Improving precision management of anxiety disorders: a Mendelian randomization study targeting specific gut microbiota and associated metabolites.

Background: There is growing evidence of associations between the gut microbiota and anxiety disorders, where changes in gut microbiotas may affect brain function and behavior via the microbiota-gut-brain axis. However, population-level studies offering a higher level of evidence for causality are lacking. Our aim was to investigate the specific gut microbiota and associated metabolites that are closely related to anxiety disorders to provide mechanistic insights and novel management perspectives for anxiety disorders. Method: This study used summary-level data from publicly available Genome-Wide Association Studies (GWAS) for 119 bacterial genera and the phenotype "All anxiety disorders" to reveal the causal effects of gut microbiota on anxiety disorders and identify specific bacterial genera associated with anxiety disorders. A two-sample, bidirectional Mendelian randomization (MR) design was deployed, followed by comprehensive sensitivity analyses to validate the robustness of results. We further conducted multivariable MR (MVMR) analysis to investigate the potential impact of neurotransmitter-associated metabolites, bacteria-associated dietary patterns, drug use or alcohol consumption, and lifestyle factors such as smoking and physical activity on the observed associations. Results: Bidirectional MR analysis identified three bacterial genera causally related to anxiety disorders: the genus Eubacterium nodatum group and genus Ruminococcaceae UCG011 were protective, while the genus Ruminococcaceae UCG011 was associated with an increased risk of anxiety disorders. Further MVMR suggested that a metabolite-dependent mechanism, primarily driven by tryptophan, tyrosine, phenylalanine, glycine and cortisol, which is consistent with previous research findings, probably played a significant role in mediating the effects of these bacterial genera to anxiety disorders. Furthermore, modifying dietary pattern such as salt, sugar and processed meat intake, and adjusting smoking state and physical activity levels, appears to be the effective approaches for targeting specific gut microbiota to manage anxiety disorders. Conclusion: Our findings offer potential avenues for developing precise and effective management approaches for anxiety disorders by targeting specific gut microbiota and associated metabolites.

Impact of antioxidants on PM2.5 oxidative potential, radical level, and cytotoxicity.

Antioxidants are typically seen as agents that mitigate environmental health risks due to their ability to scavenge free radicals. However, our research presents a paradox where these molecules, particularly those within lung fluid, act as prooxidants in the presence of airborne particulate matter (PM2.5), thus enhancing PM2.5 oxidative potential (OP). In our study, we examined a range of antioxidants found in the respiratory system (e.g., vitamin C, glutathione (GSH), and N-acetylcysteine (NAC)), in plasma (vitamin A, vitamin E, and ß-carotene), and in food (tert-butylhydroquinone (TBHQ)). We aimed to explore antioxidants' prooxidant and antioxidant interactions with PM2.5 and the resulting OP and cytotoxicity. We employed OH generation assays and electron paramagnetic resonance assays to assess the pro-oxidative and anti-oxidative effects of antioxidants. Additionally, we assessed cytotoxicity interaction using a Chinese hamster ovary cell cytotoxicity assay. Our findings revealed that, in the presence of PM2.5, all antioxidants except vitamin E significantly increased the PM2.5 OP by generating more OH radicals (OH generation rate: 0.16-24.67 pmol·min-1·m-3). However, it's noteworthy that these generated OH radicals were at least partially neutralized by the antioxidants themselves. Among the pro-oxidative antioxidants, vitamin A, ß-carotene, and TBHQ showed the least ability to quench these radicals, consistent with their observed impact in enhancing PM2.5 cytotoxicity (PM2.5 LC50 reduced to 91.2 %, 88.8 %, and 75.1 % of PM2.5's original level, respectively). Notably, vitamin A and TBHQ-enhanced PM2.5 OP were strongly associated with the presence of metals and organic compounds, particularly with copper (Cu) contributing significantly (35 %) to TBHQ's pro-oxidative effect. Our study underscores the potential health risks associated with the interaction between antioxidants and ambient pollutants.

Characterization and hypoglycemic effects of sulfated polysaccharides derived from brown seaweed Undaria pinnatifida.

The brown seaweed Undaria pinnatifida polysaccharides show various biological activities, but their hypoglycemic activity and the underlying mechanism remain unclear. Here, three fractions of sulfated polysaccharides Up-3, Up-4, and Up-5 were prepared by microwave-assisted extraction from U. pinnatifida. In vitro assays demonstrated that Up-3 and Up-4 had strong α-glucosidase inhibitory activity, and Up-3, Up-4, and Up-5 could improve the glucose uptake in insulin-resistant HepG2 cells without affecting their viability. In vivo studies indicated Up-3 and Up-4 markedly reduced postprandial blood glucose levels. Up-U (a mixture of Up-3, Up-4, and Up-5), reduced fasting blood glucose levels, increased glucose tolerance and alleviated insulin resistance in HFD/STZ-induced hyperglycemic mice. Histopathological observation and hepatic glycogen measurement showed that Up-U alleviated the damage of the pancreas islet cell, reduced hepatic steatosis, and promoted hepatic glycogen synthesis. These findings suggest that Up-U could alleviate postprandial and HFD/STZ-induced hyperglycemia and was a potential agent for diabetes treatment.

The comparative toxicities of BPA, BPB, BPS, BPF, and BPAF on the reproductive neuroendocrine system of zebrafish embryos and its mechanisms.

Bisphenol A (BPA) is a well-known endocrine disruptor that has elicited great concern because of its potential toxic effects in organisms. In this study, the effects of BPA and several BPA structural analogs, including BPB, BPS, BPF, and BPAF, on the reproductive neuroendocrine system were evaluated during zebrafish embryonic and larval development. Our results showed that the numbers of gonadotropin-releasing hormone 3 neurons in zebrafish embryos increased after 100 µg/L BPA analog treatment, and exposure to BPA or its analogs at 1 or 100 µg/L increased the expression of reproductive neuroendocrine-related genes and the levels of typical hormones such as LH, FSH, E2, and GH. Moreover, the effects were associated with increases in the activities of erα, erß, and cyp19a genes. The respective estrogen receptors (ER) and aromatase (AROM) antagonists significantly attenuated the stimulation of lhß, fshß, LH, and FSH expression, thereby proving that BPA analogs affect the reproductive neuroendocrine system via ERs and AROM pathway. Furthermore, we observed that the reproductive neuroendocrine toxicity of BPAF was more similar to that of BPA. This was the first study to comparatively explore the reproductive neuroendocrine toxicities of bisphenols in aquatic organism.

G protein-coupled estrogen receptor 1 mediates estrogen effect in red common carp (Cyprinus carpio).

G protein-coupled estrogen receptor 1 (GPER1) plays a crucial role in the regulation of non-genomic estrogen effect. However, the research about fish GPER1 is still limited. The present study aims to obtain the full-length sequence of gper1 from red common carp (Cyprinus carpio) and characterize its expression pattern, and to further explore its potential role in regulating the environmental estrogen induced immunotoxicity. We first cloned the full-length mRNA and genomic sequences of gper1 in C. carpio by PCR, and obtained a 1908 bp sequence with a 1062 bp open reading frame encoding GPER1 protein with 353 amino acids. Additionally, qRT-PCR showed that gper1 was expressed across different tissues in C. carpio, with the highest expression in the brain, which is similar to that in zebrafish. Moreover, applying a luciferase reporter system, we found that the promotor sequence of gper1 has strong activity, and similar to GPER1 in other animals, carp GPER1 also has seven-transmembrane domains, indicating its potential functions. We confirmed the binding ability of GPER1 with G1 and G15 in primary macrophages of C. carpio by testing the related gene expression levels after 6 h exposure, and similar to G1, bisphenol A (BPA), a typical environmental estrogen, could interact with GPER1 to increase the Ca2+ concentration in macrophages treated for 30 min. Furthermore, inhibition of GPER1 with GPER1 antagonist G36 rescued the cellular immunotoxicity caused by BPA, which further suggested that carp GPER1 could mediate the estrogen effect. Our findings contribute to better understanding of the role of carp GPER1.

Bioassay guided analysis coupled with non-target chemical screening in polyethylene plastic shopping bag fragments after exposure to simulated gastric juice of Fish.

In this study, fragments of polyethylene plastic bags were treated with simulated gastric juice of fish for 16 h. Following solid-phase extraction, methanol eluents caused acute toxicity to embryos and larvae of Japanese medaka. Chromatographic fractions (polar to more non-polar with numbers increasing) of the extract were evaluated for toxicity and estrogenic activity using medaka and an estrogen receptor (ER) cell-line. Fractions 6 and 9 had the highest estrogenic effects with relative hydrophobic chemicals. The vtg expression in fraction 6 was 22-fold higher than control, and the ER cellular response in fraction 9 was 8.5-fold higher than controls. Following non-target screening (NTS), several novel phthalates and phenols were identified in the above two fractions. Fractions 1 and 2 appeared to be primarily responsible for the acute toxicity observed with the whole extract. The hatching rate decreased to 36 % in fraction 2, and was not observed following exposure to fraction 1. NTS of these fractions indicated 635 and 808 entities, respectively, most without toxicity information. These results indicate plastic leachates from gastric juices of fish are complex mixtures of many compounds that can have acute reproductive and sublethal endocrine impacts in fish.

Evidence linking exposure of fish primary macrophages to antibiotics activates the NF-kB pathway.

Low doses of antibiotics are ubiquitous in the marine environment and may exert negative effects on non-target aquatic organisms. Using primary macrophages of common carp, we investigated the mechanisms of action following exposure to several common antibiotics; cefotaxime, enrofloxacin, tetracycline, sulfamonomethoxine, and their mixtures, and explored the immunomodulatory effects associated with the nuclear factor-κB (NF-κB) signaling pathway. A KEGG pathway analysis was conducted using the sixty-six differentially expressed genes found in all treatments, and showed that exposure to 100 µg/L of antibiotics could affect regulation of the NF-κB signaling pathway, suggesting that activation of NF-κB is a common response in all four classes of antibiotics. In addition, the four antibiotics induced nf-κb and NF-κB-associated cytokines expression, as verified by qPCR, however, these induction responses by four antibiotics were minor when compared to the same concentration of LPS treatment (100 µg/L). Antagonists of NF-κB blocked many of the immune effects of the antibiotics, providing evidence that NF-κB pathways mediate the actions of all four antibiotics. Moreover, exposure to environmentally relevant, low levels (0.01-100 µg/L) of antibiotics induced a NF-κB-mediated immune response, including endogenous generation of ROS, activity of antioxidant enzymes, as well as expression of cytokine and apoptosis. Moreover, exposure to mixtures of antibiotics presented greater effects on most tested immunological parameters than exposure to a single antibiotic, suggesting additive effects from multiple antibiotics in the environment. This study demonstrates that exposure of fish primary macrophages to low doses of antibiotics activates the NF-kB pathway.

Early exposure to environmental levels of sulfamethoxazole triggers immune and inflammatory response of healthy zebrafish larvae.

Trace levels of antibiotics are increasingly being detected in aquatic environment and their potential toxicity to aquatic organisms is concerning. Sulfamethoxazole (SMX), a veterinary sulfonamide widely used across the globe, exists ubiquitously in aquatic environment with concentrations up to micrograms per liter. This study aims to investigate the effects of environmentally relevant levels (0.1, 1, 10, 100 µg/L) of SMX on the health of zebrafish during early development. Our results show that SMX delays the hatchment of embryos and reduces the body length. A dose-response relationship of oxidative stress indicators including total-antioxidant capacity (T-AOC), inducible nitric oxide synthase (iNOS) and total nitric oxide synthase (TNOS), catalase (CAT) has been observed. Additionally, SMX up-regulates the gene expression of several key proinflammatory cytokines and their corresponding proteins including interleukin-1ß (IL-1ß), interferon-γ (IFN-γ) and interleukin-11 (IL-11) and the expression of genes including interleukin-6 (il-6), tumor necrosis factor-α (tnf-α). This indicates that early exposure of SMX may evoke inflammation response in healthy fish. Inhibition of lysozyme and recombination-activating genes (rags) suggests that SMX suppresses the ability of zebrafish to resist pathogen. The reduction of the expression of Toll-like receptors (TLRs) related genes and significant correlations between TLRs and other immune-related genes reveal that TLRs might be an immunoregulator of SMX for zebrafish embryos and larvae. The novelty of this study lies in that early exposure to environmental levels of SMX not only affects the growth and development of zebrafish larvae, but also triggers oxidative stress and inflammation, resulting in a reduction in host immune defense via TLRs in healthy fish.

Bisphenol S-induced chronic inflammatory stress in liver via peroxisome proliferator-activated receptor γ using fish in vivo and in vitro models.

Bisphenol S (BPS) has been widely used as a bisphenol alternative in recent few years. However, with mounting evidence suggesting that the presence of BPS in the environment also poses risks to ecosystems and human health, we decided to use the juvenile common carp (Cyprinus carpio) and its primary macrophages as in vivo and in vitro models to examine if BPS is a safe substitute of BPA. The present study evaluated the immune responses of chronic BPS exposure and their mechanisms of action associated with peroxisome proliferator-activated receptor (PPAR) signaling pathway. Potential oxidative stress and pro-inflammatory effects of BPS exposure were identified in fish liver after 60-day exposure, based on the increased reactive oxygen species (ROS) production, antioxidant capacity, NO production, lipid peroxidation, and induction of inflammatory cytokine expression, as well as acute phase protein levels of C-reactive protein, immunoglobulin M, lysozyme, and complement component 3. Moreover, pparγ, PPAR pathway-associated genes retinoid x receptor α (rxrα) and nuclear factor-κb (nfκb) presented a rough concentration-dependent alteration after BPS exposure. An acute BPS exposure to the isolated primary macrophages from juvenile common carp was performed to help elucidate gene expression patterns of pparγ, rxrα, and nfκb in a typical immune cell model, the results were consistent with what we found in vivo experiments for long-term BPS exposure. Furthermore, with coexposure to BPS and a PPARγ antagonist, the restriction of PPAR signaling pathway significantly inhibited the induction of ROS and the mRNA level of interleukin-1ß, confirming the involvement of PPAR pathway in BPS-induced chronic inflammatory stress in liver.

In vivo actions of Bisphenol F on the reproductive neuroendocrine system after long-term exposure in zebrafish.

Although Bisphenol F (BPF), a bisphenol A (BPA) analogue with a similar chemical structure to that of BPA, is widely used in commercial products, little is known about its potential toxic effects on the reproductive neuroendocrine system in vivo. The present study aimed to comprehensively evaluate the effects of BPF on the reproductive neuroendocrine system in zebrafish and to assess the potential mechanisms underlying its association with estrogen receptor (ER) and aromatase (AROM) pathways. Long-term exposure to environmentally relevant and low levels of BPF led to increased expression of reproductive neuroendocrine-related genes (kiss1, kiss1r, gnrh3, lhß, and fshß) in the zebrafish brain, as well as increased levels of adrenocorticotropic, gonadotropin-releasing, luteinizing, and follicle-stimulating hormones in the zebrafish brain and vitellogenin in the zebrafish liver. In addition, these effects were associated with an increase in erα, erß, cyp19a, and cyp19b activity. Meanwhile, ER and AROM antagonists, alone or in combination, significantly attenuated the stimulation of kiss1, lhß, vtg, and gnrh3 expression, thereby suggesting that chronic BPF exposure affects the regulation of the reproductive neuroendocrine system through activation of the ER and AROM pathways. Moreover, since BPF and bisphenol S induced toxic and reproductive neuroendocrine effects similar to those of BPA, the current accepted usage of BPA and its analogs should be reconsidered in the future.

The occurrence, potential toxicity, and toxicity mechanism of bisphenol S, a substitute of bisphenol A: A critical review of recent progress.

Bisphenol S (BPS) has been introduced into the industry as a safer alternative to bisphenol A (BPA). The distribution of BPS has recently become an important issue worldwide, but investigations on the toxicity and mechanisms of BPS remain limited. A review of the literature reveals that BPS has widespread presence in environmental media, such as indoor dust, surface water, sediments, and sewage sludge. It has been detected in plants, paper products, some food items, and even in the human body. In addition, compared to BPA, BPS has a lower acute toxicity, similar or less endocrine disruption, similar neurotoxicity and immunotoxicity, and lower reproductive and developmental toxicity. The mechanisms underlying BPS toxicity may be related to the chemical properties of BPS in the human body, including interactions with estrogen receptors, and binding to DNA and some proteins, subsequently including exerting oxidative stress. However, further investigation on the potential risks of BPS to humans and its mechanisms of toxicity should be conducted to better understand and control the risks of such novel chemicals.

Genome-wide identification of the interactions between key genes and pathways provide new insights into the toxicity of bisphenol F and S during early development in zebrafish.

Bisphenol F (BPF) and bisphenol S (BPS) have been widely used as alternatives to bisphenol A (BPA). With their increasing use, BPF and BPS have also been released into the environment; thus, their potential risks to aquatic organisms and humans are drawing attention. The objective of this study was to identify the interactions between key pathways and hub genes in zebrafish following BPF and BPS exposure, and to evaluate the potential risks to human health. We identified three key pathways using KEGG over-representation test and Gene Set Enrichment Analysis (GSEA): 'Necroptosis,' 'Adipocytokine signaling pathway,' and 'C-type lectin receptor signaling pathway.' Moreover, three hub genes (mst1ra, prkcdb, and pik3cb) and detailed interactions among the pathways were examined by the analyses of PPI network, subcellular location, and shortest-pathway. Surprisingly, all three pathways were strongly associated with a potential risk of cancer, as reported previously. In addition, the results of KOBAS shown in 'Pathways in Cancer' and 'Cancers' belong to the top 10 terms in pathway enrichment analyses using genes related to BPF or BPS in human, as was found using GenCLiP. Moreover, the Kaplan-Meier survival analysis was performed using homologenes (MST1R, PIK3CB and PRKCD) of hub genes in human to evaluate whether exposure to bisphenols may adversely affect breast cancer. Taken together, these studies demonstrate the potential carcinogenicity of BPF and BPS. To our knowledge, this is the first study on three overlapping key pathways and three hub genes to investigate BPF and BPS exposure-related mechanisms and subsequent interactions in zebrafish.

Tacrolimus decreases proteinuria in patients with refractory IgA nephropathy.

In clinical practice, some IgA nephropathy (IgAN) patients show resistance to or are unable to achieve complete remission using steroids and/or immunosuppressants. The current study aimed to assess the efficacy and safety of tacrolimus in the treatment of cases of refractory IgAN.In this retrospective observational study, 34 primary IgAN patients with refractory proteinuria received tacrolimus for at least 12 months. Complete remission, partial remission, and other clinical data were measured at 1, 3, 6, and 12 months after the initiation of treatment.After 12 months, complete remission was achieved in 20 (58.8%) patients and partial remission in 5 (14.7%) patients, yielding a total response rate of 73.5%. The mean time for response to tacrolimus for those who achieved complete remission and partial remission was 7.0 ±â€Š4.7 weeks. Serum creatinine (Scr), uric acid, estimated glomerular filtration rate, alanine aminotransferase, aspartate transaminase, white blood cell count, blood pressure, blood glucose, total cholesterol, and total triglyceride were stable over time. Three patients demonstrated a loss of eGFR >15 mL/min·1.73 m from baseline. Three cases of upper respiratory infection and 2 cases of urinary tract infection were observed during the study. Patients who achieved complete remission had better renal function and lower baseline proteinuria than partial remission and nonresponder patients. Crescent formation in biopsy specimens was seen more often in nonresponder patients.Tacrolimus was safe and effective at lowering proteinuria in refractory IgAN patients. Lower baseline proteinuria and better renal function were associated with a higher probability of complete remission, while crescent formation was associated with a worse prognosis.

Immunotoxicity of bisphenol S and F are similar to that of bisphenol A during zebrafish early development.

Bisphenol S (BPS) and bisphenol F (BPF) have been increasingly used as alternatives to bisphenol A (BPA) owing to health concerns. The present study aims to evaluate the impact of these two BPA analogs on oxidative stress and the immune system during zebrafish embryonic and larval development. Environmentally relevant levels of BPS and BPF exposure could increase reactive oxygen species (ROS) content, nitric oxide (NO) content, nitric oxide synthase (NOS) activity, and the expression of immunity-related genes in concentration dependent manners during the early developmental stages in zebrafish. At a concentration of 100 µg/L, BPS and BPF showed similar effects on the immune toxicity of zebrafish as that of BPA. Moreover, BPS and BPF induced both erα and nf-κb expression, and antagonists of estrogen receptor and NF-κB blocked the effects on immunity-related gene expression, providing evidence that the two pathways mediate the actions of BPS and BPF on fish immune response and functions. Thus we conclude that the presence of BPS and BPF in the environment, similar to BPA, may also pose risks to ecosystem and human health and cannot be widely used without limitations and precautions.

Toxic Effects of Bisphenol S Showing Immunomodulation in Fish Macrophages.

Bisphenol S (BPS), a structural analogue of bisphenol A (BPA), has been increasingly used as a common replacement of BPA due to health concerns regarding the former. However, mounting evidence suggests that BPS has similar endocrine-disrupting effects as BPA, and likewise, its presence in the environment may pose considerable risks to ecosystems and human health. Using fish primary macrophages (fpMQs), we here evaluated the immunomodulatory effects of BPS and its mechanisms of action associated with estrogen receptors (ERs). Following BPS exposure at environmentally relevant concentrations from 0.1 to 1000 µg/L, we observed approximate concentration-dependent increases in nitric oxide and reactive oxygen species generation and total antioxidant capacity as well as the gene expression of inflammatory cytokines in fpMQs. BPS impaired phagocytic capability but enhanced fpMQ activation levels in response to lipopolysaccharide stimulation and promoted apoptosis, indicating an impact on cell functions. At a concentration of 100 µg/L, BPS and BPA showed comparable pro-inflammatory potential with both up-regulating the production of free radicals and cytokine expression; however, BPS had no significant potency with regards to inducing lipid peroxidation and apoptosis, different from BPA's effects. Moreover, BPS induced both erα and erß2 expression in fpMQs, whereas BPA induced only erα expression. This study demonstrates that, similarly to BPA, exposure to low doses of BPS significantly disturbs the immune response of fpMQs in vitro and first reveals overlapping but different roles of ERs in response to BPS and BPA.

Suppressive immunoregulatory effects of three antidepressants via inhibition of the nuclear factor-κB activation assessed using primary macrophages of carp (Cyprinus carpio).

Antidepressants, having been applied for the treatment of major depressive disorder and other conditions for decades, are among the most commonly detected human pharmaceuticals in the aquatic environment. This study evaluated the immunotoxicity of acute exposure to environmentally relevant concentrations of amitriptyline, fluoxetine and mianserin using an in vitro primary macrophage model isolated from red common carp (Cyprinus carpio), and also explored their potential mechanisms of action. A potential suppressive immunoregulatory effect of antidepressant exposure was suggested based on the observed suppressive effects on oxidative stress parameters, bactericidal activity, NO production, and NO synthase activity, as well as pro-inflammatory cytokine gene expression, and a significant stimulatory effect on anti-inflammatory interleukin-10 and interferon cytokine gene expression and ATPase activities in macrophages after 6h-exposure to three individual antidepressants and a combination thereof. Notably, we also found these effects were significantly associated with a corresponding decrease in nuclear factor-κB (NF-κB) activity after antidepressants exposure, and the NF-κB antagonist significantly restrained the effects of antidepressants on gene expression of cytokines, indicating that antidepressants could alter the response of various immune-associated components via the inhibition of NF-κB. Moreover, time-dependent lethal concentrations of three antidepressants on primary macrophages were firstly determined at mg/L levels, and the synergetic effects of antidepressant mixtures were suggested and in particular, for some parameters including total antioxidant capacity and cytokine genes expression, they could be significantly affected by antidepressants exposure at concentrations as low as 10ng/L, which together thereby revealed the potential risk of antidepressants to aquatic life.

Decreased DACH1 expression in glomerulopathy is associated with disease progression and severity.

Cell fate determination factor dachshund1 (DACH1) is a chromosome-associated protein that regulates cellular differentiation throughout development. Recent genome-wide association studies have show that missense mutation in DACH1 leads to hereditary renal hypodysplasia. Renal DACH1 expression can be used to estimate glomerular filtration rate (eGFR). We firstly characterized the function of DACH1 in normal and diseased renal tissue using immunohistochemistry to assess DACH1 in human renal biopsy specimens from 40 immunoglobulin A nephropathy (IgAN) patients, 20 idiopathic membranous nephropathy (IMN) patients, and 15 minimal change disease (MCD) patients. We found that DACH1 expression was decreased in the nephropathy group relative to healthy controls. DACH1 staining in the glomerulus correlated positively with eGFR (r = 0.41, p < 0.001) but negatively with serum creatinine (r = -0.37, p < 0.01). In vitro, DACH1 overexpression in human podocytes or HK2 cells decreased expression of cyclin D1, but increased expression of p21 and p53, which suggested that DACH1 overexpression in human podocytes or HK2 cells increased the G1/S phase or G2/M cell arrest. Together, These findings indicate that DACH1 expression is decreased in glomerulopathy imply a potential role for DACH1 in the this development of human chornic glomerulopathy. These data suggest that DACH1 is a potential a marker of disease progression and severity for glomerular diseases.

Absorption fever characteristics due to percutaneous renal biopsy-related hematoma.

This study aims to describe the unique characteristics of absorption fever in patients with a hematoma after percutaneous renal biopsy (PRB) and distinguish it from secondary infection of hematoma.We retrospectively studied 2639 percutaneous renal biopsies of native kidneys. We compared the clinical characteristics between 2 groups: complication group (gross hematuria and/or perirenal hematoma) and no complication group. The axillary temperature of patients with a hematoma who presented with fever was measured at 06:00, 10:00, 14:00, and 18:00. The onset and duration of fever and the highest body temperature were recorded. Thereafter, we described the time distribution of absorption fever and obtained the curve of fever pattern.Of 2639 patients, PRB complications were observed in 154 (5.8%) patients. Perirenal hematoma was the most common complication, which occurred in 118 (4.5%) of biopsies, including 74 small hematoma cases (thickness ≤3 cm) and 44 large hematoma cases (thickness >3 cm). Major complications were observed in only 6 (0.2%) cases resulting from a large hematoma. Of 118 patients with a perirenal hematoma, absorption fever was observed in 48 cases. Furthermore, large hematomas had a 5.23-fold higher risk for absorption fever than the small ones.Blood pressure, renal insufficiency, and prothrombin time could be risk factors for complications. Fever is common in patients with hematoma because of renal biopsy and is usually noninfectious. Evaluation of patients with post-biopsy fever is necessary to identify any obvious infection sources. If no focus is identified, empiric antibiotic therapy should not be initiated nor should prophylactic antibiotics be extended for prolonged durations. Absorption fevers will resolve in time without specific therapeutic interventions.

The potential immune modulatory effect of chronic bisphenol A exposure on gene regulation in male medaka (Oryzias latipes) liver.

Bisphenol A (BPA) is a well-known estrogenic endocrine disrupting chemical (EDC) ubiquitously present in various environmental media. The present study aims to identify the responsive genes in male fish chronically exposed to low concentrations of BPA at the transcription level. We screened genes from a suppression subtractive hybridization library constructed from male medaka (Oryzias latipes) livers after 60-d exposure to 10µg/L BPA under the condition at which changes of hepatic antioxidant parameters have been previously reported. The identified genes were predicted to be involved in multiple biological processes including antioxidant physiology, endocrine system, detoxification, notably associated with the immune response processes. With real time PCR analysis, the immune-associated genes including hepcidin-like precursor, complement component and factors, MHC class I, alpha-2-macroglobulin and novel immune-type receptor 6 isoform were significantly up-regulated in a nonmonotonic dose response pattern in livers upon exposure to different concentrations of BPA (0.1, 1, 10, 100, 1000µg/L). Our results demonstrated a negative impact on gene regulation in fish chronically exposed to relatively low and environmentally relevant concentrations of BPA, and suggested the potential immune modulatory effect of chronic EDC exposure on fish. The immunotoxicity of BPA and other EDCs should be much concerned for the health of human beings and other vertebrates exposed to it.

The primary culture of carp (Cyprinus carpio) macrophages and the verification of its phagocytosis activity.

This study establishes the primary culture method for red carp (Cyprinus carpio) macrophages in vitro and lays the foundation for further research in the fish immune system. The healthy adult red carp was chosen, and mechanical separation and cell adherent culture methods were used to isolate the primary macrophages. Compared to the traditional method of Percoll discontinuous density gradient isolation, the protocol we reported here makes cell isolation steps more concise and obtains more healthy cells with high macrophage purity. The cells were uniform in size with a clearly visible nucleus. Trypan blue staining and non-radioactive cell proliferation assay were used to detect the cell survival rate. Further, we provide optimum culture conditions which include cell density (1 × 10(7) cells/mL), culture medium (Leibovitz's L-15), pH (7.2-7.4), temperature (26°C), and adherent time (24 h). Macrophages have been identified by nonspecific esterase and Wright-Giemsa staining and have shown to grow very well. In addition, the macrophages have a very strong bactericidal activity against three kinds of bacteria, further verifying good growth conditions and proper function.