~100 folds under hypoxia condition, and destroyed large MCF-7 spheroids by 72 h. Conclusion: Together, APAP@TPZ as biocompatible, and multi-stage activating platforms afford deepened penetration of HAP to hypoxic tumor core, where PEG detachment and TPZ bioreduction into its active form promote selective and effective eradication of hypoxic breast cancer microtumors.

Purpose: Spinal cord ischemia-reperfusion injury (SCII) is initiated following the occlusion of supporting blood vessels, leading to the loss of neurological function. Here, we aimed to study the regenerative properties of tourniquet-induced hindlimb ischemia exosomes (Exos) in SCII Wistar rats.Methods: Exos were isolated from rats following tourniquet-induced hindlimb ischemia. CellTrackerTM CM-DiI-labeled Exos were injected systematically into SCII rats subjected to 60 min of abdominal aorta occlusion. The distribution of Exos was monitored using an immunofluorescence assay. Using histological examination and real-time PCR analysis, glial cell number, pyknotic and swollen neurons, and expression of apoptosis genes were studied. Oxidative stress was examined by measuring the SOD, GPx activity, MDA, and TAC levels. The neurological assessments were also performed 72 hours after the Exo injection. Results: Data revealed cup-shaped spherical Exos with average size and zeta potential of 279.3 nm and 15.6 mV, respectively. The isolated particles were CD9+, CD63+, and CD81+, indicating the existence of typical Exo biomarkers. Histological analysis showed reduced gliosis, pyknotic, and swollen neurons compared to SCII rats after Exos injection (P<0.05). Data indicated the existence of Exos at the site of injury 24 hours after systemic injection. The injection of hypoxic Exos led to inhibition of apoptosis [Bax (~0.6-fold↓), and Bcl-2 (~3.97-fold↑)] and reduction of oxidative stress [MDA (~58%↓), SOD (~310%↑), GPx (~260%↑), and TAC (~300%↑)] compared to SCII rats (P<0.05). Neurological assessments revealed the reduction of withdrawal response and motor deficit index in SCII rats after injection of hypoxic Exos. Conclusion: Hypoxic Exos are valid regenerative tools for the alleviation of spinal cord injury (SCI) following ischemic/reperfusion.