Varicocele, a common condition affecting male fertility, has been linked to impaired semen quality and elevated sperm DNA fragmentation (SDF). This study aimed to evaluate the epidemiological prevalence of varicocele and SDF in infertile men and compare the effectiveness of microsurgical varicocelectomy and antioxidant therapy in improving semen parameters and reducing SDF.
This multi-center study included 3632 subfertile and 276 fertile men in the epidemiological phase (retrospective) and 182 infertile men in the comparative analysis phase (prospective). Patients were stratified into three groups: Group 1 (microsurgical varicocelectomy, n = 86), Group 2 (antioxidant therapy, n = 63), and Group 3 (control, n = 33). Varicocele prevalence, semen parameters, and SDF levels were assessed, with follow-up evaluations conducted three months post-intervention. Semen parameters were evaluated using the World Health Organization (WHO) Fifth Edition guidelines, and SDF was measured using the sperm chromatin dispersion test.
Varicocele was observed in 29.5% of subfertile men and 27.2% of fertile men, with no statistically significant difference noted (p = 0.18). However, subfertile men with varicocele exhibited significantly higher median SDF levels (20.8%, interquartile range (IQR): 14.1–27.9) compared to fertile men (12.3%, IQR: 9.1–16.5; p < 0.001). Microsurgical varicocelectomy significantly improved semen parameters, with the median sperm concentration increasing by +25.0 million/mL (IQR: 18.4–31.5; p < 0.001) and progressive motility by +67.0% (IQR: 50.0–83.5; p < 0.001). Antioxidant therapy yielded moderate improvements in sperm concentration (+11.0 million/mL, IQR: 8.0–14.5; p < 0.001) and motility (+6.0%, IQR: 4.0–8.5; p = 0.01). The control group showed no significant changes.
This study reveals comparable varicocele prevalence between subfertile (29.5%) and fertile men (27.2%), with impaired semen quality and elevated SDF levels in subfertile cases. Microsurgical varicocelectomy proved most effective, while antioxidant therapy offered a viable alternative or adjunct for non-surgical candidates, underscoring the need for tailored varicocele infertility treatments.
The enterotype concept allows the differentiation of gut microbiota in relation to individual characteristics and is determined by the genetics and external stressors of the host. It was previously shown that not all clustering methods can accurately identify such enterotypes. Therefore, this pilot study primarily aimed to compare different algorithms for enterotype definition and to estimate the factors that correlate with the differentiation of the gut microbiota in adolescents with different body weights.
Adolescents with normal body weight (N) and obesity (O) (aged 11–17 years) were included in this pilot study. Based on the analysis of the V3–V4 variable regions of the 16S ribosomal RNA gene amplicon libraries, the main enterotypes of the gut microbiota of adolescents were characterized using three approaches (E-typing A, B, and C) according to the bacterial taxa that were chosen for differentiation. For sample clustering, we used Bray–Curtis, Jensen–Shannon divergence, and weighted and unweighted UniFrac distance metrics. Clustering was assessed using the silhouette index. Meanwhile, the Kruskal–Wallis test was used to determine the relationship between enterotype and biochemical parameters.
The O and N groups comprised 18 and 22 adolescents, respectively, and, according to anthropometric data, differed significantly only in weight and body mass index (BMI). The linear discriminant analysis effect size (LEfSe) plot showed that the presence of minor and rare phylotypes in the gut microbiota differed between the two groups of adolescents. The distribution of individual samples based on the principal coordinates analysis (PCoA) showed that the gut microbiomes in the adolescents were not grouped in the N or O groups but were distributed according to the composition of the main bacterial taxa. We assessed the contribution of the Bacteroides, Prevotella, Subdoligranulum, and Ruminococcus phylotypes to the microbiota of the adolescents in the two groups. The Subdoligranulum enterotype was significantly more represented in the N group than in the O group when the E-typing A approach to enterotyping was applied. Pairwise comparisons were performed with corrections for multiple testing between the biochemical parameter levels of the different enterotypes. Bilirubin levels were lower in adolescents with the gut microbiota enterotype Ruminococcus–Subdoligranulum than in those with the enterotype Bacteroides when the E-typing B approach was used for differentiation.
This pilot study comprised a small group of adolescents with normal body weight and obesity; we identified Bacteroides as the main enterotype, regardless of body weight. A stable microbial community is formed in the gut during adolescence, which determines its stratification by enterotype.
Kidney disease is a growing public health problem globally. Multiple or repeated acute injuries to the kidney due to chronic exposure to toxicants promote the development of chronic kidney disease (CKD), an irreversible disease for which there is no current treatment. Renal fibrosis, characterized by glomerulosclerosis and tubulointerstitial fibrosis, is a well-known pathological stage during the progression of acute kidney injury (AKI) to CKD. Over the years, tremendous progress has been made in understanding the regulatory molecules involved in kidney fibrosis; however, there are currently no effective therapies for treating renal fibrosis. The mechanism involved in the transition of AKI to fibrosis and its progression to CKD involves various pathological changes, including cellular remodeling. At the molecular level, these pathological features are mediated by changes in the expression of genes and signaling pathways that control cellular dedifferentiation. Meanwhile, the generation of oxidative stress is a common feature of nephrotoxicants. Thus, the kidneys are highly susceptible to oxidative stress-induced injury, and accumulating evidence suggests that oxidative stress plays a causative role in the development of kidney disease. Oxidative stress has been shown to modulate various signaling pathways associated with AKI and fibrogenic changes in the kidney. Accumulating evidence suggests that targeting oxidative stress through antioxidants and/or inhibitors of reactive oxygen species (ROS)-regulated pathways holds promise for the clinical management of this disease, for which there is currently no effective therapy. This review summarizes the research development that provides a mechanistic perspective on the role of oxidative stress in regulating of target genes and signaling pathways associated with AKI and CKD. Additionally, recent reports highlighting the clinical significance of targeting oxidative stress for the treatment of CKD are discussed.
Leaf rust caused by Puccinia triticina Erikss. is a widely distributed wheat (Triticum aestivum L.) disease. Using wild relatives, such as Triticum spelta L., as a source of desirable traits represents a good strategy for developing wheat varieties, as T. spelta L. has shown tolerance to various types of biotic and abiotic stresses. This study aimed to determine the genetic basis of resistance to leaf rust in the accession Triticum spelta 109 (PI 355580).
The resistant genotype T. spelta 109 was crossed with the bread wheat variety Roelfs F2007, and 135 F3 families were generated to analyze the genetics of resistance to the MBJ/SP leaf rust race. The families were classified into three groups: (i) homozygous-resistant; (ii) homozygous-susceptible; (iii) segregating. A χ2 test was performed to compare whether the expected and observed segregation ratios fit and to determine the number of genes involved in the resistance of T. spelta 109.
The seedling tests in the F1 generation showed susceptibility in all plants, indicating that the resistance is conferred by a recessive gene(s). The results of the χ2 test revealed that the observed segregation ratios of the F3 families followed the expected values, suggesting that a recessive gene confers the leaf rust resistance present in T. spelta 109. According to our results and the reported recessive genes identified among the T. spelta accessions, the identified recessive gene in T. spelta 109 (PI355580) is different and most likely a novel leaf rust resistance gene.
The genetic resistance to leaf rust of T. spelta 109 (PI 355580) is conferred by a single recessive gene. The importance and usefulness of searching for rust resistance genes from different sources and incorporating them into the genetic base of wheat breeding programs to provide diversity is confirmed.
Hydatidosis, caused by Echinococcus granulosus, is a neglected zoonotic disease with significant public health implications in endemic regions, such as in Cusco, Peru. Genetic factors influencing susceptibility to infection and responses to albendazole, the primary treatment, remain unclear. Thus, this study aimed to investigates genetic polymorphisms associated with hydatidosis susceptibility and albendazole metabolism in the Cusco region.
Hence, a cross-sectional study was conducted using 20 individuals from endemic areas. Peripheral blood samples were collected for genomic DNA extraction, followed by single-nucleotide polymorphism (SNP) genotyping using the Illumina Global Screening Array. Polymorphisms in genes related to immunity (interleukin 10 (IL10), interleukin 17A (IL17A), vitamin D receptor (VDR), interferon gamma (IFNG), forkhead box P3 (FOXP3), interleukin 4 (IL4), tumor necrosis factor (TNF), toll-like receptor 4 (TLR4), cytotoxic T-lymphocyte antigen 4 (CTLA4), mannose-binding lectin 2 (MBL2), interleukin 12B (IL12B), and transforming growth factor-beta 1 (TGFB1)) and drug metabolism genes (cytochrome P450 family 3 subfamily A member 4 (CYP3A4), cytochrome P450 family 2 subfamily B member 6 (CYP2B6), cytochrome P450 family 1 subfamily A member 2 (CYP1A2), ATP-binding cassette subfamily B member 1 (ABCB1), solute carrier organic anion transporter family member 1B1 (SLCO1B1), and cytochrome P450 family 2 subfamily E member 1 (CYP2E1)) were analyzed.
High-frequency alleles were identified in six SNPs associated with susceptibility to Echinococcus granulosus: IL10 rs1800896 (77.5%), IL17A rs2275913 (97.5%), IFNG rs2779249 (92.5%), FOXP3 rs11568821 (97.5%), TGFB1 rs1800469 (80.0%), and VDR rs2228570 (87.5%). Likewise, elevated allele frequencies were observed for two SNPs potentially involved in albendazole metabolism: CYP3A4 rs2740574 (87.5%) and CYP2B6 rs2266780 (97.5%). A comparative analysis with other populations revealed significant differences in SNP frequencies in the Cusco population, both in SNPs related to susceptibility (IL17A rs2275913, VDR rs2228570, and TGFB1 rs1800469; p < 0.001) and pharmacogenetic-related SNPs (CYP2B6 rs2266782, SLCO1B1 rs4149056, and CYP2E1 rs8330; p < 0.05), suggesting the existence of unique local genetic patterns.
These findings underscore the importance of pharmacogenetic screening to optimize albendazole therapy and support precision medical approaches for hydatidosis management in endemic regions. Further studies with larger cohorts are required to confirm these associations.