Transcriptional Responses of Resistant and Susceptible Fish Clones to the Bacterial Pathogen Flavobacterium psychrophilum

Flavobacterium psychrophilum is a bacterial species that represents one of the most important pathogens for aquaculture worldwide, especially for salmonids. To gain insights into the genetic basis of the natural resistance to F. psychrophilum, we selected homozygous clones of rainbow trout with contrasted susceptibility to the infection. We compared the transcriptional response to the bacteria in the pronephros of a susceptible and a resistant line by micro-array analysis five days after infection. While the basal transcriptome of healthy fish was significantly different in the resistant and susceptible lines, the transcriptome modifications induced by the bacteria involved essentially the same genes and pathways. The response to F. psychrophilum involved antimicrobial peptides, complement, and a number of enzymes and chemokines. The matrix metalloproteases mmp9 and mmp13 were among the most highly induced genes in both genetic backgrounds. Key genes of both pro- and anti-inflammatory response such as IL1 and IL10, were up-regulated with a greater magnitude in susceptible animals where the bacterial load was also much higher. While higher resistance to F. psychrophilum does not seem to be based on extensive differences in the orientation of the immune response, several genes including complement C3 showed stronger induction in the resistant fish. They may be important for the variation of susceptibility to the infection

Reactive oxygen species and male reproductive hormones

Reports of the increasing incidence of male infertility paired with decreasing semen quality have triggered studies on the effects of lifestyle and environmental factors on the male reproductive potential. There are numerous exogenous and endogenous factors that are able to induce excessive production of reactive oxygen species (ROS) beyond that of cellular antioxidant capacity, thus causing oxidative stress. In turn, oxidative stress negatively affects male reproductive functions and may induce infertility either directly or indirectly by affecting the hypothalamus-pituitary-gonadal (HPG) axis and/or disrupting its crosstalk with other hormonal axes. This review discusses the important exogenous and endogenous factors leading to the generation of ROS in different parts of the male reproductive tract. It also highlights the negative impact of oxidative stress on the regulation and cross-talk between the reproductive hormones. It further describes the mechanism of ROS-induced derangement of male reproductive hormonal profiles that could ultimately lead to male infertility. An understanding of the disruptive effects of ROS on male reproductive hormones would encourage further investigations directed towards the prevention of ROS-mediated hormonal imbalances, which in turn could help in the management of male infertility

Global, regional, and national incidence of six major immune-mediated inflammatory diseases: findings from the global burden of disease study 2019

Background The causes for immune-mediated inflammatory diseases (IMIDs) are diverse and the incidence trends of IMIDs from specific causes are rarely studied. The study aims to investigate the pattern and trend of IMIDs from 1990 to 2019. Methods We collected detailed information on six major causes of IMIDs, including asthma, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, psoriasis, and atopic dermatitis, between 1990 and 2019, derived from the Global Burden of Disease study in 2019. The average annual percent change (AAPC) in number of incidents and age standardized incidence rate (ASR) on IMIDs, by sex, age, region, and causes, were calculated to quantify the temporal trends. Findings In 2019, rheumatoid arthritis, atopic dermatitis, asthma, multiple sclerosis, psoriasis, inflammatory bowel disease accounted 1.59%, 36.17%, 54.71%, 0.09%, 6.84%, 0.60% of overall new IMIDs cases, respectively. The ASR of IMIDs showed substantial regional and global variation with the highest in High SDI region, High-income North America, and United States of America. Throughout human lifespan, the age distribution of incident cases from six IMIDs was quite different. Globally, incident cases of IMIDs increased with an AAPC of 0.68 and the ASR decreased with an AAPC of −0.34 from 1990 to 2019. The incident cases increased across six IMIDs, the ASR of rheumatoid arthritis increased (0.21, 95% CI 0.18, 0.25), while the ASR of asthma (AAPC = −0.41), inflammatory bowel disease (AAPC = −0.72), multiple sclerosis (AAPC = −0.26), psoriasis (AAPC = −0.77), and atopic dermatitis (AAPC = −0.15) decreased. The ASR of overall and six individual IMID increased with SDI at regional and global level. Countries with higher ASR in 1990 experienced a more rapid decrease in ASR. Interpretation The incidence patterns of IMIDs varied considerably across the world. Innovative prevention and integrative management strategy are urgently needed to mitigate the increasing ASR of rheumatoid arthritis and upsurging new cases of other five IMIDs, respectively. Funding The Global Burden of Disease Study is funded by the Bill and Melinda Gates Foundation. The project funded by Scientific Research Fund of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (2022QN38)

Multi-variable approach to groundwater vulnerability elucidation: A risk-based multi-objective optimisation model

Groundwater vulnerability mapping is essential in environmental management strategies since there is an increase in contamination caused by excessive population growth. However, to our knowledge, there is rare research dedicated to optimizing the groundwater vulnerability models, considering risk conditions, using a robust multi-objective optimization algorithm coupled with a multi-criteria decision-making model (MCDM). This study filled this knowledge gap by developing an innovative hybrid risk-based multi-objective optimization model using three distinguished models. The first model generated two series of scenarios for rate modifications associated with two common contaminations, Nitrate and Sulfate, based on susceptibility index (SI) and DRASTICA models. The second model was a multi-objective optimization framework using non-dominated sorting genetic algorithms- II and III (NSGA-II and NSGA-III), considering uncertainties in the input rates by the conditional value-at-risk (CVaR) technique. Finally, the third model was a well-known MCDM model, the COmplex PRoportional ASsessment (COPRAS), which identified the best compromise solution among Pareto-optimal solutions for weights of the contaminations. Regarding the Sulfate’s results, although the optimized DRASTICA model led to the same correlation as the initial model, 0.7, the optimized SI model increased the correlation to 0.8 compared to the initial model as 0.58. For the Nitrate, both the optimized SI and the optimized DRASTICA models raised the correlation to 0.6 and 0.7 compared to the initial model with a correlation value of 0.36, respectively. Hence, the best and the lowest correlation among the optimized models were between SI and Sulfate concentration and SI and Nitrate concentration, respectively

Transplantation of differentiated umbilical cord mesenchymal cells under kidney capsule for control of type I diabetes in rat

Nowadays, stem cells have been introduced as an appropriate source of regenerative medicine for treatment of type I diabetes. Human umbilical cord matrix-derived mesenchymal cells (hUCMC) have successfully been differentiated into insulin producing cells. The isolated hUCM cells were characterized by the expression of stem cell surface markers and by differentiation into adipocytes and osteocytes. The hUCMCs were cultured with different concentrations of neural conditional medium (NCM) and were induced to differentiate into insulin producing cells (IPCs). As 60% NCM concentration resulted in higher nestin and PDX1 expression, the cells were first exposed to 60% NCM and were then induced for IPCs differentiation. PDX1 and insulin gene expression was evaluated in the treated cells. Also, the secretion capacity of the IPCs was assessed by glucose challenge test. IPCs were transferred under the rat kidney capsule. Blood glucose level, weight gain and immunohistochemistry assessments were done in the treated animals. hUCMC expressed mesenchymal cell surface markers and successfully differentiated into adipocytes and osteocytes. Higher NCM concentration resulted in higher PDX1 and nestin expression. The IPCs expressed insulin and PDX1. IPCs were detectable under the kidney capsule 2 months after injection. IPCs transplantation resulted in a sharp decline of blood sugar level and less weight loss. Differentiated hUCM cells could alleviate the insulin deprivation in the rat model of type I diabetes. In addition, higher NCM concentration leads to more differentiation into IPCs and more nestin and PDX1 expression. Kidney capsule can serve as a suitable nominee for IPCs transplantation

Anti-viral effect of methanolic extract of Sea cucumber on HIV-1 virus

Background and Objective: Sea cucumber (Holothuria leucospilota) is used for food purposes and traditional medicine in the South East and East Asia. This study was done to determine the antiviral effect of methanolic extract, of Holothuria leucospilota species against HIV-1 virus. Methods: In this laboratory study, sea cucumbers were collected from Larak Island, Persian Gulf, Iran at depths of 10-30 m. Methanol solvent was used for extraction process. Extract was concentrated by rotary evaporator at 40-45 degree C, and subsequently was prepared in the form of dry powder using vacuum freeze dryer lyophilization. Results: The extract in 100 and 1000 µg/ml of concentrations inhibited by 94% and 92.5% the replication of HIV-1, respectively. 10 µg/ml of extract had not specific antiviral effect. Approximately the half of concentration of extract (35.89 µg/ml) prevents 50% of proliferation of HIV-1, which was 50% toxic of on host cells (P<0.05). Conclusion: Sea cucumber methanolic body wall extract of Holothuria leucospilota species had no antiviral effect against HIV-1 virus. It can be due to cytotoxic effect of extract on the host cells