Exploring the active components and potential mechanisms of Alpiniae oxyphyllae Fructus in treating diabetes mellitus with depression by UPLC-Q-Exactive Orbitrap/MS, network pharmacology and molecular docking.

The growing incidence of diabetes mellitus (DM) and depression is a global public health issue. Alpiniae oxyphyllae Fructus (AOF) is a kind of medicinal and edible plant which be found with anti-diabetic property, and could improve depression-like symptoms. This study aimed to screen active targets and potential mechanisms of AOF in treating DM with depression. Injection of streptozotocin (STZ) and exposure to chronic unpredictable mild stress (CUMS) for 4 weeks were used to conduct the DM with depression mice model. Behavioral tests, indexes of glucose metabolism, monoamine neurotransmitters, inflammatory cytokine and oxidative stress were measured. Histopathological change of hippocampus tissue was observing by HE and Nissl staining. UPLC-Q-Exactive Orbitrap/MS, network pharmacology and molecular docking were used to explore the chemical components and mechanisms of AOF on the DM with depression. AOF showed a reversed effect on body weight in DM with depression mice. Glucose metabolism and insulin resistance could be improved by treatment of AOF. In addition, AOF could alleviate depression-like behaviors based on the results of behavior tests and monoamine neurotransmitters. AOF also attenuated STZ-CUMS induced neuron injury in hippocampus. Next, a total of 61 chemical components were identified in the UPLC-Q-Exactive Orbitrap/MS analysis of the extract of AOF. Network pharmacology analysis suggested that 12 active components and 227 targets were screened from AOF, and 1802 target genes were screened from DM with depression, finally 126 intersection target genes were obtained. Drug-disease targets network was constructed and implied that the top five components with a higher degree value includes quercetin, nootkatone, baicalein, (-)-epicatechin and nootkatol. Protein-protein interaction (PPI) network showed that MAPK1, FOS, AKT1, IL6 and TP53 may be the core intersection targets. The mechanism of the effect of AOF on DM with depression was analyzed through gene ontology (GO), and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, mainly involved in AGE/RAGE, PI3K/AKT, and MAPK signaling pathways. The results of molecular docking indicated that quercetin, nootkatone, baicalein, (-)-epicatechin and nootkatol all had good binding to the core intersection targets. Overall, our experimental researches have demonstrated that AOF could exert the dual effects of anti-diabetic and anti-depression on DM with depression mice, through multi-targets and multi-pathways.

Mitochondrial unfolded protein response mechanism and its cardiovascular protective effects.

The mitochondrial unfolded protein response (UPRmt) is a cytoprotective response in response to cellular stress that is activated in response to mitochondrial stress to maintain intra-protein homeostasis, thereby protecting the cell from a variety of stimuli. The activation of this response has been linked to cardiovascular diseases. Here, we reviewed the current understanding of UPRmt and discussed its specific molecular mechanism, mainly in mammals, as well as addressing its protective role against cardiovascular diseases, so as to provide direction for further research on UPRmt and therapies targeting cardiovascular diseases in the future.

Genome-Wide Identification and Characterization of Homeobox Transcription Factors in Phoma sorghina var. saccharum Causing Sugarcane Twisted Leaf Disease.

A homeobox transcription factor is a conserved transcription factor, ubiquitous in eukaryotes, that regulates the tissue formation of structure, cell differentiation, proliferation, and cancer. This study identified the homeobox transcription factor family and its distribution in Phoma sorghina var. saccharum at the whole genome level. It elucidated the gene structures and evolutionary characteristics of this family. Additionally, knockout experiments were carried out and the preliminary function of these transcription factors was studied. Through bioinformatics approaches, nine homeobox transcription factors (PsHOX1-PsHOX9) were identified in P. sorghina var. saccharum, and these contained HOX-conserved domains and helix-turn-helix secondary structures. Nine homeobox gene deletion mutants were obtained using the homologous recombinant gene knockout technique. Protoplast transformation was mediated by polyethylene glycol (PEG) and the transformants were identified using PCR. The knockouts of PsHOX1, PsHOX2, PsHOX3, PsHOX4, PsHOX6, PsHOX8, and PsHOX9 genes resulted in a smaller growth diameter in P. sorghina var. saccharum. In contrast, the knockouts of the PsHOX3, PsHOX6, and PsHOX9 genes inhibited the formation of conidia and led to a significant decrease in the pathogenicity. This study's results will provide insights for understanding the growth and development of P. sorghina var. saccharum. The pathogenic mechanism of the affected sugarcane will provide an essential theoretical basis for preventing and controlling sugarcane twisted leaf disease.

Effects of mindfulness-based interventions on cardiovascular risk factors: An umbrella review of systematic reviews and meta-analyses.

OBJECTIVE: Reviews have shown that mindfulness-based interventions (MBIs) were effective in improving cardiovascular risk factors (CVRFs), but the results were contradictory. This umbrella review aimed to summarize and grade the existing reviews on CVRFs associated with MBIs. METHODS: The protocol of this umbrella review had been registered in PROSPERO (CRD42022356812). PubMed, Web of science, Embase, The Cochrane Library, Scopus, Medline, PsycINFO and CINAHL were searched from database inception to 20 July 2022. The quality of evidence was assessed through GRADE. RESULTS: Twenty-seven reviews with 14,923 participants were included. Overall, 45% of reviews had low heterogeneity (I2 < 25%). For the quality of evidence, 31% were rated very low, 42% were rated low, 17% were rated moderate and 10% were rated high. MBIs significantly improved systolic blood pressure [SMD -5.53 mmHg (95% CI -7.81, -3.25)], diastolic blood pressure [SMD -2.13 mmHg (95% CI -2.97, -1.30)], smoking [Cohen's d 0.42 (95% CI 0.20, 0.64)], glycosylated hemoglobin [MD 0.01 (95% CI -0.43, -0.07)], binge eating behavior [SMD -6.49 (95% CI -10.80, -2.18)], depression [SMD -0.72 (95% CI -1.23, -0.21)] and stress [SMD -0.67 (95% CI -1.00, -0.34)]. CONCLUSIONS: In conclusion, this umbrella review provided evidence for the role of MBIs in the improvement of CVRFs.

Fermented foods and metabolic outcomes in diabetes and prediabetes: A systematic review and meta-analysis of randomized controlled trials.

Several randomized controlled trials (RCTs) have investigated the effects of fermented foods on metabolic outcomes in adult patients suffering from diabetes and prediabetes. However, the results of these RCTs are conflicting. This systematic review and meta-analysis was carried out on data from RCTs to evaluate the effects of fermented foods in patients with diabetes and prediabetes. The PubMed, Web of Science, Embase, the Cochrane Library and Scopus databases were searched up to 21 June, 2022. English-language RCTs of fermented foods consumption were included which gave metabolic outcomes on body composition, glucose control, insulin sensitivity, lipid profile, as well as blood pressure. Eighteen RCTs met the inclusion criteria and 843 participants were included in the final analysis. The pooled results showed a significant reduction of fasting blood glucose (FBG), the homeostatic model assessment of insulin resistance (HOMA-IR), total cholesterol (TC), low density lipid cholesterol (LDL-C) and diastolic blood pressure (DBP) in the intervention group versus the control group. The results of this research showed that fermented foods have the potential to improve some metabolic outcomes, including FBG, HOMA-IR, TC, LDL-C, and DBP in patients with diabetes and prediabetes.

The effect of tomato and lycopene on clinical characteristics and molecular markers of UV-induced skin deterioration: A systematic review and meta-analysis of intervention trials.

Lycopene as a natural antioxidant that have been studied for ultraviolet radiation (UVR) photo protection and is one of the most effective carotenoids to scavenge reactive oxygen species (ROS). This review aims to summarize the protective effect of tomato and lycopene on skin photo damage and skin photoaging in healthy subjects by reviewing the existing population intervention experiments. A total of five electronic databases including PubMed, Scopus, EBSCO, Web of Science and Cochrane Library were searched from inceptions to January 2021 without any restriction. Out of 19336 publications identified, 21 fulfilled the inclusion criteria and were meta-analysis. Overall, interventions supplementing tomato and lycopene were associated with significant reductions in Δa*, MMP-1, ICAM-1 and skin pigmentation; while tomato and lycopene supplementation were associated with significant increase in MED, skin thickness and skin density. Based on the results of this systematic review and meta-analysis, supplementation with tomato and lycopene could reduce skin erythema formation and improve the appearance and pigmentation of the skin, thereby preventing light-induced skin photodamage and skin photoaging. Lycopene-rich products could be used as endogenous sun protection and may be a potential nutraceutical for sun protection.

Effects of fermented dairy products on inflammatory biomarkers: A meta-analysis.

AIM: Fermented dairy products (FDPs) are made from raw milk under the action of specific microorganisms by lactic acid bacteria fermentation or co-fermentation of lactic acid bacteria, bifidobacteria, and yeast. The aim of this study was to explore the effects of FDPs on inflammatory biomarkers. DATA SYNTHESIS: A comprehensive search was conducted on four electronic databases, including PubMed, Web of Science, Embase, and the Cochrane Library. Finally, fourteen trials (15 arms) were included in this meta-analysis: yogurt (n = 9), fermented milk (n = 4), and kefir (n = 2). Additionally, the random effects model or fixed-effects model was used to pool the study results. Firstly, the analysis indicated that FDPs' supplementation decreased the levels of C-reactive protein (CRP) (SMD = -0.21; 95% CI: -0.40, -0.02; P = 0.033) and increased interferon-gamma (IFN-γ) levels (SMD = 0.12; 95% CI: 0.01, 0.23; P = 0.033). Furthermore, we obtained some statistically significant results in the following subgroups: CRP decreased in participants with metabolic diseases. IFN-γ increased in the intervention that lasted ≥12 weeks, Asian, yogurt, and healthy population. Finally, there was no significant effect on tumor necrosis factor-alpha, interleukin (IL)-6, IL-10, and IL-2. CONCLUSIONS: FDPs reduced CRP and increased IFN-γ, but they had no effect on other inflammatory markers. The results showed that the consumption of FDPs was slightly associated with reduced inflammation, but because of the limited literature, these results should be interpreted with caution.

Zingiberaceae plants/curcumin consumption and multiple health outcomes: An umbrella review of systematic reviews and meta-analyses of randomized controlled trials in humans.

This umbrella review is to recapitulate and grade the available evidence of associations between consumption of Zingiberaceae plants/curcumin (Cur) and multiple health-related outcomes. This study included 161 meta-analyses of randomized controlled trials in 76 articles with 67 unique health outcomes. Data on heterogeneity and publication bias are considered to assess the quality of evidence. Based on the different impact of Zingiberaceae plants/Cur on human health, the advantages outweigh the disadvantages. Zingiberaceae plants/Cur can mainly improve metabolic syndrome, non-alcoholic fatty liver disease, cardiovascular disease, and some chronic inflammatory diseases, likewise, obviously relief the pain of osteoarthritis and related diseases. Ginger supplements have been shown to improve vomiting during pregnancy and to relieve nausea and vomiting caused by chemotherapy and surgery. The surgery is any type of surgery, including laparoscopic surgery, gynecological surgery and mixed surgery. Beneficial associations were found with Cur intervention in gastrointestinal, neurological and oral diseases. Zingiberaceae plants/Cur are generally safe and favorable for multiple health outcomes in humans. High-quality research is further needed to prove the observed associations.

Effects of cocoa products intake on cardiometabolic biomarkers of type 2 diabetes patients: a systematic review and meta-analysis based on both long-term and short-term randomised controlled trials.

Cocoa consumption as a diet has been shown to improve cardiometabolic biomarkers for T2D, but results were inconsistent. A comprehensive search from PubMed, Web of Science, Embase, and The Cochrane Library to identify the randomised controlled trials investigating the impacts of cocoa products consumption on cardiometabolic biomarkers in T2D was performed up to December 2020. Twelve trials involving 9 long-term and 3 short-term studies were included. The cocoa products significantly decreased low density lipoprotein-cholesterol (WMD: -9.955 mg/dL, 95% CI: -17.408, -2.501, p = 0.009), triglyceride (WMD: -15.364 mg/dL, 95% CI: -23.383, -7.346, p < 0.001), blood glucose (WMD: -9.105 mg/dL, 95% CI: -15.022, -3.189, p = 0.003), and C-reactive protein (WMD: -0.978 mg/L, 95% CI: -1.687, -0.269, p = 0.007) in long-term. The results indicated the beneficial long-term effects of cocoa products intake on cardiometabolic biomarkers for T2D, especially on blood glucose, lipid metabolism (LDL-C and TG), and inflammation (CRP).

Effects of medical plants from Zingiberaceae family on cardiovascular risk factors of type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials.

We performed a meta-analysis on randomized controlled trials (RCTs) to evaluate the efficacy of Zingiberaceae on cardiovascular risk factors in type 2 diabetes mellitus (T2DM). PubMed, Web of Science, Embase, The Cochrane Library, and Scopus were searched systematically until October 18, 2021. Thirty-four RCTs with 2154 patients met our inclusion. Pooled analysis indicated that Zingiberaceae can significantly improve body weight (BW) (WMD = -1.012, 95% CI: -1.673, -0.351, p = .003), fasting blood glucose (FBG) (WMD = -14.292, 95% CI: -18.588, -9.995, p < .001), glycosylated hemoglobin 1c (HbA1c) (WMD = -0.432, 95% CI: -0.607, -0.257, p < .001), serum insulin (WMD = -2.036, 95% CI: -2.857, -1.216, p < .001), homeostasis model assessment insulin resistance (HOMA-IR) (WMD = -0.886, 95% CI: -1.375, -0.398, p < .001), high density lipoprotein-cholesterol (HDL-C) (WMD = 0.850, 95% CI: 0.018, 1.682, p = .045), triglyceride (TG) (WMD = -17.636, 95% CI: -27.121, -8.151, p < .001), diastolic blood pressure (DBP) (WMD = -0.642, 95% CI: -1.148, -0.137, p = .013), C-reactive protein (CRP) (WMD = -0.623, 95% CI: -1.061, -0.186, p = .005), tumor necrosis factor-α (TNF-α) (WMD = -3.020, 95% CI: -4.327, -1.712, p < .001), and interleukin 6 (IL-6) (WMD = -1.147, 95% CI: -1.887, -0.406, p = .002). The supplementation of Zingiberaceae may be an effective adjunctive therapy in management of T2DM and prevention cardiovascular complications by decreasing BW, improving blood glucose control, insulin resistance, lipid profiles (HDL-C and TG), blood pressure (DBP), and reducing inflammation (CRP, TNF-α, and IL-6). PRACTICAL APPLICATIONS: Approximately half of the deaths of individuals with diabetes mellitus (DM) are attributable to cardiovascular disease (CVD), and individuals with T2DM have a two-fold increased risk of cardiovascular mortality than healthy individuals. Currently, T2DM is mainly treated with hypoglycemic medication such as sulfonylureas, thiazolidinediones, meglitinides, and biguanides. Nevertheless, most of them with long-term usage could cause side effects, including hypoglycemia and gastrointestinal troubles. Several species of the Zingiberaceae family are used in traditional herbal medicines, which have been widely used in traditional and complementary medicine. Proving the potential benefits of Zingiberaceae on T2DM and its cardiovascular complications has positive clinical implications for the use of this practical herb.

Flavonoid constituents of Amomum tsao-ko Crevost et Lemarie and their antioxidant and antidiabetic effects in diabetic rats - in vitro and in vivo studies.

Amomum tsao-ko Crevost et Lemarie (A. tsao-ko) is a well-known dietary spice and traditional Chinese medicine. This study aimed to identify the flavonoids in A. tsao-ko and evaluate their antioxidant and antidiabetic activities in in vitro and in vivo studies. A. tsao-ko methanol extracts possessed a high flavonoid content (1.21 mg QE per g DW) and a total of 29 flavonoids were identified by employing UPLC-MS/MS. In vitro, A. tsao-ko demonstrated antioxidant activity (ORAC value of 34276.57 µM TE/100 g DW, IC50 of ABTS of 3.49 mg mL-1 and FRAP value of 207.42 µM Fe2+ per g DW) and α-amylase and α-glucosidase inhibitory ability with IC50 values of 14.23 and 1.76 mg mL-1, respectively. In vivo, type 2 diabetes mellitus (T2DM) models were induced by a combined high-fat diet (HFD) and streptozotocin (STZ) injection in rats. Treatment with the A. tsao-ko extract (100 mg freeze-dried powder per kg bw) for 6 weeks could significantly improve impaired glucose tolerance, decrease the levels of fasting blood glucose (FBG), insulin, and malondialdehyde (MDA), and increase the superoxide dismutase (SOD) level. Histopathology revealed that the A. tsao-ko extract preserved the architecture and function of the pancreas. In conclusion, the flavonoid composition of A. tsao-ko exhibits excellent antioxidant and antidiabetic activity in vitro and in vivo. A. tsao-ko could be a novel natural material and developed as a related functional food and medicine in T2DM management.

Expression of single-chain Fv gene specific for gamma-seminoprotein by RTS and its biological activity identification.

Fabricating a single-chain variable fragment specific for human seminoprotein is very important in antibody-directed enzyme prodrug therapy and NMR imaging for prostate cancer. Here a single-chain Fv specific for gamma-seminoprotein was expressed by RTS. Its activity and the efficiency of entry into prostate cancer cells are investigated by immunoprecipitation and Western blotting and immunofluorescent staining, as well as entry of conjugated magnetic beads into cells. Results showed that ScFv peptides specific for gamma-seminoprotein were successfully prepared, which can bind with the prostate cells specifically and can bring magnetic beads into prostate cancer cells within 15 min, the amount of magnetic beads inside prostate cancer cells increased as the culture time prolonged. ScFv-conjugated magnetic beads did not enter into control cells. In conclusion, the ScFv peptide against human gamma-seminoprotein with biological activity was successfully fabricated, which can take magnetic beads to prostate cancer cells specifically and not to the control cells. This ScFv peptide against human gamma-seminoprotein should be useful in improving the detection and therapy of prostate cancer at early stages and NMR imaging.