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Gene Jun 2024Fatty acids (FA) are an important factor affecting meat quality and human health, and the important role of the solute carrier family 27 member 6 (SLC27A6) in FA...
Fatty acids (FA) are an important factor affecting meat quality and human health, and the important role of the solute carrier family 27 member 6 (SLC27A6) in FA metabolism has been demonstrated in several species. However, the expression profile of the SLC27A6 in different tissues and the effect of its polymorphism on FA in sheep are currently unknown. This study aimed to explore the differences in FAs in the longissimus dorsi (LD) of 1,085 Hu sheep, the expression profile of SLC27A6, and confirm the effect of single nucleotide polymorphisms (SNPs) on FA phenotypes. We found that many FA phenotypes differ significantly across different seasons, and winter promoted the deposition of polyunsaturated fatty acids (PUFA). The mRNA expression level of SLC27A6 in the lung was significantly higher than that in the heart, testis, and LD. A total of 16 SNPs were detected in the SLC27A6, and 14 SNPs were successfully genotyped by improved multiplex ligase detection reaction (iMLDR) technology. Correlation analysis showed that 7 SNPs significantly affected at least one FA phenotype. Among them, SNP14 contributes to the selection of lamb with low saturated fatty acid content and high PUFA content. Combined genotypes also significantly affected a variety of beneficial FAs such as C18:3n3, C20:4n6, C22:6n3, and monounsaturated fatty acids. This study suggests that SLC27A6 plays an important role in FA metabolism and SNPs that are significantly associated with FA phenotype could be used as potential molecular markers for later targeted regulation of FA profiles in sheep.
PubMed: 38914245
DOI: 10.1016/j.gene.2024.148716 -
Biomarkers in Medicine Jun 2024To evaluate whether can serve as a diagnostic biomarker for glioma. We examined expression in multiple normal and glioma tissues. The diagnostic value of was...
To evaluate whether can serve as a diagnostic biomarker for glioma. We examined expression in multiple normal and glioma tissues. The diagnostic value of was evaluated using receiver operating characteristic curve analysis. The effect of ablation on proliferation, cell cycle and apoptosis was investigated. Database analyses were utilized for functional enrichment analysis. expression in normal tissue was restricted to the human testis. displayed significant diagnostic value in glioma. knockdown inhibited cell proliferation, induced apoptosis and resulted in induction of S-phase cell cycle arrest. Pathway enrichment analysis indicated that may participate in cancer. , a novel cancer/testis gene, may be a potential new diagnostic biomarker for glioma.
PubMed: 38913622
DOI: 10.2217/bmm-2023-0219 -
American Journal of Physiology. Cell... Jun 2024This review provides a rationale for using the Food and Drug Administration (FDA) - approved antibody - drug conjugates (ADCs) for implementing as therapy in recurrent... (Review)
Review
This review provides a rationale for using the Food and Drug Administration (FDA) - approved antibody - drug conjugates (ADCs) for implementing as therapy in recurrent refractory germ cell tumors (rrGCTs) similar to their position in the treatment of other types of chemoresistant solid tumors. GCTs originate from germ cells, they most frequently develop in ovaries or in the testes, whilst being the most common type of malignancy in young men. GCTs are very sensitive to cisplatin - based chemotherapy, but therapeutic resistance occurs in considerable number of cases, which is associated with disease recurrence and poor patient prognosis. ADCs are a novel type of targeted antitumor agents that combine tumor antigen-specific monoclonal antibodies with chemically linked chemotherapeutic drug (payload) exerting a cytotoxic effect. Several FDA - approved ADCs use as targeting moieties the antigens that are also detected in the GCTs, offering a benefit of this type of the targeted therapy even for refractory relapsing TGCT patients unresponsive to standard chemotherapy.
PubMed: 38912730
DOI: 10.1152/ajpcell.00200.2024 -
JCI Insight Jun 2024Spermatogenesis requires precise posttranslational control in the endoplasmic reticulum (ER), but the mechanism remains largely unknown. The protein disulfide isomerase...
Spermatogenesis requires precise posttranslational control in the endoplasmic reticulum (ER), but the mechanism remains largely unknown. The protein disulfide isomerase (PDI) family is a group of thiol oxidoreductases responsible for catalyzing the disulfide bond formation of nascent proteins. In this study, we generated 14 strains of KO mice lacking the PDI family enzymes and found that only PDI deficiency caused spermatogenesis defects. Both inducible whole-body PDI-KO (UBC-Cre/Pdifl/fl) mice and premeiotic PDI-KO (Stra8-Cre/Pdifl/fl) mice experienced a significant decrease in germ cells, testicular atrophy, oligospermia, and complete male infertility. Stra8-Cre/Pdifl/fl spermatocytes had significantly upregulated ER stress-related proteins (GRP78 and XBP1) and apoptosis-related proteins (Cleaved caspase-3 and BAX), together with cell apoptosis. PDI deletion led to delayed DNA double-strand break repair and improper crossover at the pachytene spermatocytes. Quantitative mass spectrometry indicated that PDI deficiency downregulated vital proteins in spermatogenesis such as HSPA4L, SHCBP1L, and DDX4, consistent with the proteins' physical association with PDI in normal testes tissue. Furthermore, PDI served as a thiol oxidase for disulfide bond formation of SHCBP1L. Thus, PDI plays an essential role in protein quality control for spermatogenesis in mice.
Topics: Animals; Male; Spermatogenesis; Protein Disulfide-Isomerases; Mice; Mice, Knockout; Testis; Endoplasmic Reticulum Chaperone BiP; Infertility, Male; Apoptosis; Spermatocytes; Endoplasmic Reticulum Stress; Oligospermia
PubMed: 38912589
DOI: 10.1172/jci.insight.177743 -
Differential gene expression and gut microbiota composition in low-altitude and high-altitude goats.Genomics Jun 2024Previous studies have presented evidence suggesting that altitude exerts detrimental effects on reproductive processes, yet the underlying mechanism remains elusive. Our...
Previous studies have presented evidence suggesting that altitude exerts detrimental effects on reproductive processes, yet the underlying mechanism remains elusive. Our study employed two distinct goat breeds inhabiting low and high altitudes, and conducted a comparative analysis of mRNA profiles in testis tissues and the composition of gut microbiota. The results revealed a reduced testis size in high-altitude goats. RNA-seq analysis identified the presence of 214 differentially expressed genes (DEGs) in the testis. These DEGs resulted in a weakened immunosuppressive effect, ultimately impairing spermatogenesis in high-altitude goats. Additionally, 16S rDNA amplicon sequencing recognized statistically significant variations in the abundance of the genera Treponema, unidentified_Oscillospiraceae, Desulfovibrio, Butyricicoccus, Dorea, Parabacteroides between the two groups. The collective evidence demonstrated the gut and testis played a synergistic role in causing decreased fertility at high altitudes. Our research provides a theoretical basis for future investigations into the reproductive fitness of male goats.
PubMed: 38909906
DOI: 10.1016/j.ygeno.2024.110890 -
International Journal of Surgery Case... Jun 2024Dog bites are a common presentation in emergency departments. However, scrotal injuries with complete testicular avulsion are exceedingly rare.
INTRODUCTION
Dog bites are a common presentation in emergency departments. However, scrotal injuries with complete testicular avulsion are exceedingly rare.
CASE PRESENTATION
We present a case of a dog bite to the scrotum with complete detachment of the testis and right hemiscrotum in an intoxicated 48-year-old man, who was treated with wound irrigation, debridement, antibiotic prophylaxis, tetanus and rabies vaccination, and a covering scrotoplasty.
DISCUSSION
Testicular avulsion following a dog bite to the scrotum is a urologic emergency. Management requires a multidisciplinary approach to address bleeding control, testicular function preservation, infection prevention, and scrotal reconstruction.
CONCLUSION
Dog bites to the scrotum can lead to serious and irreversible complications, underscoring the need for every urologist to be aware and prepared to manage such injuries.
PubMed: 38909389
DOI: 10.1016/j.ijscr.2024.109942 -
BMC Infectious Diseases Jun 2024Nocardia is an ubiquitous soil organism. As an opportunistic pathogen, inhalation and skin inoculation are the most common routes of infection. Lungs and skin are the... (Review)
Review
BACKGROUND
Nocardia is an ubiquitous soil organism. As an opportunistic pathogen, inhalation and skin inoculation are the most common routes of infection. Lungs and skin are the most frequent sites of nocardiosis. Testis is a highly unusual location for nocardiosis.
CASE PRESENTATION
We report the case of an immunocompromised 75-year-old-man admitted for fever of unknown origin. He presented with skin lesions after gardening and was first suspected of Mediterranean spotted fever, but he did not respond to doxycycline. Then, physical examination revealed new left scrotal swelling that was compatible with a diagnosis of epididymo-orchitis. The patient's condition did not improve despite empirical antibiotic treatment with the onset of necrotic scrotal abscesses requiring surgery. Nocardia brasiliensis yielded from the removed testis culture. High-dose trimethoprim-sulfamethoxazole and ceftriaxone were started. Multiple micro-abscesses were found in the brain and spinal cord on imaging studies. After 6 weeks of dual antibiotic therapy for disseminated nocardiosis, slight regression of the brain abscesses was observed. The patient was discharged after a 6-month course of antibiotics and remained relapse-free at that time of writing these lines. Trimethoprim-sulfamethoxazole alone is meant to be pursued for 6 months thereafter. We undertook a literature review on previously reported cases of genitourinary and urological nocardiosis; to date, only 36 cases have been published with predominately involvement of kidney, prostate and testis.
CONCLUSIONS
To the best of our knowledge, this is the first case of Nocardia brasiliensis simultaneously infecting skin, testis, brain and spinal cord in an immunocompromised patient. Knowledge on uncommon forms of nocardiosis remains scarce. This case report highlights the difficulty of diagnosing atypical nocardiosis and the importance of prompt bacteriological sampling in case of empirical antibiotics failure.
Topics: Humans; Male; Nocardia Infections; Aged; Anti-Bacterial Agents; Nocardia; Fever of Unknown Origin; Immunocompromised Host; Trimethoprim, Sulfamethoxazole Drug Combination; Testis; Orchitis
PubMed: 38907186
DOI: 10.1186/s12879-024-09521-8 -
Chemico-biological Interactions Jun 2024Breast cancer resistance protein/ATP-binding cassette subfamily G2 (BCRP/ABCG2) is an ATP-binding cassette efflux (ABC) transporter expressed in the apical membrane of...
Breast cancer resistance protein/ATP-binding cassette subfamily G2 (BCRP/ABCG2) is an ATP-binding cassette efflux (ABC) transporter expressed in the apical membrane of cells in tissues, such as the liver, intestine, kidney, testis, brain, and mammary gland. It is involved in xenobiotic pharmacokinetics, potentially affecting the efficacy and toxicity of many drugs. In this study, the role of ABCG2 in parasiticide monepantel (MNP) and its primary metabolite, monepantel sulfone (MNPSO)'s systemic distribution and excretion in milk, was tested using female and male wild-type and Abcg2 mice. Liquid chromatography coupled with a tandem mass spectrometer (LC-MS/MS) was used for the analysis in a 10-min run time using positive-mode atmospheric pressure electrospray ionization (ESI+) and multiple reaction monitoring (MRM) scanning. For the primary metabolite tested, milk concentrations were 1.8-fold higher in wild-type mice than Abcg2 female lactating mice (P = 0.042) after intravenous administration of MNP. Finally, despite the lack of a difference between groups, we investigated potential differences in MNP and MNPSO's plasma and tissue accumulation levels between wild-type and Abcg2 male mice. In this study, we demonstrated that MNPSO milk levels were affected by Abcg2, with potential pharmacological and toxicological consequences, contributing to the undesirable xenobiotic residues in milk.
PubMed: 38906501
DOI: 10.1016/j.cbi.2024.111117 -
Urology Jun 2024To characterize changes in body composition following cytotoxic chemotherapy for germ cell carcinoma of the testis (GCT) and quantify associations between body...
A Multicenter Evaluation of Treatment-Associated Changes in Body Composition in Men with Germ Cell Tumors (GCT) of the Testis: Implications for Adverse Events and Complications.
OBJECTIVES
To characterize changes in body composition following cytotoxic chemotherapy for germ cell carcinoma of the testis (GCT) and quantify associations between body composition metrics and chemotherapy-associated adverse events (AEs) and post-retroperitoneal lymph node dissection (RPLND) complications.
MATERIALS AND METHODS
This retrospective multi-center study included 216 men with GCT treated with cytotoxic chemotherapy and/or RPLND (2005-2020). We measured body composition including skeletal muscle (SMI), visceral adipose (VAI,), subcutaneous adipose (SAI), and fat mass (FMI) indices on computed tomography. We quantified chemotherapy-associated changes in body composition and evaluated associations between body composition and incidence of grade 3+ AEs and post-RPLND complications on multivariable logistic regression analyses.
RESULTS
182 men received a median of 3 cycles of cisplatin-based chemotherapy. Following chemotherapy, median change in SMI was -6% (p=<0.0001), while VAI, SAI, and FMI increased by +13% (p=<0.0001), +11% (p=<0.0001), and +6% (p=<0.0001), respectively. 79 patients (43%) experienced at least one grade 3+ AE. A decrease in SMI following chemotherapy was associated with increased risk of grade 3+ AEs (p=0.047). 103 men with a median age of 28.5 years (IQR 23-35.5) underwent RPLND of whom 22 (21.3%) experienced at least one grade 3+ post-RPLND complication. No baseline body composition metrics were associated with post-RPLND complications.
CONCLUSIONS
In men with GCT of the testis, chemotherapy was associated with 6% loss of lean muscle mass and gains in adiposity. Lower skeletal muscle was associated with a higher incidence of chemotherapy-associated AEs. Body composition was not associated with the incidence of post-RPLND complications.
PubMed: 38906271
DOI: 10.1016/j.urology.2024.06.030 -
International Journal of Biological... 2024Epizootic hemorrhagic disease (EHD), caused by Epizootic hemorrhagic disease virus (EHDV), is an emerging and severe livestock disease. Recent incursion and distribution...
Epizootic hemorrhagic disease (EHD), caused by Epizootic hemorrhagic disease virus (EHDV), is an emerging and severe livestock disease. Recent incursion and distribution of EHDV in Europe have outlined the emerging character of EHD. Despite its worldwide impact, numerous knowledge gaps exist. A range of inconveniences restricts utilization of natural hosts of EHDV. Here, we show that adult mice deficient in type I IFN receptor (IFNAR(-/-)) are highly susceptible to EHDV-6 and EHDV-8 infection when the virus is administered subcutaneously. Disease was characterized by ruffled hair, reluctance to move, dehydration and conjunctivitis, with viraemia detected from day 5 post-infection. A deeper characterization of EHDV-8 infection showed viral replication in the lung, liver, spleen, kidney, testis and ovaries. Importantly, increased expression levels of pro-inflammatory cytokines IL-1β, IL-6 and CXCL2 were observed in spleen after EHDV-8 infection. Furthermore, IFNAR(-/-) adult mice immunized with a EHDV-8 inactivated vaccine elicited neutralizing antibodies specific of EHDV-8 and full protection against challenge with a lethal dose of this virus. This study also explores the possibilities of this animal model for study of BTV and EHDV coinfection. In summary, the IFNAR(-/-) mouse model faithfully recapitulates EHD and can be applied for vaccine testing, which can facilitate progress in addressing the animal health challenge posed by this virus.
Topics: Animals; Mice; Receptor, Interferon alpha-beta; Disease Models, Animal; Hemorrhagic Disease Virus, Epizootic; Viral Vaccines; Reoviridae Infections; Female; Mice, Knockout; Antibodies, Neutralizing; Male
PubMed: 38904031
DOI: 10.7150/ijbs.95275