Curcumin protects against cadmium-induced germ cell death in the testis of rats.

Introduction: Cadmium (Cd) has been shown to disrupt the reproductive system. In this study, we evaluated the protective effects of Curcumin (Cur) against Cd-induced reproductive toxicity. Methods: Exploring the role of Cur in Cd-treated rat models. Results: The study demonstrated that Cd treatment impaired the seminiferous epithelium, leading to increased apoptosis of germ cells. Interestingly, pretreatment with Cur ameliorated the histological damage and decreased the germ cell apoptosis induced by Cd. Furthermore, after Cd exposure, B-cell lymphoma-2 expression was significantly decreased while Bax expression was increased. Pretreatment of rats with Cur protected against germ cell apoptosis by improving the expression of B-cell lymphoma-2 and reducing Bax. Additionally, Cd treatment increased reactive oxygen species, resulting in a decrease in antioxidant enzymes. However, pretreatment of rats with Cur followed by Cd administration led to a substantial decrease in reactive oxygen species levels and increased activities of antioxidant enzymes. Ultrastructural investigations revealed that damage to the mitochondrial structure was significantly ameliorated by Cur pretreatment in Cd-treated rats. Notably, Cur significantly activated the peroxisome proliferator-activated receptor gamma coactivator 1a/Sirtuins-3 signaling pathway. Conclusions: Overall, our data suggest that Cd induces germ cell apoptosis through mitochondrial-induced oxidative stress, but Cur pretreatment offers strong protection against Cd-induced reproductive toxicity.

Association Between the Hepatic Steatosis Index and Risk of Incident Type 2 Diabetes Mellitus in the Normoglycemic Population:A Longitudinal Prospective Study in Japan.

Purpose: The Hepatic Steatosis Index (HSI) is a reliable predictor of non-alcoholic fatty liver disease (NAFLD), which can increase the risk of type 2 diabetes mellitus (T2DM). However, limited research has directly predicted HSI's association with T2DM occurrence at normal blood glucose levels. Hence, this study aimed to assess the link between baseline HSI and T2DM development under euglycemic conditions while also exploring potential sex differences. Methods: Using data from the NAGALA cohort study, a Cox regression model analyzed the relationship between HSI and T2DM risk, calculating hazard ratios (HR) and 95% confidence intervals (CI). Subgroup analyses were conducted to investigate factors influencing HSI's prediction of incident T2DM. Results: During a mean 6.1-year follow-up, 238 individuals (1.65% of participants) developed T2DM. After adjusting for age, ethanol consumption, smoking status, SBP, DBP, TG, and TC, HSI showed a significant association with incident T2DM in individuals with normal glucose levels, consistent across sexes. Compared to the lowest quartile group (Q1), the HR and 95% CI for Q2, Q3, and Q4 were 1.09 (0.61, 1.93), 1.16 (0.68, 1.98), and 3.30 (2.04, 5.33), respectively (P for trend < 0.001). Subgroup analysis indicated that elevated HSI significantly increased the risk of incident T2DM in individuals with normal TG levels (P for interaction = 0.0170). Conclusion: This study highlights the significant association between elevated HSI levels and the likelihood of developing incident T2DM in individuals with normal glucose levels. Furthermore, it offers a simple and valuable screening tool for predicting T2DM.

Intraoperative Intraocular Lens Waste: Incidence, Cost and Reasons.

PURPOSE: To evaluate the incidence and cost of intraocular lens(IOL) waste during IOL implantation, as well as the reasons for it. METHODS: A retrospective analysis was conducted on the data of 485 patients from the IOL waste registers of a single tertiary eye hospital in China during 2016-2020. The primary outcomes were the incidence, cost, and reasons for different IOL properties. Cases were examined to ascertain IOL material, design, procedural details, and causes of waste. RESULTS: IOL waste occurred in 485 (6.62‰) of the 73,246 IOL implantations during the study period. The total cost of IOL waste was 429, 850.26 Chinese Yuan (CNY) related to waste with an average cost of 2, 442.33 CNY per procedure during the study period. Comparisons between IOL properties showed that polymethyl methacrylate (PMMA) material (39, 2.05%), three-piece design (142, 1.49%), and secondary IOL implantation (26, 2.16%) were associated with IOL wastage, and the difference was statistically significant. The causes of IOL waste were damage (107, 60.80%), patient reasons (37, 21.26%), aseptic errors (22, 12.50%), IOL quality problems (8, 4.55%), and loss (2, 1.14%). CONCLUSIONS: The incidence of IOL waste is low, but still leads to a significant cost burden due to a large number of cataract surgeries. PMMA material, three-piece design, and secondary implantation were identified as factors increasing IOL waste. Damage emerged as the primary reason for waste, largely attributed to human error. Therefore, the development of strategies to mitigate IOL waste is imperative.

Prelimbic cortex-nucleus accumbens core projection positively regulates itch and itch-related aversion.

Itch is one of the most common clinical symptoms in patients with diseases of the skin, liver, or kidney, and it strongly triggers aversive emotion and scratching behavior. Previous studies have confirmed the role of the prelimbic cortex (Prl) and the nucleus accumbens core (NAcC), which are reward and motivation regulatory centers, in the regulation of itch. However, it is currently unclear whether the Prl-NAcC projection, an important pathway connecting these two brain regions, is involved in the regulation of itch and its associated negative emotions. In this study, rat models of acute neck and cheek itch were established by subcutaneous injection of 5-HT, compound 48/80, or chloroquine. Immunofluorescence experiments determined that the number of c-Fos-immunopositive neurons in the Prl increased during acute itch. Chemogenetic inhibition of Prl glutamatergic neurons or Prl-NAcC glutamatergic projections can inhibit both histaminergic and nonhistaminergic itch-scratching behaviors and rectify the itch-related conditioned place aversion (CPA) behavior associated with nonhistaminergic itch. The Prl-NAcC projection may play an important role in the positive regulation of itch-scratching behavior by mediating the negative emotions related to itch.

Cross-talk between Vimentin and autophagy regulates blood-testis barrier disruption induced by cadmium.

The blood-testis barrier (BTB) plays a vital role in mammalian spermatogenesis by separating the seminiferous epithelium into an adluminal and a basal compartment. Cadmium (Cd) is a toxic heavy metal that is widely present in the environment. We observed that Cd can induce BTB disruption, leading to apoptosis of testicular cells. However, the molecular mechanisms contributing to BTB injury induced by Cd have not yet been fully clarified. Vimentin (Vim) is an important desmosome-like junction protein that mediates robust adhesion in the BTB. In this study, we investigated how Vim responds to Cd. We found that Cd treatment led to a significant decrease in Vim expression, accompanied by a marked increase in LC3-II expression and a higer number of autophagosomes. Interestingly, we also observed that Cd-induced autophagy was associated with decreased Vim activity and enhanced apoptosis of testicular cells. To further investigate the role of autophagy in Vim regulation under Cd exposure, we treated cells with an autophagy inhibitor called 3-MA. We found that 3-MA treatment enhanced Vim expression and improved the disruption of the BTB under Cd exposure. Additionally, the inhibition of Vim confirmed the role of autophagy in modulating Vim expression. These results reveal a previously unknown regulatory mechanism of Cd involving the interplay between a heavy metal and a protein.

Bifunctional drug delivery system with carbonic anhydrase IX targeting and glutathione-responsivity driven by host-guest amphiphiles for effective tumor therapy.

It remains a critical issue to deliver anticancer drugs to tumor tissues and reducing the toxic effects on normal tissues. The drug delivery system (DDS) based on self-assembly provides a multi-functional way for drug delivery. In this work, a supramolecular host (L-CD) with targeting function based on a ß-cyclodextrin (ß-CD) backbone was synthesized with carbonic anhydrase IX (CAIX) overexpressed on tumor cells as a target, and the methotrexate prodrug (MTX-SS-Ad) modified by adamantane and disulfide bond was prepared to be used as the guest. The amphiphilic complex was prepared between L-CD and MTX-SS-Ad through host-guest interactions and could further self-assemble into supramolecular nanoparticles (SNPs) with active targeting and stimulus release functions. The interaction between host and guest was investigated by UV, NMR, IR, XRD and TGA. The characteristic of SNPs was observed by DLS and TEM. Throng the study of molecular docking, in vitro inhibition, cell uptake experiments, and western blotting, SNPs have showed CAIX inhibitory effects both inside and outside the cells. The in vitro release experiments indicated that SNPs can undergo disintegration and release drugs under acidic and GSH conditions. Moreover, SNP can effectively inhibit the proliferation of cancer cells without generating additional toxic side effects on normal cells. So, we provide a strategy of bifunctional drug delivery system with targeting and glutathione-responsivity for effective tumor therapy.