•We make an analysis on the seasonal variability of water quality in the Wei River basin.•Land use type in the dry season has a more significant correlation than in the rainy season on both the water ...quantity and quality.•Steeper lands generally have a stronger influence on the stream water quality than flatter lands.•Seasonal variability also occurs in the relationship between topographic characteristics and water quality.•The same land use type plays different, positive or negative, roles on stream water quality in different land use patterns.
The effect of topographic characteristics of land uses on stream water quality must be addressed for a better understanding of the complex relationship between land use and stream water quality. In this study, Geographic Information System (GIS) and Pearson correlation analysis were used to determine whether there were relationship between land use types and stream water quality at the sub-basin scale in the Wei River basin, China, during the dry and rainy seasons in 2012. Temporal variation of these relations was observed, indicating that the relationships between water quality variables and different land uses were weaker in rainy seasons than that in dry seasons. Compared with other land uses, agriculture and urban lands had a stronger relationship with water quality variables in both rainy and dry seasons. Topographic characteristics of land use were employed to further analyze these relationships. The results showed that seasonal variation also occurred in the complex relationship, and land uses in steeper slopes generally had a stronger influence on stream water quality than those in flatter ones. For the riparian zone of each sampling site, the slope coefficients were weaker than those at the sub-basin scale. Land use type near stream water was generally a better indicator for the effectiveness of water quality. These results suggest that the slope and proximity should be taken into account for better land use management.
Nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) are intracellular proteins with a central role in innate and adaptive immunity. As a member of pattern recognition receptors ...(PRRs), NLRs sense specific pathogen-associated molecular patterns, trigger numerous signaling pathways and lead to the secretion of various cytokines. In recent years, cumulative studies have revealed the significant impacts of NLRs in gastrointestinal (GI) inflammatory diseases and cancers. Deciphering the role and molecular mechanism of the NLR signaling pathways may provide new opportunities for the development of therapeutic strategies related to GI inflammatory diseases and GI cancers. This review presents the structures and signaling pathways of NLRs, summarizes the recent advances regarding NLR signaling in GI inflammatory diseases and GI cancers and describes comprehensive therapeutic strategies based on this signaling pathway.
Long-term diabetes-associated complications are the major causes of morbidity and mortality in individuals with diabetes. These diabetic complications are closely linked to immune system activation ...along with chronic, non-resolving inflammation, but therapies to directly reverse these complications are still not available. Our previous study demonstrated that mesenchymal stem cells (MSCs) attenuated chronic inflammation in type 2 diabetes mellitus (T2DM), resulting in improved insulin sensitivity and islet function. Therefore, we speculated that MSCs might exert anti-inflammatory effects and promote the reversal of diabetes-induced kidney, liver, lung, heart, and lens diseases in T2DM rats.
We induced a long-term T2DM complication rat model by using a combination of a low dose of streptozotocin (STZ) with a high-fat diet (HFD) for 32 weeks. Adipose-derived mesenchymal stem cells (ADSCs) were systemically administered once a week for 24 weeks. Then, we investigated the role of ADSCs in modulating the progress of long-term diabetic complications.
Multiple infusions of ADSCs attenuated chronic kidney disease (CKD), nonalcoholic steatohepatitis (NASH), lung fibrosis, and cataracts; improved cardiac function; and lowered serum lipid levels in T2DM rats. Moreover, the levels of inflammatory cytokines in the serum of each animal group revealed that ADSC infusions were able to not only inhibit pro-inflammatory cytokines IL-6, IL-1β, and TNF-α expression but also increase anti-inflammatory cytokine IL-10 systematically. Additionally, MSCs reduced the number of iNOS(+) M1 macrophages and restored the number of CD163(+) M2 macrophages.
Multiple intravenous infusions of ADSCs produced significant protective effects against long-term T2DM complications by alleviating inflammation and promoting tissue repair. The present study suggests ADSCs may be a novel, alternative cell therapy for long-term diabetic complications.
Cyanobacteria blooms in aquaculture ponds harm the harvesting of aquatic animals and threaten human health. Therefore, it is crucial to identify key drivers and develop methods to predict ...cyanobacteria blooms in aquaculture water management. In this study, we analyzed monitoring data from 331 aquaculture ponds in central China and developed two machine learning models - the least absolute shrinkage and selection operator (LASSO) regression model and the random forest (RF) model - to predict cyanobacterial abundance by identifying the key drivers. Simulation results demonstrated that both machine learning models are feasible for predicting cyanobacterial abundance in aquaculture ponds. The LASSO model (R2 = 0.918, MSE = 0.354) outperformed the RF model (R2 = 0.798, MSE = 0.875) in predicting cyanobacteria abundance. Farmers with well-equipped aquaculture ponds that have abundant water monitoring data can use the nine environmental variables identified by the LASSO model as an operational solution to accurately predict cyanobacteria abundance. For crude ponds with limited monitoring data, the three environmental variables identified by the RF model provide a convenient solution for useful cyanobacteria prediction. Our findings revealed that chemical oxygen demand (COD) and total organic carbon (TOC) were the two most important predictors in both models, indicating that organic carbon concentration had a close relationship with cyanobacteria growth and should be considered a key metric in water monitoring and pond management of these aquaculture ponds. We suggest that monitoring of organic carbon coupled with phosphorus reduction in feed usage can be an effective management approach for cyanobacteria prevention and to maintain a healthy ecological state in aquaculture ponds.
•Two machine learning models were developed for cyanobacteria abundance predicting.•Organic carbon concentration was identified as a key metric for cyanobacteria bloom.•The LASSO model was provided which can precisely predict cyanobacteria abundance.•Organic carbon monitoring coupled with phosphorus reduction in feed were suggested.
Nonalcoholic fatty liver disease (NAFLD) is increasingly common among patients with type 2 diabetes mellitus (T2DM). The two conditions can act synergistically to produce adverse outcomes. However, ...the therapeutic options for patients with NAFLD and T2DM are currently limited. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) have shown therapeutic potential for diabetes and hepatic disorders such as liver cirrhosis and fulminant hepatic failure. The present study is aimed at investigating the effect of human UC-MSCs on a mouse model of NAFLD and T2DM, characterized by obesity-induced hyperglycaemia, dyslipidaemia, hepatic steatosis, and liver dysfunction. Thirty-week-old male C57BL/6 db/db mice were infused with human UC-MSCs or phosphate-buffered saline (PBS) via the tail vein once a week for six weeks. Age-matched male C57BL/6 wild-type db/+ mice were used as controls. Body weight and random blood glucose were measured every week. One week after the sixth infusion, intraperitoneal glucose tolerance tests and insulin tolerance tests were performed and the blood and liver were harvested for biochemical and histopathological examinations. Quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR), immunofluorescence staining, and western blot were performed to monitor the expression of the lipid metabolism- and regulatory pathway-related genes. UC-MSC infusions significantly ameliorated hyperglycaemia, attenuated the elevation of hepatic transaminases, and decreased lipid contents, including triglyceride, total cholesterol, and low-density lipoprotein cholesterol. Moreover, histological lesions in the liver diminished markedly, as evidenced by reduced lipid accumulation and attenuated hepatic steatosis. Mechanistically, UC-MSCs were found to regulate lipid metabolism by increasing the expression of fatty acid oxidation-related genes and inhibiting the expression of lipogenesis-related genes, which were associated with the upregulation of the HNF4α-CES2 pathway. Our results demonstrate that human UC-MSCs can ameliorate NAFLD and reverse metabolic syndrome in db/db mice. Thus, UC-MSCs may serve as a novel therapeutic agent for T2DM patients with NAFLD.
ABSTRACT
Aims/Introduction
The Metabolic Score for Insulin Resistance (METS‐IR) is a novel non‐insulin‐based metabolic index used as a substitution marker of insulin resistance. However, whether ...METS‐IR is associated with the urinary albumin‐to‐creatinine ratio (UACR) is not well known. Therefore, we explored the associations between METS‐IR and UACR, and compared the discriminative ability of METS‐IR and its components for elevated UACR.
Materials and Methods
This study included 37,290 participants. METS‐IR was calculated as follows: (Ln2 × fasting blood glucose + fasting triglyceride level × body mass index) / (Ln high‐density lipoprotein cholesterol). Participants were divided into four groups on the basis of METS‐IR: <25%, 25–49%, 50–74% and ≥75%. Logistic regression analyses were carried out to determine the associations between METS‐IR versus its components (fasting blood glucose, triglyceride level, body mass index and high‐density lipoprotein cholesterol) with UACR.
Results
Participants with the highest quartile METS‐IR presented a more significant trend toward elevated UACR than toward its components (odds ratio 1.260, 95% confidence interval 1.152–1.378, P < 0.001 in all participants; odds ratio 1.321, 95% confidence interval 1.104–1.579, P = 0.002 in men; odds ratio 1.201, 95% confidence interval 1.083–1.330, P < 0.001 in women). There were significant associations between METS‐IR and UACR in younger participants (aged <65 years for women and aged 55–64 years for men). Increased METS‐IR was significantly associated with UACR in men with fasting blood glucose ≥5.6 or postprandial blood glucose ≥7.8 mmol/L and systolic blood pressure ≥120 or diastolic blood pressure ≥80 mmHg. The relationships were significant in women with diabetes and hypertension.
Conclusions
Increased METS‐IR was significantly associated with elevated UACR, its discriminative power for elevated UACR was superior to that of its components.
Objectives: To explore the therapeutic effects of M2 macrophages in diabetic nephropathy (DN) and their mechanism.Methods: We infused M2 macrophages stimulated with IL-4 into 10-week-old db/db mice ...once a week for 4 weeks through the tail vein as M2 group. Then we investigated the role of M2 macrophages in alleviating the infammation of DN and explored the mechanism.Results: M2 macrophages hindered the progression of DN, reduced the levels of IL-1β (DN group was 34%, M2 group was 13%, p < 0.01) and MCP-1 (DN group was 49%, M2 group was 16%, p < 0.01) in the glomeruli. It was also proven that M2 macrophages alleviate mesangial cell injury caused by a high glucose environment. M2 macrophage tracking showed that the infused M2 macrophages migrated to the kidney, and the number of M2 macrophages in the kidney reached a maximum on day 3. Moreover, the ratio of M2 to M1 macrophages was 2.3 in the M2 infusion group, while 0.4 in the DN group (p < 0.01). Mechanistically, M2 macrophages downregulated Janus kinase (JAK) 2 and signal transducer and activator of transcription (STAT) 3 in mesangial cells.Conclusions: Multiple infusions of M2 macrophages significantly alleviated inflammation in the kidney and hindered the progression of DN at least partially by abrogating the M1/M2 homeostasis disturbances and suppressing the JAK2/STAT3 pathway in glomerular mesangial cells. M2 macrophage infusion may be a new therapeutic strategy for DN treatment.Objectives: To explore the therapeutic effects of M2 macrophages in diabetic nephropathy (DN) and their mechanism.Methods: We infused M2 macrophages stimulated with IL-4 into 10-week-old db/db mice once a week for 4 weeks through the tail vein as M2 group. Then we investigated the role of M2 macrophages in alleviating the infammation of DN and explored the mechanism.Results: M2 macrophages hindered the progression of DN, reduced the levels of IL-1β (DN group was 34%, M2 group was 13%, p < 0.01) and MCP-1 (DN group was 49%, M2 group was 16%, p < 0.01) in the glomeruli. It was also proven that M2 macrophages alleviate mesangial cell injury caused by a high glucose environment. M2 macrophage tracking showed that the infused M2 macrophages migrated to the kidney, and the number of M2 macrophages in the kidney reached a maximum on day 3. Moreover, the ratio of M2 to M1 macrophages was 2.3 in the M2 infusion group, while 0.4 in the DN group (p < 0.01). Mechanistically, M2 macrophages downregulated Janus kinase (JAK) 2 and signal transducer and activator of transcription (STAT) 3 in mesangial cells.Conclusions: Multiple infusions of M2 macrophages significantly alleviated inflammation in the kidney and hindered the progression of DN at least partially by abrogating the M1/M2 homeostasis disturbances and suppressing the JAK2/STAT3 pathway in glomerular mesangial cells. M2 macrophage infusion may be a new therapeutic strategy for DN treatment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background Mesenchymal stem cells (MSCs) exert anti-diabetic effects and improve long-term complications via secretory effects that regulate macrophage polarisation and attenuate inflammation. ...Enhancing the efficacy of MSCs needs to be explored further. The in vitro culture microenvironment influences the secretory profile of MSCs. Therefore, we hypothesised that a diabetic microenvironment would promote the secretion of cytokines responsible for macrophage polarisation, further attenuating systemic inflammation and enhancing the effects of MSCs on type 2 diabetes (T2D) and long-term diabetic complications. Methods Preconditioned adipose-derived mesenchymal stem cells (pre-ADSCs) were obtained after co-cultivating ADSCs in a diabetic metabolic environment (including high sugar, advanced glycation end-product, and lipopolysaccharides). The regulatory effects of pre-ADSCs on macrophages were observed in vitro. A T2D rat model was induced with a high-fat diet for 32 weeks combined with an intraperitoneal injection of streptozotocin. Sprague-Dawley (SD) rats were divided into four groups: normal group, diabetes without treatment group (PBS), ADSC treatment group, and pre-ADSC treatment group. ADSCs and pre-ADSCs were intravenously administered weekly to SD rats for 6 months, and then glucose homeostasis and long-term diabetic complications were evaluated in each group. Results The secretion of cytokines related to M2 macrophage polarisation (IL-6, MCP-1, etc.) was increased in the pre-ADSC group in the in vitro model. Pre-ADSC treatment significantly maintained blood glucose homeostasis, reduced insulin resistance, promoted islet regeneration, and ameliorated the complications related to diabetes in rats (chronic kidney disease, non-alcoholic steatohepatitis, lung fibrosis, and cataract) compared to the ADSC group (P < 0.05). Additionally, the number of anti-inflammatory M2 macrophage phenotypes was enhanced in tissues following pre-ADSC injections. Moreover, the expression of pro-inflammatory genes (iNOS, TNF-alpha, IL-1beta) was reduced whereas that of anti-inflammatory genes (Arg1, CD206, and Il-10) was increased after cultivation with pre-ADSCs. Conclusion Diabetic microenvironment-preconditioned ADSCs effectively strengthen the capacity against inflammation and modulate the progress of long-term T2D complications. Keywords: Diabetes, Diabetes complications, Mesenchymal stem cells, Diabetic microenvironment precondition
Gitelman Syndrome (GS) patients frequently exhibit disrupted glucose metabolism, attributed to hypokalemia, hypomagnesemia and heightened aldosterone. This study delved into the genetic underpinnings ...linked to insulin resistance and diabetes in a GS patient, contextualized within his family history.
The hydrochlorothiazide and furosemide loading test were performed to ascertain the presence of GS. Oral glucose tolerance test (OGTT) evaluated glucose metabolism and insulin sensitivity. Whole-exome sequencing, validated by Sanger sequencing, was employed to confirm gene mutations, which were then tracked among the patient's relatives.
Symptoms and laboratory examination confirmed the clinical diagnosis of GS. Comprehensive whole-exome sequencing, augmented by Sanger sequencing validation, revealed a compound heterozygous mutation within the SLC12A3 gene (c.1108G>C in exon 9, c.676G>A in exon 5 and c.2398G>A in exon 20) in the patient. The OGTT affirmed diabetes and heightened insulin resistance, distinct from previous patients with GS we evaluated. Further genetic analysis identified a missense heterozygous mutation (c.97C>G in exon 1) within the PDX1 gene, inherited from the patient's diabetic mother without GS. Furthermore, the patient's brother, with impaired glucose tolerance but regular potassium levels, also bore this mutation, hinting at additional impacts of the PDX1 gene mutation on glucose metabolism regulation beyond the known impacts of GS.
This study unveils unprecedented compound heterozygous mutations in the SLC12A3 and PDX1 genes in a GS patient. These findings illuminate the potential complex genetic factors influencing glucose metabolism disruptions in GS.
This research uncovers a novel combination of SLC12A3 and PDX1 gene mutations in a Gitelman Syndrome patient, revealing intricate genetic factors that potentially disrupt glucose metabolism and shedding light on familial diabetes links.
Mesenchymal stem cells (MSCs) have emerged as a promising therapy for type 2 diabetes (T2D). Mechanistic researches demonstrate that the anti-diabetic effect of MSCs is partially mediated by ...eliciting macrophages into an anti-inflammatory phenotype thus alleviating insulin resistance. However, single MSC infusion is insufficient to ameliorate sustained hyperglycemia or normalize blood glucose levels. In this study, we used decitabine (DAC), which is involved in the regulation of macrophage polarization, to test whether MSCs combined with decitabine can prolong and enhance the anti-diabetic effect in T2D mice.
High-fat diet (HFD) and streptozocin (STZ) were given to induce T2D mouse model. Successfully induced T2D mice were randomly divided into four groups: T2D group, MSC group, DAC group, and MSC + DAC group. Blood glucose was monitored, and glucose tolerance and insulin sensitivity were evaluated during the entire analysis period. Epididymal fat was extracted for analysis of macrophage phenotype and inflammation in adipose tissue. In vitro, we examined the effect of MSC + DAC on macrophage polarization in bone marrow-derived macrophages (BMDMs) and explore the possible mechanism.
MSC infusion effectively improved insulin sensitivity and glucose homeostasis in T2D mice within 1 week, whereas combination therapy of MSCs + DAC extended the anti-diabetic effects of MSCs from 1 to 4 weeks (the end of the observation). Correspondingly, more M2 macrophages in adipose tissue were observed in the combination therapy group over the entire study period. In vitro, compared with the MSC group, MSCs combined with decitabine more effectively polarized M1 macrophages to M2 macrophages. Further analysis showed that the effect of MSC + DAC on macrophage polarization was largely abrogated by the peroxisome proliferator-activated receptor gamma (PPARγ) antagonist GW9662.
Our data suggest that MSCs combined with decitabine can more effectively alleviate insulin resistance and prolong and enhance the anti-diabetic effect of MSCs in T2D mice in part by prompting M2 polarization in a PPARγ-dependent manner. Thus, decitabine may be an applicable addition to MSCs for diabetes therapy. UC-MSCs combined with decitabine activate the IL4R/STAT6/STAT3/PPARγ axis to further promote M2 macrophage polarization in adipose tissue, reduce inflammation, improve insulin sensitivity, and lead to better glucose metabolism and long-term hypoglycemic effects.
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