Ginkgolic acid inhibits the expression of SAE1 and induces ferroptosis to exert an anti-hepatic fibrosis effect.

BACKGROUND: Finding a drug for early intervention in the hepatic fibrosis process has important clinical significance. Previous studies have suggested SUMOylation as a potential target for intervention in hepatic fibrosis. However, the role of SAE1, a marker of SUMOylation, in hepatic fibrosis is unknown. Additionally, whether ginkgolic acid (GA), a SUMOylation inhibitor, inhibits hepatic fibrosis by inhibiting SUMO1-activating enzyme subunit 1 (SAE1) should be further investigated. METHODS: Liver tissues of patients with hepatic cirrhosis and a rat model of hepatic fibrosis constructed with CCl4 (400 mg/kg, twice weekly) or TAA (200 mg/kg, twice weekly) were selected, and the degree of hepatic fibrosis was then evaluated using H&E, Sirius red, and Masson's trichrome staining. After knockdown or overexpression of SAE1 in hepatic stellate cells, the expression levels of ferroptosis and hepatic fibrosis markers were measured in vitro. After intervention with a ferroptosis inhibitor, the expression levels were again measured in vivo and in vitro. RESULTS: We first demonstrated that SAE1 increased in patients with hepatic cirrhosis. Subsequently, testing of the rat hepatic fibrosis model confirmed that GA reduced the expression of SAE1 and improved hepatic fibrosis in rats. Then, we used hepatic stellate cell lines to confirm in vitro that GA inhibited SAE1 expression and induced ferroptosis, and that overexpression of SAE1 or inhibition of ferroptosis reversed this process. Finally, we confirmed in vivo that GA induced ferroptosis and alleviated the progression of hepatic fibrosis, while inhibiting ferroptosis also reversed the progression of hepatic fibrosis in rats. CONCLUSION: SAE1 is a potential anti-fibrotic target protein, and GA induces ferroptosis of hepatic stellate cells by targeting SAE1 to exert an anti-hepatic fibrosis effect, which lays an experimental foundation for the future clinical application of its anti-hepatic fibrosis effect.

Antibiotic Treatment Decrease the Fitness of Honeybee (Apis mellifera) Larvae.

Symbiotic bacteria could increase the nutrient provision, regulate the physiological state, and promote immunity in their insect host. Honeybee larvae harbor plenty of bacteria in their gut, but their functions are not well studied. To determine their effect on honeybee larvae, the 1-day-old larvae were grafted on to 24-well plates from the comb and artificially reared in the lab. They were treated with penicillin-streptomycin to remove the gut symbiotic bacteria. Then, the 5-day-old larvae and the newly emerged adults were weighted. The developmental periods to pupae and eclosion were investigated, respectively. The bacterial amount, expression of developmental regulation genes (ecr and usp), nutrient metabolism genes (ilp1, ilp2, hex 70a, hex 70b, hex 70c, and hex 110), and immunity genes (apidaecin, abaecin, defensin-1, and hymenoptaecin) were determined by qRT-PCR. The result showed that the antibiotics-treated larvae have significantly lower body weights in the 5-day-old larvae and the emerged bees. The expression of ilp2 and hex 70c in 5-day-old larvae was down-regulated. The usp was down-regulated in 5-day-old larvae, but increased in 7-day-old larvae, which disturbed the normal developmental process and caused the extension of eclosion. Moreover, antibiotics treatment significantly decreased the expression of apidaecin and abaecin in 5-day-old larvae, and defensin-1 and hymenoptaecin in 7-day-old larvae, respectively. These results showed that antibiotics could weaken the nutrient metabolism, disturb the development process, and decrease the immune competence of honeybee larvae, indicating the vital roles of gut bacteria in bee larvae fitness, so the antibiotics should be avoided to control microbial disease in honeybee larvae.

Pollen reverses decreased lifespan, altered nutritional metabolism and suppressed immunity in honey bees (Apis mellifera) treated with antibiotics.

Nutrition is involved in regulating multiple aspects of honey bee biology such as caste, immunity, lifespan, growth and behavioral development. Deformed wing virus (DWV) is a major pathogenic factor which threatens honey bee populations, and its replication is regulated by the nutrition status and immune response of honey bees. The alimentary canal of the honey bee is home to a diverse microbial community that provides essential nutrients and serves to bolster immune responses. However, to what extent gut bacteria affect honey bee nutrition metabolism and immunity with respect to DWV has not been investigated fully. In this study, newly emerged worker bees were subjected to four diets that contained (1) pollen, (2) pollen and antibiotics, (3) neither pollen nor antibiotics or (4) antibiotics alone. The expression level of two nutrition genes target of rapamycin (tor) and insulin like peptide (ilp1), one nutritional marker gene vitellogenin (vg), five major royal jellyprotein genes (mrjp1-5), one antimicrobial peptide regulating gene relish (rel), and DWV virus titer and its replication intermediate, negative RNA strand, were determined by qRT-PCR from the honey bees at 7 days post-antibiotic treatment. Additionally, honey bee head mass and survival rate were measured. We observed that antibiotics decreased the expression of tor and rel, and increased DWV titer and its replication activity. Expression of ilp1, mrjp1-5 and vg, and honey bee head mass were also reduced compared with bees on a pollen diet. Antibiotics also caused a significant drop in survivorship, which could be rescued by addition of pollen to the diet. Of importance, pollen could partially rescue the loss of vg and mrjp2 while also increasing the head mass of antibiotic-treated bees. Our results illuminate the roles of bacteria in honey bee nutrition, metabolism and immunity, which confer the ability to inhibit virus replication, extend honey bee lifespan and improve overall health.

Indigenous HIV Prevention Beliefs and Practices Among Low-Earning Chinese Sex Workers as Context for Introducing Female Condoms and Other Novel Prevention Options.

New interventions to reduce HIV and sexually transmitted infections (STI) among female sex workers are introduced into the context of women's existing prevention beliefs and practices. These indigenous practices affected implementation of our program to introduce female condoms to women in sex-work establishments in southern China. We used ethnographic field observations and in-depth interviews to document common prevention methods women reported using to protect themselves before and during intervention implementation. Individual, sex-work establishment, and other contextual factors, including sources of information and social and economic pressures to use or reject prevention options, shaped their perceptions and selection of these methods and affected adoption of female condoms as an additional tool. Efforts to improve uptake of effective prevention methods among low-income sex workers require attention to the context and spectrum of women's HIV/STI prevention practices when introducing innovations such as female condoms, microbicides, pre-exposure prophylaxis pills, and others, as they become available.

Efficacy and safety of traditional Chinese medicine for the treatment of influenza A (H1N1): A meta-analysis.

BACKGROUND: In March 2009, the first reported case infected with influenza A (H1N1) virus was identified in Mexico. The World Health Organization officially declared the outbreak to be a pandemic on June 11, 2009. The objective of this study was to evaluate the efficacy and safety of traditional Chinese medicine (TCM) in the treatment of influenza A (H1N1) infection. METHODS: We electronically and manually searched electronic databases, reference lists, and conference compilations to identify randomized clinical trials that compared the treatment of influenza A (H1N1) using TCM with a control group receiving oseltamivir or antivirus therapy. The Jadad score was used to assess trial quality. Duration of viral shedding, time to defervescence, and effective rate were taken as outcome measurements; additionally, heterogeneity analysis and meta-analysis were performed. RESULTS: A total of 30 studies were included in our investigation, and these studies together included 3444 cases. Based on the Jadad score, each of these studies were divided as follows: high-quality studies (n = 3), medium-quality studies (n = 2), and low quality studies (n = 25). A meta analysis was performed, which indicated that the time to defervescence between the TCM treatment group and the control group was statistically significant, the duration of viral [Influenza A (H1N1)] shedding in the integrated Chinese and Western medicine subgroups was statistically significant, but it was not statistically significant between the two groups, the effective rate between the two groups was not statistically significant. A total of 18 studies described adverse drug reactions. CONCLUSION: The results of our study indicated that the mean time to defervescence in the TCM treatment group was less than noted in the control group, and that the duration of viral [Influenza A (H1N1)] shedding in the integrated Chinese and Western medicine subgroups was less than that noted in the control group. However, the available evidence does not consider the fact that the difference in duration of viral shedding and effective rate between the two groups was statistically similar. No obvious adverse events were reported in the included studies.

A systematic review of factors influencing fertility desires and intentions among people living with HIV/AIDS: implications for policy and service delivery.

With availability of antiretroviral treatments, HIV is increasingly recognised as a chronic disease people live with for many years. This paper critically reviews the current literature on fertility desires and reproductive intentions among people living with HIV/AIDS (PLHIV) and critiques the theoretical frameworks and methodologies used. A systematic review was conducted using electronic databases: ISI Web of Knowledge, Science Direct, Proquest, Jstor and CINAHL for articles published between 1990 and 2008. The search terms used were fertility desire, pregnancy, HIV, reproductive decision making, reproductive intentions, motherhood, fatherhood and parenthood. Twenty-nine studies were reviewed. Fertility desires were influenced by a myriad of demographic, health, stigma-associated and psychosocial factors. Cultural factors were also important, particularly in Sub-Saharan Africa and Asia. Future research that examines fertility desires among PLHIV should include cultural beliefs and practices in the theoretical framework in order to provide a holistic understanding and to enable development of services that meet the reproductive needs of PLHIV.