Male infertility is a multifactorial condition, with an increasing body of evidence highlighting the pivotal role of seminal plasma biochemical markers and microbial infections in its pathogenesis and diagnosis. Seminal plasma, a complex fluid enriched with proteins, enzymes, antioxidants, and metabolites, reflects the functional status of the male reproductive tract. Alterations in its biochemical composition such as decreased antioxidant capacity, disrupted energy metabolism, and elevated inflammatory mediators, are frequently associated with impaired sperm function. Concurrently, microbial infections, including those caused by Chlamydia trachomatis and Escherichia coli, can adversely affect seminal parameters through direct sperm damage, oxidative stress, and inflammatory responses. Emerging evidence suggests intricate interactions between infections and biochemical milieu in seminal plasma, which may exacerbate sperm dysfunction and compromise fertility. This review synthesizes current knowledge on key seminal plasma biomarkers and their diagnostic utility, and elucidates the pathophysiological mechanisms linking microbial infections to male infertility. Understanding these interconnected pathways offers novel insights into male reproductive health and may facilitate the development of more targeted diagnostic and treatment strategies in the context of infertility.

Hyaluronidase, a group of enzymes that catalyze the hydrolysis of hyaluronic acid, plays a pivotal role in modulating the extracellular matrix and enhancing tissue permeability. Hyaluronidase has gained widespread attention for its diverse biochemical properties and expanding therapeutic potential. This review provides a comprehensive overview of hyaluronidase, focusing on its biochemical characteristics, mechanisms of action, and regulatory pathways. We examine its utility in preclinical models, highlighting its role in drug delivery, tissue remodeling, and cancer research. Clinically, hyaluronidase has been employed in various domains including ophthalmology, dermatology, oncology, and as an adjuvant in subcutaneous and intramuscular drug administration. Additionally, its role in reversing complications of dermal filler injections has led to increased use in aesthetic medicine. Despite its broad application, challenges such as immunogenicity, variability in enzyme sources, and potential adverse effects warrant continued investigation. Through an integrated analysis of current evidence, this review aims to elucidate the multifaceted roles of hyaluronidase and explore its emerging applications in modern medicine.

Objectives: Type 2 diabetes (T2D) is a prevalent metabolic disorder characterized by insulin resistance and impaired glucose metabolism, often leading to severe complications. Emerging evidence suggests that exercise, particularly resistance training and aerobic activities, can significantly improve glycemic control and overall health in individuals with T2D. This study aimed to assess resistance and aerobic training, both with and without Blood Flow Restriction (BFR) and genetic polymorphisms located in the miR143/145 and IGF2BP2 gene clusters in men with T2D.

Methods:  A total of 30 men with T2D were randomly assigned to four groups: resistance training with BFR (RT-BFR), resistance training without BFR (RT), aerobic training with BFR (AT-BFR), and aerobic training without BFR (AT) and two control groups. Training sessions were conducted three times per week for 12 weeks, followed by a 6-week detraining period. Genotyping was performed for polymorphisms within the miR143/145 and IGF2BP2 gene clusters by ARMS-PCR.

Results: The results of our study showed that in the AT group, the dominant genotype was TT_rs4705342TT_rs4705343GG_rs4402960AA_rs1470579. In the RT group and the Control AT group, the dominant genotype was TT_rs4705342TT_rs4705343GG_rs4402960CC_rs1470579. And also, in other groups (including AT-BFR and RT-BFR group and Control RT group) the dominant genotype was TT_rs4705342TT_rs4705343GG_rs4402960AC_rs1470579. The results were AT vs. Control AT at the rs4402960 position in the recessive model. Therefore, the risk decreased by 0.74 for TT vs. GT+GG (p-value = 0.025). Moreover, the RT group vs. Control RT group at the rs1470579 position in the same model, yielded significant results, leading to a 14-fold increase in risk for CC vs. AC+AA (p-value < 0.001).

Conclusion:The findings from this research contribute valuable evidence to the ongoing discourse surrounding exercise, genetics, and diabetes management.

Objectives:  This study investigated the effects of aqueous chicory seed extract (CSE), metformin (Met), and aspirin (Asp) on the Renin-Angiotensin System (RAS) in healthy Wistar rats, as well as in early (NIA/STZ) and late-stage diabetes (STZ).

Methods: Rats were divided into Control, NIA/STZ, and STZ groups. NIA/STZ rats received niacinamide/streptozotocin, while STZ rats received STZ to induce early and late diabetes stages. Subgroups received CSE (125 mg/kg), metformin (100 mg/kg), or aspirin (120 mg/kg). Measurements included mRNA levels of AGT, ACE, ACE2, activities of ACE and ACE2, levels of Ang II and Ang-(1-7), protein carbonyl content (PCC), nitric oxide (NO), and kidney collagen.

Results: Late-stage diabetes (STZ) decreased AGT, ACE, and ACE2 mRNA, but increased ACE activity, Ang II, Ang-(1-7), the ACE/ACE2 ratio, PCC, and collagen. CSE increased AGT and ACE2 mRNA, decreased ACE activity, Ang II, the ACE/ACE2 ratio, and PCC. Metformin boosted AGT mRNA and reduced PCC and collagen. Aspirin lowered collagen. Early diabetes (NIA/STZ) decreased AGT, ACE2, and Ang-(1-7), while increasing ACE activity and Ang II levels. CSE increased AGT and Ang-(1-7), reducing Ang II and the Ang II/Ang-(1-7) ratio. Metformin reduced ACE mRNA and increased Ang-(1-7). CSE decreased reactive oxygen species (ROS) and improved Ang-(1-7) levels, especially in early stages. Both CSE and metformin helped reduce fibrosis.

Conclusion:     Our findings suggest that CSE supports renal tissue repair in both early and late stages of T2D by increasing the levels of the protective peptide Ang-(1-7), respectively.

Objectives: Triple-negative breast cancer (TNBC) is a hyperaggressive kind of breast cancer, due to its lack of therapeutic options, as it lacks hormonal receptors. Today, the only potential drug in the treatment of this subtype is chemotherapy, however drug resistance occurs after a while. In this study, we aimed to develop a co-culture organoid model to analyze the contribution of ''fibroblast'' on TNBC cell invasion and chemoresistance.

Methods: A two-cell organoid model using the MDA-MB-231 cell line, a model cell for TNBC, and primary human foreskin fibroblasts (HDFs), was established. Their invasion and chemotherapy response were evaluated.

Results: Our data shows that the fibroblasts made the invasion and chemoresistance easier. Hence, the important role of fibroblasts in modulating TNBC cell behavior was substantiated because the contribution of fibroblasts in TME was shown to promote invasion phenotype enhancement and decrease sensitivity to chemotherapy drugs.

Conclusion: This study points out the significance of an organoid model in reproducing the tumor environment (TME), hence, it brings evidence for the involvement of fibroblasts in the formation of TNBC. Thereby, the increased drug resistance and invasion observed in organoids with fibroblasts further advocate the relevance of targeting the TME components when conceiving future therapeutic strategies for TNBC.

Objectives: Transient Neonatal Tyrosinemia (TNT) is a benign, self-limiting disorder characterized by elevated blood tyrosine levels in neonates. It is often caused by immature hepatic enzymes, particularly 4-hydroxyphenylpyruvate dioxygenase (4-HPPD), and may be influenced by factors such as prematurity, low birth weight, and high protein intake. Early detection via newborn screening is essential to differentiate TNT from more serious disorders like tyrosinemia type I. The aim of this study if to determine the incidence of TNT and identify perinatal factors associated with its development in Iranian neonates.

Methods: This retrospective case-control study reviewed newborn screenings performed at the Growth and Development Research Center's metabolic laboratory between March 2019 and February 2023. The control group comprised newborns with normal metabolic screening results during the study period.

Results: Metabolic screenings were conducted on 73,349 infants. The incidence of TNT was found to be 0.47%, corresponding to a total of 345 diagnosed cases. TNT infants had a lower gestational age (37.7±1.4 weeks), lower birth weight (3.35±1.6 kg), and a higher rate of cesarean deliveries (83.9%) compared to the control group (P<0.05). Logistic regression analysis showed significant associations between TNT and preterm birth (OR: 868.2, 95% CI: 168.9–4212.7, P<0.00), cesarean delivery (OR: 3.5, 95% CI: 2.26–5.3, P<0.00), and gestational age (OR: 0.17, 95% CI: 0.12–0.24, P<0.00). No significant association was found with the other parameters (P≥0.05).

Conclusion: TNT incidence in Iranian newborns is associated with prematurity and cesarean delivery. Optimizing screening protocols and encouraging vaginal delivery when possible, may reduce TNT rates.

Objectives: Acetaminophen overdose may lead to acute pulmonary complications like acute lung injury because of its overdose harmful effect on cellular systems due to oxidative stress. leucomethylene blue (LMB) may have beneficial effects by improving hemodynamic stability and reducing oxidative damage through its nitric oxide synthase inhibitory and antioxidant activities. This study aimed to evaluate the effect of LMB on acetaminophen-induced pulmonary injury in rats.

Methods: Lung samples were collected from 30 male Wistar rats, which were randomly split into five groups, and frozen for later analysis. The groups included control, acetaminophen, N-acetylcysteine (NAC) treated, LMB treated, and NAC+LMB combination treated. We evaluated total antioxidant capacity (TAC), glutathione reductase (GR), TNF-α and IL-6 levels, histopathology, and relevant tissue remodeling changes.

Results: Our results demonstrated that the administration of LMB greatly diminished the oxidative and inflammatory damage caused by APAP toxicity in the lungs. LMB restored TAC and GR activity that were significantly depressed by APAP toxicity. Additionally, LMB restricted the overproduction of pro-inflammatory cytokines that were released from lung tissue. Moreover, LMB substantially counteracted the pulmonary lesions caused by APAP, including edema, hemorrhage, and inflamed cells, corroborated by histopathological analysis.

Conclusion: The results of this study showed that LMB can effectively reduce lung damage caused by acetaminophen poisoning.