Current evidence on the relationships among five polymorphisms in the matrix metalloproteinases genes and prostate cancer risk.

Matrix metalloproteinases (MMPs) had a variety of subtypes, which may be related to tumor invasion and angiogenesis, and the polymorphisms from MMPs have been also associated with the susceptibility to a variety of tumors, including prostate cancer (PCa). However, previous studies have not systematically analyzed the association between MMP and prostate cancer, so we conducted systematic data collection and analyzed to evaluate the relationship among polymorphisms in MMPs and PCa susceptibility. We searched PubMed, Web of Science, Embase and Google Scholar for all papers published up to Apr 3rd, 2023, and systematically analyzed the relationship among MMP1-1607 2G/1G, MMP2-1306 T/C, MMP2-735 T/C, MMP7-181 G/A, MMP9-1562 T/C and PCa susceptibility using multiple comparative models and subgroup analyses. We found that MMP2-1306 T/C polymorphism showed associations with PCa susceptibility, with the Ethnicity subgroup (Asian) being more pronounced. Similarly, MMP9-1562 T/C has also had associations with PCa susceptibility. Our current study found that the polymorphisms of, MMP2-1306 T/C, and MMP9-1562 T/C had strong associations with PCa risk.

Unveiling the hidden pathways: Exploring astrocytes as a key target for depression therapy.

Depressive disorders are widely debilitating psychiatric disease. Despite the considerable progress in the field of depression therapy, extensive research spanning many decades has failed to uncover pathogenic pathways that might aid in the creation of long-acting and rapid-acting antidepressants. Consequently, it is imperative to reconsider existing approaches and explore other targets to improve this area of study. In contemporary times, several scholarly investigations have unveiled that persons who have received a diagnosis of depression, as well as animal models employed to study depression, demonstrate a decrease in both the quantity as well as density of astrocytes, accompanied by alterations in gene expression and morphological attributes. Astrocytes rely on a diverse array of channels and receptors to facilitate their neurotransmitter transmission inside tripartite synapses. This study aimed to investigate the potential processes behind the development of depression, specifically focusing on astrocyte-associated neuroinflammation and the involvement of several molecular components such as connexin 43, potassium channel Kir4.1, aquaporin 4, glutamatergic aspartic acid transporter protein, SLC1A2 or GLT-1, glucocorticoid receptors, 5-hydroxytryptamine receptor 2B, and autophagy, that localized on the surface of astrocytes. The study also explores novel approaches in the treatment of depression, with a focus on astrocytes, offering innovative perspectives on potential antidepressant medications.

Global trends in tumor microenvironment-related research on tumor vaccine: a review and bibliometric analysis.

Background: Tumor vaccines have become crucial in cancer immunotherapy, but, only a limited number of phase III clinical trials have demonstrated clinical efficacy. The crux of this issue is the inability of tumor vaccines to effectively harmonize the tumor microenvironment with its intricate interplay. One factor that can hinder the effectiveness of vaccines is the natural immunosuppressive element present in the tumor microenvironment. This element can lead to low rates of T-cell response specific to antigens and the development of acquired resistance. Conversely, anticancer vaccines alter the tumor microenvironment in conflicting manners, inducing both immune activation and immunological evasion. Hence, comprehending the correlation between tumor vaccines and the tumor microenvironment would establish a foundation for forthcoming tumor treatment. Objective: Our review explores the realm of research pertaining to tumor vaccinations and the tumor microenvironment. Our objective is to investigate the correlation between tumor vaccines and the tumor microenvironment within this domain. We then focus our review on the dominant international paradigms in this research field and visually illustrates the historical progression and emergent patterns observed in the past. Methods: From January 1, 1999 to February 7, 2023, 1420 articles on the interplay between tumor vaccines and the tumor microenvironment were published, according to The Clarivate Web of Science (WOS) database used in our review. A bibliometric review was designed for this collection and consisted of an evaluation. The evaluation encompassed various discernible attributes, including the year of publication, the journals in which the articles were published, the authors involved, the affiliated institutions, the geographical locations of the institutions, the references cited, and the keywords employed. Results: Between the years 1999 and 2022, publications saw a significant increase, from 3 to 265 annually. With 72 papers published, Frontiers in Immunology had the most manuscripts published. The Cancer Research publication garnered the highest number of citations, amounting to 2874 citations. The United States exerts significant dominance in the subject, with the National Cancer Institute being recognized as a prominent institution in terms of both productivity and influence. Furthermore, Elizabeth M. Jaffee was recognized as the field's most prolific and influential author with 24 publications and 1,756 citations. The co-occurrence cluster analysis was conducted on the top 197 keywords, resulting in the identification of five distinct clusters. The most recent high-frequency keywords, namely immune therapy, dendritic cell, tumor microenvironment, cancer, and vaccine, signify the emerging frontiers in the interaction between tumor vaccines and the tumor microenvironment. Conclusion: Our review uncovers insights into contemporary trends, global patterns of collaboration, fundamental knowledge, research areas of high interest, and emerging frontiers in the field of TME-targeted vaccines.

Neurological and metabolic related pathophysiologies and treatment of comorbid diabetes with depression.

BACKGROUND: The comorbidity between diabetes mellitus and depression was revealed, and diabetes mellitus increased the prevalence of depressive disorder, which ranked 13th in the leading causes of disability-adjusted life-years. Insulin resistance, which is common in diabetes mellitus, has increased the risk of depressive symptoms in both humans and animals. However, the mechanisms behind the comorbidity are multi-factorial and complicated. There is still no causal chain to explain the comorbidity exactly. Moreover, Selective serotonin reuptake inhibitors, insulin and metformin, which are recommended for treating diabetes mellitus-induced depression, were found to be a risk factor in some complications of diabetes. AIMS: Given these problems, many researchers made remarkable efforts to analyze diabetes complicating depression from different aspects, including insulin resistance, stress and Hypothalamic-Pituitary-Adrenal axis, neurological system, oxidative stress, and inflammation. Drug therapy, such as Hydrogen Sulfide, Cannabidiol, Ascorbic Acid and Hesperidin, are conducive to alleviating diabetes mellitus and depression. Here, we reviewed the exact pathophysiology underlying the comorbidity between depressive disorder and diabetes mellitus and drug therapy. METHODS: The review refers to the available literature in PubMed and Web of Science, searching critical terms related to diabetes mellitus, depression and drug therapy. RESULTS: In this review, we found that brain structure and function, neurogenesis, brain-derived neurotrophic factor and glucose and lipid metabolism were involved in the pathophysiology of the comorbidity. Obesity might lead to diabetes mellitus and depression through reduced adiponectin and increased leptin and resistin. In addition, drug therapy displayed in this review could expand the region of potential therapy. CONCLUSIONS: The review summarizes the mechanisms underlying the comorbidity. It also overviews drug therapy with anti-diabetic and anti-depressant effects.

Global trends in COVID-19 Alzheimer's related research: a bibliometric analysis.

Background: The COVID-19 pandemic has significantly impacted public health, putting people with Alzheimer's disease at significant risk. This study used bibliometric analysis method to conduct in-depth research on the relationship between COVID-19 and Alzheimer's disease, as well as to predict its development trends. Methods: The Web of Science Core Collection was searched for relevant literature on Alzheimer's and Coronavirus-19 during 2019-2023. We used a search query string in our advanced search. Using Microsoft Excel 2021 and VOSviewer software, a statistical analysis of primary high-yield authors, research institutions, countries, and journals was performed. Knowledge networks, collaboration maps, hotspots, and regional trends were analyzed using VOSviewer and CiteSpace. Results: During 2020-2023, 866 academic studies were published in international journals. United States, Italy, and the United Kingdom rank top three in the survey; in terms of productivity, the top three schools were Harvard Medical School, the University of Padua, and the University of Oxford; Bonanni, Laura, from Gabriele d'Annunzio University (Italy), Tedeschi, Gioacchino from the University of Campania Luigi Vanvitelli (Italy), Vanacore, Nicola from Natl Ctr Dis Prevent and Health Promot (Italy), Reddy, P. Hemachandra from Texas Tech University (USA), and El Haj, Mohamad from University of Nantes (France) were the authors who published the most articles; The Journal of Alzheimer's Disease is the journals with the most published articles; "COVID-19," "Alzheimer's disease," "neurodegenerative diseases," "cognitive impairment," "neuroinflammation," "quality of life," and "neurological complications" have been the focus of attention in the last 3 years. Conclusion: The disease caused by the COVID-19 virus infection related to Alzheimer's disease has attracted significant attention worldwide. The major hot topics in 2020 were: "Alzheimer' disease," COVID-19," risk factors," care," and "Parkinson's disease." During the 2 years 2021 and 2022, researchers were also interested in "neurodegenerative diseases," "cognitive impairment," and "quality of life," which require further investigation.

The benefits of hesperidin in central nervous system disorders, based on the neuroprotective effect.

Disorders of central nervous system (CNS) disorders are considered serious health issues. The most common CNS diseases include neurodegenerative diseases, mental disorders, demyelinating disease, ischemia-reperfusion injury, and neuroinflammation. As a natural phenolic compound, hesperidin is a flavanone glycoside with various biological effects. Increasing evidence show that the growth of CNS diseases is hindered by hesperidin. Here, we have reviewed the related literature on neuropharmacological mechanisms for the preventive and therapeutic effects of hesperidin on CNS diseases. Several cellular and animal models have been developed to evaluate the underlying neuropharmacological mechanisms of hesperidin. Additionally, clinical evidence has confirmed its neuroprotective function. Hesperidin exerts its neuroprotective properties by decreasing neuro-inflammatory and apoptotic pathways. Hesperidin function has been studied in preclinical models for CNS diseases, but little is known about its definite effect in humans. Hesperidin can effectively alleviate depression and improve cognition and memory. It is urgent to explore and discover clinical trials for further confirmation of the neuroprotective efficacy of hesperidin and to evaluate its safety profile.

Kuijieling decoction suppresses NLRP3-Mediated pyroptosis to alleviate inflammation and experimental colitis in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is an autoimmune disease. Although the mortality rate of UC is not very high, it has a considerable morbidity rate and an unsatisfactory cure rate. Without effective treatment, UC is likely to develop into colon cancer. Kuijieling (KJL) is an effective empirical formula to treat UC in the clinical setting, and it has been proven to have curative effects against UC. AIM OF THE STUDY: In a previous study, we demonstrated that KJL could suppress NOD-like receptor protein 3 (NLRP3) to reduce inflammatory cytokines and alleviate UC. In this study, we investigated the mechanism of KJL in more detail, from the perspective of pyroptosis. MATERIALS AND METHODS: We established a dextran sulfate sodium-induced UC mouse model and RAW264.7 cells to measure different indicators with different experimental methods. The efficiency of KJL was evaluated by measuring the length and unit weight of mouse colons, and assessment of pathological injury was performed using HE staining. We detected different expression levels of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, gasdermin-D C-terminal domain (GSDMD-C), gasdermin-D N-terminal domain (GSDMD-N), IL-1ß, and IL-18 in colon tissues and cells using RT-qPCR and western blotting. Immunohistochemistry was used for tissues and immunofluorescence for cells to confirm protein expression. IL-1ß and IL-18 were measured with enzyme-linked immunosorbent assay in serum, tissue, and cell culture supernatant. MiR-223 was detected using RT-qPCR. RESULTS: After administration of KJL suspension, colon damage in KJL groups was milder than in model groups. ASC, caspase-1, IL-1ß, and IL-18 mRNA levels in colon tissue were decreased to different degrees in the KJL groups. Protein expression of NLRP3, caspase-1, GSDMD-N, IL-1ß, and IL-18 in vivo decreased significantly in the KJL groups. In addition, Mir-223 level decreased in colon tissue of the KJL groups. In vitro, NLRP3, ASC, caspase-1, GSDMD-N, IL-1ß, and IL-18 levels decreased to varying degrees, at both mRNA and protein levels. Mir-223 was lower in the KJL groups than in the model group. Furthermore, KJL was shown to regulate the level of miR-223, which returned to normal after its expression was inhibited or promoted, and the levels of associated indicators also returned to normal after transfection. CONCLUSIONS: KJL is able to inhibit pyroptosis to alleviate UC, but these suppression effects were not mediated through miR-223 regulation.

Kuijieling-Containing Serum Regulates Th17 and Treg Cell Differentiation by Inhibiting STAT3 Signaling In Vitro.

OBJECT: To investigate the effect of Kuijieling (KJL) on the balance between T helper 17 (Th17) and regulatory T (Treg) cells in peripheral blood mononuclear cells (PBMC) in vitro and explore the underlying mechanism. MATERIALS AND METHODS: PBMCs isolated from rats were stimulated with transforming growth factor-ß, interleukin (IL)-6, and IL-23 to induce the imbalance of Th17 and Treg cells and were treated with 10, 5, or 2.5% KJL-containing serum. The proportion of Th17 or Treg cells in CD4+ T cells was analyzed by flow cytometry, the concentrations of IL-17, IL-21, and IL-10 were assayed by ELISA, mRNA expressions of retinoic acid-related orphan receptor γt (RORγt), forkhead box protein 3 (Foxp3), and signal transducer and activator of transcription 3 (STAT3) were quantified by PCR, and phosphorylated STAT3 (p-STAT3) was analyzed by flow cytometry. RESULTS: KJL-containing serum decreased the proportion of Th17 cells and increased the proportion of Treg cells in CD4+ T cells, decreased the concentration of IL-17 and IL-21, enhanced the level of IL-10 in the cell culture supernatant, promoted the expression of Foxp3, and inhibited the levels of RORγt, STAT3, and p-STAT3. CONCLUSION: KJL suppresses the STAT3 pathway to remedy the imbalance between Th17 and Treg cells.

Kuijieling regulates the differentiation of Treg and Th17 cells to ameliorate experimental colitis in rats.

BACKGROUND: Regulatory T (Treg) cells and T helper 17 (Th17) cells play crucial roles in ulcerative colitis (UC). Kuijieling (KJL) is an effective Chinese medicine formula for treating UC in clinic. Kuijieling has shown remedy effect on the imbalance between Treg and Th17 cells. This study aimed to further reveal the exact underlying mechanism of how Kuijieling regulates the differentiation of Treg and Th17 cells in the treatment of UC. METHODS: Colitis was induced by trinitrobenzene sulfonic acid in rats and treated by KJL. Pathological injury was evaluated by HE staining and pathological score. Transforming growth factor-ß1 (TGF-ß1), interleukin(IL)-2, IL-6, IL-10, IL-17, IL-23 and IL-21 in plasma were assayed by ELISA. Forkhead box P3 (Foxp3), signal transducer and activator of transcription (STAT) 5 expressed in colon mucosa were measured by western blot. Immunohistochemistry was employed for quantifying retinoic acid-related orphan receptor γt (RORγt) and STAT3 in colon. RT-PCR was used to analyze the expression of IL-2, IL-17, IL-23, IL-21 mRNA in colon. RESULTS: After the administration of KJL, pathological injury in colon mucosa was reduced and histological score was decreased, transforming growth factor-ß1 (TGF-ß1), interleukin(IL)-2, IL-10 in blood and Foxp3, STAT5, IL-2 in colon increased significantly, IL-6, IL-23, IL-17, IL-21 in blood and RORγt, STAT3, IL-23, IL-17, IL-21 in colon decreased. Our result showed that KJL regulates the related cytokines and transcription factors to promote Treg cells and suppress Th17 cells. CONCLUSION: KJL restores the balance between Treg and Th17 cells through regulating the differentiation of them, therefore contributes to the treatment of UC.

The Impact of Impoundment on Mercury Bioaccumulation in Fish Downstream from a Newly Constructed Reservoir, Wujiang River, Southwest China.

Mercury concentrations in fish were investigated downstream from a newly impounded subtropical reservoir in August 2008. After 6-7 months of reservoir impoundment, mean mercury concentration in fish from downstream is significantly increased by 1.9 times. Not only carnivorous fish but also benthic fish had significantly higher total mercury concentrations than others. No significant correlation was found between total mercury concentrations and body length or weight of 13 fish species. Compared with the pre-impoundment, total mercury in fish from downstream is significantly increased by reservoir impoundment, but the increased rate is lower than those in subarctic and temperate areas. Fish samples surpassed the Chinese hygienic standard for tolerances of mercury in foods increased by 4.3%. More attention should be given to fish mercury levels from downstream sites to prevent possible adverse effects on the health of local people.

Acute toxicity, respiratory reaction, and sensitivity of three cyprinid fish species caused by exposure to four heavy metals.

Using 3 cyprinid fish species zebra fish, rare minnow, and juvenile grass carp, we conducted assays of lethal reaction and ventilatory response to analyze sensitivity of the fish to 4 heavy metals. Our results showed that the 96 h LC50 of Hg(2+) to zebra fish, juvenile grass carp, and rare minnow were 0.14 mg L(-1), 0.23 mg L(-1), and 0.10 mg L(-1), respectively; of Cu(2+)0.17 mg L(-1), 0.09 mg L(-1), and 0.12 mg L(-1) respectively; of Cd(2+)6.5 mg L(-1), 18.47 mg L(-1), 5.36 mg L(-1), respectively; and of Zn(2+)44.48 mg L(-1), 31.37 mg L(-1), and 12.74 mg L(-1), respectively. Under a 1-h exposure, the ventilatory response to the different heavy metals varied. Ventilatory frequency (Vf) and amplitude (Va) increased in zebra fish, juvenile grass carp, and rare minnows exposed to Hg(2+) and Cu(2+) (P<0.05), and the Vf and Va of the 3 species rose initially and then declined when exposed to Cd(2+). Zn(2+) had markedly different toxic effects than the other heavy metals, whose Vf and Va gradually decreased with increasing exposure concentration (P<0.05). The rare minnow was the most highly susceptible of the 3 fish species to the heavy metals, with threshold effect concentrations (TEC) of 0.019 mg L(-1), 0.046 mg L(-1), 2.142 mg L(-1), and 0.633 mg L(-1) for Hg(2+), Cu(2+), Cd(2+), and Zn(2+), respectively. Therefore, it is feasible to use ventilatory parameters as a biomarker for evaluating the pollution toxicity of metals and to recognize early warning signs by using rare minnows as a sensor.

Short-term impact of reservoir impoundment on the patterns of mercury distribution in a subtropical aquatic ecosystem, Wujiang River, southwest China.

Surveys on pre- and post-impoundment total mercury concentrations in water, seston and fish were conducted during 2007-2008 in the Wujiang River, southwest China. Compared with the pre-impoundment, total mercury in the reservoir and downstream water rapidly increased by 164-303 % during the first half year of flooding, and then decreased by 61.7-62.2 % after 9 months of flooding. However, total mercury in seston from the reservoir and downstream generally declined. There was no significant difference in the total mercury between reservoir fish with different habitat preference and feeding habit. We find that fish tissue mercury concentration significantly increased threefold after flooding, and the increasing rate is lower than those in subarctic and temperate reservoirs. The pre- and post-impoundment fish samples exceeding the Chinese hygienic standard for tolerances of mercury in foods increased from 1.3 to 17.4 %. Long-term monitoring of fish mercury level in Wujiang River should be undertaken to ensure local food security.

Spatiotemporal distributions of nutrients in the downstream from Gezhouba Dam in Yangtze River, China.

INTRODUCTION: From December 2008 to November 2009, an investigation of water quality was performed in the 70-km long downstream from Gezhouba Dam in Yangtze River. METHODS: Twelve sites in all were chosen. Nine parameters of water quality including the total phosphorus, the total nitrogen, chlorophyll a (Chl.a), nitrite, nitrate, ammonia, water temperature, DO, and pH were monitored almost monthly. The multivariate statistical technique (cluster analysis) and the nonparametric method (Kruskal-Wallis Test and Spearman's rank correlation) were applied to evaluate the spatiotemporal variations of water quality data sets. RESULTS AND DISCUSSION: According to the Chinese environmental quality standards for surface water (GB3838-2002), the water quality in the river section investigated can attain to the III water standards except total nitrogen. Further analysis indicated that there were no significant spatial differences in these parameters of water quality, but the sampling date had a significant effect. The temporal variation of water quality can be related to the discharge of Gezhouba Dam and moreover be affected by the reservoir regulation. During the discharge, the discharge increased the concentration of total phosphorus and then decreased the N:P ratio, which helps to the occurrence of algae blooms. The high consternation of phosphorus and the low N:P ratio show that the water body can be in the process of eutrophication during the discharge of Gezhouba Dam. In fact, Chl.a had begun to rise in the same period.

Feeding habits and habitats preferences affecting mercury bioaccumulation in 37 subtropical fish species from Wujiang River, China.

The present study is the first to report the total mercury concentration of 37 fish species collected from Wujiang River, which is the largest branch on the southern bank of Yangtze River, China and proposed for hydropower development. Total mercury concentrations varied among the 37 subtropical species examined. We found higher mercury concentrations in carnivorous species demonstrating greater mercury bioaccumulation in species with more predatory feeding habits. There is no significant difference between fish grouped by habitat preference and feeding habit. However, carnivorous species preferring benthic positions had higher total mercury concentrations than others suggesting that mercury accumulation is related to the interaction of feeding habit and habitat preference. In our study, fish that are bottom living and feed on other fish or aquatic animals are more likely at high risk of mercury exposure. Additional mercury contamination and future impoundment may raise mercury concentration in fish in the Wujiang causing concern for human health and ecological impacts.

Present status and changes of the phytoplankton community after invasion of Neosalanx taihuensis since 1982 in a deep oligotrophic plateau lake, Lake Fuxian in the subtropical China.

Phytoplankton assemblages in the subtrophical oligotrophic Lake Fuxian, the second deepest lake in China, were investigated monthly from September 2002 to August 2003. A total of 113 species belonging to seven phyla were identified, among them, a filamentous green alga, Mougeotia sp., dominated almost throughout the study period and comprised most of the total phytoplankton biomass. Mougeotia sp. has made a substantial development during the past decades: it was absent in 1957, only occasionally present in 1983, increased substantially in 1993, and became predominant in 2002-2003. It is likely that natural invasion of the Taihu Lake noodlefish (Neosalanx taihuensis) has led to a change of dominant herbivorous zooplankton from small to large calanoid, which has increased grazing pressure on small edible algae, and thus has indirectly favored the development of the inedible filamentous Mougeotia sp.

The low TN:TP ratio, a cause or a result of Microcystis blooms?

An enclosure experiment in the shallow, subtropical Lake Donghu, China, was performed in the summer of 2001 to examine the effect of TN:TP (total phosphorus) ratios and P-reduction on the occurrence of Microcysitis blooms. The treatments were performed with enough amounts of N but with different amounts of P in the water column and sediment. Microcystis blooms occurred in the enclosures either with an initial TN:TP <29 or TN:TP>29 where the nutrients (N, P) were high enough. Microcysitis blooms never occurred in the treatments with low P concentration in spite of the presence of sufficient N. The P-rich sediments served as an important source for the P supply in the water column, and such a process was activated greatly by the outburst of Microcystis blooms which pumped up selectively P from the sediments and thus decreased the TN:TP ratios. Therefore, the low TN:TP ratio is not a cause but rather a result of Microcystis blooms.