Reproductive Issues Research Articles

CD56-Positive NK Cells and CD138-Positive Plasma Cells in Basal Decidua of Term Placentas in Singleton Pregnancies After Assisted Reproductive Technology Treatment of Endometriosis-Related Infertility

A eutopic endometrium in endometriosis shows altered immune responses, including abnormalities of NK cells and expression of plasma cells, related to reproductive issues. This study investigated the counts of CD56-positive NK cells and CD138-positive plasma cells in the basal decidua of term placentas in singleton pregnancies after endometriosis-related infertility conceived by assisted reproductive technology (ART). This single-center, case-control study involved immunohistochemical analysis of CD56-positive NK cells and CD138-positive plasma cells in basal decidua using primary monoclonal mouse antibodies, followed by secondary antibodies using a standardized protocol. CD56 and CD138 immunohistochemically positive cells were reported as the total cell count for each studied antibody expressed per 1 mm2 of basal decidua (Olympus BX46 and Olympus Image Analyzer). Placental samples containing basal decidua from 36 participants with endometriosis-related infertility who conceived by ART, 31 participants with male factor infertility who conceived by ART and 40 healthy controls were included. Endometriosis decidua showed the lowest median count of CD56-positive NK cells (11.5 / mm2, p = 0.039) in BD compared to male factor group (25 / mm2) and healthy controls (24.5 / mm2). No differences were found for CD138-positive plasma cells counts between study groups. Basal decidua in pregnancies after endometriosis-related infertility showed reduced total count of CD56-positive NK cells, without differences in the CD138-positive plasma cell counts compared to control groups. Future studies should investigate how changes in NK cells throughout pregnancy affect the development of perinatal complications and placental pathologies in women with endometriosis, which could uncover potential diagnostic and therapeutic targets.

Effects of coenzyme q10 supplementation on metabolic and reproductive outcomes in obese rats

Obesity, a global epidemic, is linked to adverse reproductive outcomes, including infertility and ovulation dysfunction. The cafeteria diet (CAF) serves as an animal model mirroring Western diet habit. Coenzyme Q10 (CoQ10), known for enhancing reproductive outcomes in various pathologies, is not fully understood for its effects on obesity treatment. Here, obesity was modeled using CAF-fed rats to assess CoQ10's impact on metabolic and ovarian disruptions caused by obesity. Wistar rats were divided into control (standard diet) and obese (CAF diet) groups. After 75 days, half of each group received oral CoQ10 (5 mg/kg) for 13 days, while the rest received a vehicle. Animals were euthanized during the estrus phase, and blood and ovaries were collected for analysis. CAF caused increased body weight gain (p < 0.01) associated with hyperglycemia, hypertriglyceridemia, and hypercholesterolemia (p < 0.05). Moreover, it caused a reduction in the number of AMH + follicles (p < 0.001), increasing follicular atresia (p < 0.05) and serum estradiol levels (p < 0.05). Obesity also altered the estrous cycle and reduced the ovulation rate (p < 0.05). CoQ10 administration showed beneficial effects on all ovarian disruptions but had no effect on the metabolic alterations induced by obesity. In summary, CoQ10 could be an additional treatment for obesity-related infertility in patients with normal metabolic profiles. While CoQ10 does not affect metabolic parameters influenced by obesity, crucial for reproductive issues and offspring health, it is recommended as part of a treatment plan that includes a balanced diet and increased physical activity for obese individuals with metabolic alterations seeking pregnancy.

KDIGO 2025 clinical practice guideline for the evaluation, management, and treatment of autosomal dominant polycystic kidney disease (ADPKD): executive summary.

The Kidney Disease: Improving Global Outcomes (KDIGO) 2025 Clinical Practice Guideline for the Evaluation, Management, and Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) represents the first KDIGO guideline on this subject. Its scope includes nomenclature, diagnosis, prognosis, and prevalence; kidney manifestations; chronic kidney disease (CKD) management and progression, kidney failure, and kidney replacement therapy; therapies to delay progression of kidney disease; polycystic liver disease; intracranial aneurysms and other extrarenal manifestations; lifestyle and psychosocial aspects; pregnancy and reproductive issues; pediatric issues; and approaches to the management of people with ADPKD. The guideline has been developed with patient partners, clinicians, and researchers around the world, with the goal to generate a useful resource for healthcare providers and patients by providing actionable recommendations. The development of this guideline followed an explicit process of evidence review and appraisal, based on a rigorous, formal systematic literature review. The strength of recommendations follows the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The guideline also provides practice points serving to direct clinical care or activities relating to areas for which a systematic review was not conducted. Limitations of the evidence are discussed. Research recommendations to address gaps in knowledge, and implications for policy and payment, are provided. The guideline targets a broad audience of healthcare providers, people living with ADPKD, and stakeholders involved in the various aspects of ADPKD care.

Spinal Muscular Atrophy Update in Best Practices: Recommendations for Treatment Considerations.

Spinal muscular atrophy (SMA) is an autosomal recessive disorder caused by biallelic variants of the Survival Motor Neuron 1 gene (SMN1) that affects approximately 1 in 15,000 live births. Availability of 3 SMN-enhancing treatments for SMA has led to urgency to review how clinicians and patients use these treatments for SMA, while additional research and real-world data and experience are being collected. This work describes important factors to assist with decision-making for SMN-enhancing treatments. A systematic literature review was conducted on SMN-enhancing treatments for SMA and related studies. A working group of American and European health care providers with expertise in SMA care identified barriers and developed recommendations through a modified Delphi technique with serial surveys and feedback through virtual meetings to fill gaps for information where evidence is limited. A community working group of an individual living with SMA and caregivers provided insight and perspective on SMA treatments and support through a virtual meeting to guide recommendations. The health care provider working group and the community working group agreed that when determining whether to start, change, add, or discontinue a treatment, essential considerations include patient and family/caregiver perspective, and treatment safety and side effects. When initiating treatment for patients newly diagnosed with SMA, important patient characteristics are age and Survival Motor Neuron 2 gene (SMN2) copy number. Furthermore, when initiating, changing, or adding treatment, current clinical status and comorbidities drive decision-making. When considering a medication or treatment plan change, unless there is an urgent indication, a treatment and associated patient outcomes should be monitored for a minimum of 6-12 months. When determining a treatment plan with an adolescent or adult with SMA, consider factors such as quality of life, burden vs benefit of treatment, and reproductive issues. Access to care coordination and interdisciplinary/multidisciplinary care are essential to treatment success. Sharing information about current knowledge of treatments and shared decision-making between health care providers and patients living with SMA and caregivers are essential to overcoming barriers to providing SMN-enhancing treatments.

The issues of personnel reproduction in the transport and logistics industry: Formulation and solution in the context of relevant cases of the global market of online industry education

The issues of personnel reproduction in the transport and logistics industry: Formulation and solution in the context of relevant cases of the global market of online industry education

New Directions For Women's Health: Expanding Understanding, Improving Research, Addressing Workforce Limitations.

In the United States, the field of women's health faces critical challenges. This article, part of the National Academy of Medicine's Vital Directions for Health and Health Care: Priorities for 2025 initiative, emphasizes the need for a holistic, lifespan approach to women's health that considers biological sex, gender, and intersecting social factors. We identify three key challenges: broadening the understanding of women's health beyond reproductive issues, improving the research ecosystem, and addressing workforce limitations. With innovative policies and investments across all areas of health, attention to structural determinants, and emphasis on the upstream factors affecting women's lives, significant improvements in women's health outcomes and substantial societal benefits can be achieved in 2025 and beyond.

Intradermal lymphocyte therapy: A promising treatment for recurrent pregnancy loss in patients without anti-TPO antibodies.

Recurrent pregnancy loss (RPL) remains a complex and challenging reproductive issue often associated with immunological abnormalities. This study investigates the immunomodulatory effects of intradermal lymphocyte therapy in RPL patients, exploring cellular, molecular, and cytokine changes, with specific attention to individuals with positive anti-thyroid peroxidase antibodies (Anti-TPO). The study included 105 patients with RPL, divided into Anti-TPO positive RPL patients (n=25), Anti-TPO negative RPL patients (n=38), and RPL patients without lymphocyte immunotherapy (LIT) (n=42). LIT was administered according to a standardized protocol, and various immune parameters including flow cytometry analysis of Th1/Th2, Th17, Treg, and NK cells, real-time PCR analysis of gene expression levels, and ELISA analysis of cytokine levels were assessed before and after LIT. Clinical outcomes including clinical miscarriage rates, delivery or pregnancy rates, and live birth rates were also evaluated. Flow cytometry analysis revealed significant decreases in Th1/Th2 and NK cell percentages post-LIT in both Anti-TPO positive and negative RPL patients. Real-time PCR analysis showed significant alterations in gene expression levels of FoxP3, T-bet, GATA3, RORγt, IL-17, TGF-β, IFNγ, and IL-4 post-LIT in both groups. ELISA analysis demonstrated significant changes in levels of IL-17, TGF-β, IFNγ, and IL-4 post-LIT in both groups. Anti-TPO negative RPL patients with LIT had a lower miscarriage rate (10.53%) compared to Anti-TPO positive RPL patients with LIT (40%). Also, the pregnancy rate and the live birth rate were higher (89.47%) in Anti-TPO negative RPL patients with LIT compared to Anti-TPO positive RPL patients with LIT (60% and 56% respectively). Moreover, the average pregnancy rate and live birth rate were significantly higher in RPL patients with LIT than in those without LIT (30.95%). These findings suggest that while LIT may confer benefits in improving pregnancy outcomes, its efficacy may be influenced by the presence of Anti-TPO Abs. These findings highlight the complex interplay between immune dysregulation and pregnancy outcomes in RPL patients and underscore the need for personalized treatment approaches.

Insights into Solea senegalensis Reproduction Through Gonadal Tissue Methylation Analysis and Transcriptomic Integration.

Fish exhibit diverse mechanisms of sex differentiation and determination, shaped by both external and internal influences, often regulated by distinct DNA methylation patterns responding to environmental changes. In S. senegalensis aquaculture, reproductive issues in captivity pose significant challenges, particularly the lack of fertilization capabilities in captive-bred males, hindering genetic improvement measures. This study analyzed the methylation patterns and transcriptomic profiles in gonadal tissue DNA from groups differing in rearing conditions and sexual maturity stages. RRBS (Reduced Representation Bisulfite Sequencing) was employed to detect notable methylation variations across groups, while RNA was extracted and sequenced for differential expression analysis. Our findings suggest that DNA methylation significantly regulates gene expression, acting as a mechanism that can both repress and enhance gene expression depending on the genomic context. The complexity of this epigenetic mechanism is evident from the varying levels of methylation and correlation rates observed in different CpGs neighboring specific genes linked to reproduction. Differential methylation comparisons revealed the highest number of differently methylated CpGs between maturation stages, followed by rearing conditions, and lastly between sexes. These findings underscore the crucial role of methylation in regulating gene expression and its potential role in sex differentiation, highlighting the complex interplay between epigenetic modifications and gene expression.

Medicinal plant species used for contraception and reproductive health care in rural Uganda.

Medicinal plants form an integral part of traditional health care systems in Uganda and are known to possess a variety of bioactive compounds some of which are beneficial as contraceptives. This study documented indigenous traditional knowledge on medicinal plant species used in contraception and other reproductive health care-related issues in rural Uganda. An ethnobotanical study was conducted from December 2019 to August 2020 in four different regions of Uganda: Mpigi, Kamuli, Bushenyi and Arua. Data was obtained from 158 traditional medical practitioners using semi-structured questionnaires. Descriptive statistics were used to present the data while quantitative analysis of data was done using the informant consensus factor (FIC), Percentage Use Value (PUV) and Jaccard Index (JI). The study recorded 98 medicinal plant species with the potential to manage family planning and other reproductive health related conditions. The most represented family was Asteraceae with 18 species. Plant remedies were mainly prepared as decoctions (41%) and administered orally (36%). Most plant species (61%) were harvested from wild habitats. Herbs (50%) and leaves (50%) contributed the highest percentage of plant growth forms and parts used respectively. The FIC value of 0.6 demonstrated that the herbalists, traditional birth attendants and community elders tend to agree with each other regarding plant species used and administration. JI ranged from 13 % to 0.9 %, an indication of very low similarities between the plants used in family planning and traditional health care among the communities in the study areas. The most frequently cited plant species for family planning management were: Prunus africana (Hook.f.) Kalkman (14: with a PUV of 45.2 %): Sporobolus pyramidalis P.Beauv. (10: 19.6), Warburgia ugandensis Sprague (10: 23.1) and Dichrocephala integrifolia (L.f.) Kuntze (7 ': 26.9). There is a high diversity of the species and a wealth of indigenous traditional knowledge for contraceptives and reproductive health care. Species like Prunus africana, Warburgia ugandensis and Dichrocephala integrifolia with high percentage use values are trusted by the community and can be investigated further for contraceptive potential to confirm their efficacy.

Heavy metal contamination in urban roadside vegetables: origins, exposure pathways, and health implications

Abstract Urban agriculture along major highways often exposes food crops to heavy metal contamination, primarily from vehicular emissions. This review examines the origins, exposure pathways, and health risks associated with heavy metals in roadside vegetables. Sources include both tailpipe emissions, such as lead (Pb) and cadmium (Cd), and non-tailpipe emissions from tyre and brake wear, which release zinc (Zn) and copper (Cu). Contamination occurs through atmospheric deposition on plant surfaces and root uptake from polluted soils. A systematic synthesis of global case studies reveals alarming levels of heavy metals, often exceeding WHO/FAO thresholds. For instance, vegetables cultivated along the Accra-Tema motorway in Ghana contained cadmium levels up to 279 mg/kg, posing significant health risks. Similarly, roadside vegetables in India, Nigeria, and China demonstrated bioaccumulation of toxic elements, with health implications including carcinogenic and non-carcinogenic effects. The review highlights the direct and indirect exposure pathways for humans, such as dietary intake of contaminated vegetables, inhalation of particulates, and dermal contact. Health consequences include gastrointestinal distress, neurotoxicity, reproductive issues, and elevated cancer risks. To mitigate these risks, the review advocates for the prohibition of vegetable farming near high-traffic highways, along with the implementation of stringent monitoring programs to assess and control heavy metal levels. Future research should address ecological impacts and integrate diverse contamination sources to develop effective risk management strategies. This work is a critical resource for policymakers, researchers, and urban planners aiming to enhance food safety and public health in urban settings.

Sexual Behaviours and Reproductive Health Issues among Students in Tertiary Institutions in Delta State: Counselling Implications

The study investigated sexual behaviours and reproductive health issues among students in tertiary institutions in Delta State, and discussed their counselling implications. It addressed some relationship issues that confront students at the tertiary education level which include awareness about prventive measures against sexually transmitted infections among sexually active students; young girls resorting to unsafe abortion; high level of sexual abuse and rape; and some female students engaging in part-time prostitution, among others. The study's population consisted of 14,650 first-year students in higher educational institutions in Delta State of Nigeria. Based on willingness to participate, a purposeful sampling technique was used to select a sample size of 3,490 students. A questionnaire on Sexual Behaviour and Reproductive Health Issues (SEBARHI) was developed by the authors and used to collect data on Sexual Behaviour and Reproductive Issues among the students. Data collected was analyzed with descriptive statistics and it was found that a considerable number of undergraduates in the area of study engage in risky sexual behaviour and also demonstrated ignorance of safe reproductive health practices. More female students reported indulging in homosexuality, bisexuality, anal sex, masturbation and threesome sex, amongst others. The counselling implications of the findings of the study were discussed for increasing appropriate awareness of the consequences of risky sexual behaviours, unsafe reproductive health practices and need to seek help from professional counselling practitioners.

Evaluation of the effectiveness of Russian universities in addressing personnel development challenges

Introduction. The transition to a new system of higher education in Russia is examined within the framework of the Strategy for Scientific and Technological Development.Aim. The present research aims to analyse existing and planned university performance indicators, assess their relevance to personnel development at universities, and formulate proposals to enhance the personnel development system, taking into account the implementation of a new personnel training system in Russian higher education.Methodology and research methods. The fundamental methodological approach employed was systematic. Theoretical research methods utilised included a literature review on the research problem, analysis of normative documents, comparison and generalisation, induction, and synthesis, which involved formulating proposals for an approach to evaluating university activities.Results. An analysis of the current performance indicators of universities led the author to conclude that two indicators are prioritised: the proportion of employed graduates and the proportion of teaching staff whose average salary is 200% or more than the regional average salary. The introduction of a new indicator, which aims to characterise the system of personnel development (the share of employees under the age of 39 among the total number of scientific and pedagogical workers), may result in a reduction of teaching staff from other age groups. Based on an analysis of the trends in the number of teaching staff at leading universities in the Chelyabinsk and Sverdlovsk regions, a consistent decline in both the total number of teaching staff and the proportion of teachers under 40 years old has been observed. The issue of personnel reproduction within universities is a critical one. However, the new system of indicators for evaluating the effectiveness of universities, which will take effect on January 1, 2025, does not address this problem.Scientific novelty. The author proposes a reevaluation of the approach to financing universities, suggesting that the state should financially support the number of staff positions justified by each university. This proposal includes the establishment of salary rates for young teachers, with the estimated proportion of these rates constituting at least 35% of the total number of teaching staff positions at the university. Implementing this approach will promote continuity in the intellectual and value-based development of teaching staff, grounded in established scientific schools.Practical significance. The research findings can be used to formulate a strategy for advancing the scientific and educational sectors in light of the transition to a new personnel training system in higher education.

Exploring critical animal-based traits as potential predictors of production diseases in dairy cattle: a systematic review and meta-analysis

This meta-analysis comprehensively evaluates the impact of production diseases on dairy cattle, examining a variety of physiological, metabolic, and behavioral traits. From an initial set of 3 349 records, a rigorous selection process resulted in 56 relevant articles, highlighting the strict criteria employed. The low inclusion rate of 1.67% underscores the dedication to studying quality and significance. Common reasons for exclusion, such as statistical methodology and the lack of a negative control group, emphasize the necessity for robust scientific investigation. The study reveals key indicators of production diseases, such as decreased milk production, weight loss, a low body condition score, digestive disorders, lameness, and respiratory distress. These findings align with existing knowledge, emphasizing the multifaceted nature of production diseases and their broad impact on dairy cattle health. Diseased animals consistently exhibit higher parameter values, supported by confidence intervals that indicate result precision. Subgroup analyses offer nuanced insights into the specific effects of diseases and interventions on different characteristics. Metritis and Mastitis significantly affect milk production, highlighting the economic implications for dairy farmers. Interventions such as improved milking techniques show promise. Similarly, interventions involving veterinary medications and controlled energy diets effectively mitigate weight loss, a low body condition score, and digestive disorders. The analysis underscores the vulnerability of dairy cattle to reproductive issues, metabolic imbalances, and increased susceptibility to infections. Interventions addressing these challenges include hormone therapy, balanced diets, and vaccination programs. Behavioral changes and feeding habits emerge as significant indicators of dairy cattle well-being. Ovarian cysts are identified as a major contributor to behavioral changes, necessitating targeted interventions. In conclusion, this meta-analysis provides valuable contributions to the field of dairy cattle health, offering specific insights into the effects of diseases and the effectiveness of interventions. These findings inform evidence-based practices for dairy stakeholders, ultimately enhancing animal welfare and promoting sustainable dairy production. However, establishing precise reference values presents challenges, warranting further investigation.

Adjusting the timing of inseminations to the time lag on luteolysis alerts results in higher conception in dairy cattle

Dairy cow fertility is a complex trait that depends on the cow's physiological status, the farm's environmental and management conditions, and their interactions. Already the slightest improvement in fertility can positively impact a farm's profitability and sustainability. In research, milk progesterone (P4) has often been used as an accurate and feasible way to identify a dairy cow's reproduction status. Moreover, in Europe and Canada, it has been used to improve fertility management on commercial farms as it allows to accurately identify reproduction issues, pregnancy and the optimal insemination window. An on-farm P4 device (OPD) automatically samples, measures and monitors the milk P4 concentration of individual cows. To this end, the P4 data is smoothed to be robust for measurement errors and outliers, and fixed thresholds are used to estimate the time of luteolysis preceding ovulation, thereby generating a luteolysis alert (LA). By smoothing the P4 data, the OPD introduces a time lag on the LA. Variation in this time lag is not considered in the estimation of the optimal insemination window that is advised to the farmer. Ignoring this variation might decrease the accuracy of the optimal insemination window and, therefore, decreases the likelihood of conception. We hypothesize that considering the length of the time lag and adapting the advice accordingly improves the conception rate. This observational retrospective study uses an extensive data set from 17 commercial dairy farms that are equipped with an OPD. We estimated the time lag on the alerts and evaluated their relationship with the interval from LA to insemination for successful (n = 3721) and unsuccessful inseminations (n = 3896) separately. Results showed that the probability of conception increases when a longer LA time lag is compensated with a shorter interval from LA to insemination and vice versa. In addition, for successful inseminations, we found a clear negative relation between the time lag and the interval from LA to insemination and the interval was significantly shorter when the time lag of the LA was longer. This negative relation between time lag and interval from LA to insemination was less pronounced for unsuccessful inseminations. Additionally, we evaluated the conception rates for inseminations that are performed too early, in time or too late with respect to the optimal insemination window advised by the OPD, in function of their associated time lags. We found that, for inseminations that were preceded by a short time lag (<8 h), the conception rate was 17.5 percentage points higher when cows were inseminated later than advised. Likewise, when inseminations were preceded by a long time lag (≥24 h), we found that the conception rate was 13 percentage points higher when cows were inseminated earlier than advised. Our results suggest that farmers using an OPD could potentially increase their conception success by compensating the variable time lag on the LA by adapting the interval from alert to insemination accordingly. This could be used to develop reproductive management strategies to improve reproductive performance on those farms, which can positively impact their sustainability.

EXPLORING THE CHALLENGES AND SIGNIFICANCE OF EDUCATION FOR WOMENS EMPOWERMENT: A STUDY IN HOOGHLY DISTRICT

Education is crucial for womens welfare, progress, and empowerment. Women face discrimination from conception to death and need greater influence in all areas of life. Empowerment yields strength and leads to rural development. This article aims to study the role of education in womens empowerment inChinsurah,Hooghly District. The study examines the obstacles and challenges faced by womens empowerment in Chinsurah, Hooghly District. It uses a descriptive survey design and a questioner to collect data from both employed and unemployed women. The results show that employed women strongly agree on the importance of education, while unemployed women do not recognize this. The majority of employed women believe that economic problems can be solved through empowerment, while unemployed women accept empowerment as a solution. The study also highlights the challenges faced by women due to traditional gender roles, patriarchal systems, cultural and religious beliefs, economic challenges, educational barriers, health and reproductive issues, and technological barriers.

Thyroid Disorders in Patients with Polycystic Ovarian Syndrome in a Tertiary Care Center: An Observational study

Introduction: Polycystic ovarian syndrome is the most common endocrine and metabolic disorder in women of childbearing age, affecting 3–15% of women worldwide, leading to reproductive, metabolic, and psychological issues. Patients with polycystic ovarian syndrome require rigorous thyroid function detection, monitoring, and correction over time. In this study, we aimed to evaluate the clinical presentations and thyroid dysfunction in patients with polycystic ovarian syndrome.Methods: An observational study was done in patients with polycystic ovarian disease presenting to a tertiary care centre over six months, from December 2023 to May 2024 Total population sampling was done. All the women during the study period diagnosed with polycystic ovarian disease based on Rotterdam criteria were included in the study after getting ethical approval from the institutional review board. (Reference number: 20102023/03).Results: The mean age of women in the study was 24.74±5.01 years. A total of 28 (31.46%) patients of polycystic ovarian disease had hyperthyriodism, hypothyroidism was found in 13 (14.60%) and subclinical hypothyroidism was found in 6 (6.74%) patients. All the women had menstrual irregularities. Regarding androgenic characteristics, 53 (59.55%) of patients presented with hirsutism, 43 (48.51%) presented with acne, 13 (14.61%) women had alopecia, and 4 (4.49%) women had acanthosis.Conclusions: Hyperthyroidism, hypothyroidism and subclinical hypothyroidism were prevalent in polycystic ovarian disease patients, emphasizing the need for thorough thyroid evaluation in polycystic ovarian disease patients due to its impact on metabolic and reproductive health. High rates of menstrual irregularities, androgenic symptoms like hirsutism and acne, and fertility challenges were also prevalent, aligning with findings from similar studies.

Lycopene's therapeutic mechanisms in epididymitis: a network pharmacology and experimental study.

Epididymitis, a common disease of the male reproductive system, is often caused by nonspecific infections. Antibiotics alone cannot reverse histopathological changes or prevent long-term reproductive issues. Lycopene (LYC), a potent antioxidant, has shown potential in alleviating epididymitis, yet its specific mechanisms remain unclear. This study used network pharmacology and in vivo experiments to explore LYC's mechanisms in treating epididymitis. Epididymitis- and LYC-related target proteins were identified from multiple databases and analyzed using the Venny platform. Protein interactions were examined with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and key targets were identified via topological analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using the Database for Annotation, Visualization and Integrated Discovery (DAVID) database. Target-pathway networks were visualized in Cytoscape, molecular docking was performed with AutoDock Vina, and LYC's effects were validated in a lipopolysaccharide (LPS)-induced epididymitis mouse model. Network pharmacology results indicated that LYC's effects involve the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, which plays a crucial role in regulating inflammation and apoptosis. In vivo, LYC improved epididymal pathology, reduced inflammatory cell infiltration, and decreased key inflammatory cytokines, including interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). By inhibiting PI3K/AKT activation, LYC modulated inflammation and reduced apoptosis. Additionally, LYC enhanced antioxidant enzyme activity and elevated the B-cell lymphoma-extra large (Bcl-xL) ratio, reducing oxidative stress and apoptosis. Molecular docking supported these findings, showing strong binding affinities with PI3K/AKT pathway targets. This study highlights LYC's potential as an adjunctive treatment for epididymitis, targeting inflammation and oxidative stress via the PI3K/AKT pathway. These findings suggest that LYC could enhance current therapies and provide new options for the clinical management of epididymitis.

Structure-Activity Relationships and Discovery of (S)-5-(tert-Butyl)-11-(difluoromethoxy)-9-methoxy-2-oxo-1,2,5,6-tetrahydropyrido[2',1':2,3]imidazo[4,5-h]quinoline-3-carboxylic Acid (AB-161), a Novel Orally Available and Liver-Centric HBV RNA Destabilizer.

Lowering hepatitis B surface antigen (HBsAg) levels from covalently closed circular DNA (cccDNA) and the integrated genome could reduce the persistence of hepatitis B virus (HBV) infection. Since HBV replication occurs in the liver and to ameliorate the peripheral neuropathy observed with a first-generation tricyclic 4-pyridone PAPD5/7 inhibitor (AB-452) having high systemic exposure, we focused on increasing the hepatocyte concentration and reducing plasma levels. Optimization of a novel series of PAPD5/7 inhibitors that decrease HBsAg levels led to the tetracyclic 2-pyridone AB-161, which was similarly potent to AB-452 in vitro and in vivo but showed dramatically higher rodent liver-to-plasma ratios. There were no neurobehavioral effects with AB-161 in dogs up to 45 mg/kg after 60 days, unlike with AB-452, where these were observed at lower doses by day 14. AB-161 was then advanced into 90-day GLP toxicology studies, where the improved neurotoxicity profile persisted, but reproductive issues emerged, leading to discontinuation.

Infrared Thermography: A Non-Invasive Way to Assess Animal Health and Productivity

Abstract Dairy cattle may experience stress and anxiety due to rough handling by humans, extreme weather conditions, change in feed, social grouping, transportation, and limited access to pasture. Stress is the body’s response to a threat, while anxiety is persistent stress that impacts physical and psychological health. Cows experiencing consistent stress or anxiety tend to eat less, produce less milk, have reproductive issues, change in milk composition, spend more time being vigilant and are more prone to illness and mortality. Infrared thermography (IRT) detects temperature changes in an animal’s body caused by stress or anxiety. It measures heat radiation emitted from the body’s surface using an infrared sensor from a distance. Studies have shown that IRT of the eyes has the potential to automate the assessment of cow health, monitor changes in milk composition, and differentiate between sick and healthy animals, unlike rectal temperature recording, behavioural assessment, and milk composition tests. IRT of the eyes was found to be repeatable and positively correlated with rectal temperature, unlike rectal temperature measurements, which were found to be non-reproducible. Further research and refinement of IRT of the eyes could improve automated cow health monitoring and management. Information © The Author 2024

Assessing the effects of cadmium on antioxidant enzymes and histological structures in rainbow trout liver and kidney

Cadmium contamination in aquatic environments poses severe risks to aquatic organisms, particularly fish, where cadmium accumulation in tissues can lead to compromised organ functionality and reproductive issues. The present study aimed to assess the effects of cadmium (Cd) exposure on key biomarkers of oxidative stress, DNA damage, apoptosis, and enzyme activity in the liver and kidney tissues of rainbow trout (Oncorhynchus mykiss). Specifically, the study measured 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, caspase-3 activation, acetylcholinesterase (AChE) activity, and oxidative stress indicators (ONOO−, MDA, GSH, SOD, and CAT) following exposure to three Cd concentrations (1, 3, and 5 mg/L) over three time points (24, 48, and 96 h). Tissue samples were collected post-exposure, and the analysis revealed a significant decrease in MDA levels in both tissues. GSH concentrations declined with prolonged exposure, while SOD activity increased, indicating a response to oxidative stress, contrasted by a reduction in CAT activity. An initial increase in ONOO− levels was observed at 24 h, followed by a subsequent decrease at the 48 and 96 h marks. These results suggest that cadmium induces oxidative stress in the liver and kidney tissues of fish. Cadmium exposure also significantly elevated 8-OHdG levels, signaling DNA damage, and increased caspase-3 activity, indicative of apoptosis, across all doses and time points (p < 0.05). The histological examination of liver and kidney showed tissue injury. Additionally, a negative correlation between AChE activity and exposure duration was noted, with prolonged exposure resulting in substantial AChE inhibition. Given the role of AChE in behavior regulation, these findings underscore the importance of exploring time-dependent, tissue-specific changes in AChE activity to further elucidate the mechanisms underlying cadmium-induced behavioral abnormalities.