The Chemical Signatures of Water Extract of Zingiber officinale Rosc.

Background: Ginger (Z. officinale Rosc.) is a common herb and is widely used as a diet-based or home therapy in traditional medicine worldwide. However, fresh ginger turns into dried ginger after kiln drying and shows a different treatment effect in clinical practice. Objective: To characterize the changes of major bioactive constituents in dried ginger after the processing of fresh ginger. Methods: A novel, ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC−QTOF/MS) method was established to characterize the changes in the bioactive constituents of dried ginger. The novel strategy was split into two steps: firstly, the MS selected the most intense precursor ions of tandem MS; then, target MS/MS acquisition with different collision energies (10, 20, and 40 eV) was used to characterize the compound's accurate MS/MS spectra and compare the MS/MS spectrum with the building MS reference library and reference standards. Result: Fifty-three compounds, including diarylheptanoids, gingerols, gingerodiols, gingerdiones, and shogaol-related compounds, were identified based on summarized fragmentation patterns. Fifteen out of fifty-three compounds were diarylheptanoids, which was different from fresh ginger. Conclusion: These identified compounds could be used to characterize the quality of dried ginger, pharmacologic studies should focus on diarylheptanoids explaining the different treatment effects between fresh ginger and dried ginger.

Elevated expression of ICAM-1 in synovium is associated with early inflammatory response for cartilage degeneration in type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is increasingly being recognized as an independent risk factor for the onset and progression of osteoarthritis (OA). Extensive studies have focused on the contribution of obesity (excessive mechanical stress), comorbidity frequently found in T2DM, to cartilage destruction during OA development. However, a little is known about how diabetes-related inflammation may affect the local cartilage in a diabetic objective. In the present study, we were able to establish a T2DM rat model using a combination of a low dose of streptozotocin with high-fat and high-sugar diet. Although the cartilage integrity was comparable between the control and T2DM groups, the expression of matrix metalloproteinases-13 (MMP-13) was significantly upregulated in T2DM, indicating the initiation of an early cascade of cartilage degeneration. In parallel, an obvious alteration of subchondral bone remodeling (inhibition of bone formation) was observed, as evidenced by the reduction of osterix-expressing positive cells. Moreover, we demonstrated that the expression of intercellular adhesion molecule-1 (ICAM-1) in the serum and synovium of T2DM rats was elevated, accompanied by an increase of synovitis score. We also noticed that the number of F4/80-positive macrophage cells was significantly increased in the T2DM group. Mechanistically, the expression of ICAM-1 in fibroblast-like synoviocytes can be triggered by glucose and interleukin-1ß, which are the two important factors within the joint of T2DM. Given that MMP-13 expression was significantly upregulated in the T2DM cartilage, and that ICAM-1-mediated filtration of macrophage was associated with synovitis, we propose that ICAM-1 is essential for triggering a vicious cycle of inflammation within the joint, which together subsequently drivers the cartilage degradation.

Differential expression of immune-related genes between healthy volunteers and type 2 diabetic patients with spleen-deficiency pattern.

OBJECTIVE: To investigate the clinical differentia tion of spleen-deficiency pattern (SDP), a group of symptoms and signs defined in terms of Traditional Chinese Medicine for its clinical practice. METHODS: Peripheral venous blood (> 3 mL) was collected from each of six type 2 diabetes mellitus (T2DM)-SDP patients and six healthy volunteers. After the isolation of peripheral white blood cells (PWBCs), total RNA was extracted, and quality control was performed on all RNA samples. Microarray experiments were conducted using the Agilent human whole genome gene chip, and genes demonstrating differential expression were screened. Bioinformatics analysis was conducted on these genes using several online databases. RESULTS: We screened a total of 175 differentially expressed genes (DEGs), of which 111 (63%) were down-regulated and 64 (37%) were up-regulated in T2DM-SDP patients compared with healthy controls. Among the 175 genes, 158 had biological function annotations: 46 (29%) were directly related to an individual's immune regulation or response, 25 (16%) were associated with substance and energy metabolism of PWBCs which could also indirectly influence immunity, and the remaining 87 (55%) were involved in a variety of PWBC biological processes that might eventually influence the immune function. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that the DEGs were predominantly enriched in seven immune-related pathways. Hierarchical cluster analysis identified gene expression patterns that were distinguishable between the two study groups. CONCLUSION: Our results suggest that T2DM-SDP patients experience significant hypoimmunity and/or immune dysfunctions, and possess a specific gene expression profile. These findings offer new insights into SDP and the clinical pattern differentiation of T2DM-SDP.

Diosgenin alleviates the inflammatory damage and insulin resistance in high glucose­induced podocyte cells via the AMPK/SIRT1/NF­κB signaling pathway.

Diabetic nephropathy (DN) is the predominant cause of end-stage renal disease globally. Diosgenin (DSG) has been reported to play a protective role in podocyte injury in DN. The present study aimed to explore the role of DSG in DN, as well as its mechanism of action in a high glucose (HG)-induced in vitro model of DN in podocytes. Cell viability, apoptosis, inflammatory response and insulin-stimulated glucose uptake were evaluated using Cell Counting Kit-8, TUNEL, ELISA and 2-deoxy-D-glucose assay, respectively. In addition, the expression of AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/NF-κB signaling-related proteins in podocyte cells was measured using western blotting. The results indicated that DSG enhanced the viability of podocytes after HG exposure, but inhibited inflammatory damage and attenuated insulin resistance. Moreover, DSG induced the activation of the AMPK/SIRT1/NF-κB signaling pathway. Furthermore, treatment with compound C, an inhibitor of AMPK, counteracted the protective effects of DSG on HG-induced podocyte cells. Therefore, DSG may be a potential therapeutic compound for the treatment of diabetic nephropathy.

Berberine Alleviates the Damage, Oxidative Stress and Mitochondrial Dysfunction of PC12 Cells Induced by High Glucose by Activating the KEAP1/Nrf2/ARE Pathway.

Diabetic encephalopathy (DE) is one of the major chronic complications of diabetes mellitus. This study aims to investigate the inhibitory effect of berberine (BBR) on the damage of PC12 cells induced by high glucose (HG). Differentiated PC12 cells were treated with different concentrations of glucose/BBR. The cell morphology, cell viability, lactate dehydrogenase (LDH) activity, apoptosis, oxidative stress (OS), mitochondrial structure, mitochondrial membrane potential (MMP), mitochondrial complex I-V activity, and adenosine triphosphate (ATP) levels were evaluated. The mRNA and protein levels of the Keap1/Nrf2/ARE pathway-related genes were assessed by RT-qPCR and Western blot. High-dose BBR and HG jointly treated-PC12 cells were treated with Nrf2-specific inhibitor ML385 to further verify whether Nrf2 was the target of BBR. The results showed that BBR inhibited cell damage, OS, and mitochondrial dysfunction induced by HG. The inhibitory effect of high BBR was more significant. The Keap1/Nrf2/ARE pathway was inhibited in PC12 cells induced by HG. BBR could activate the Keap1/Nrf2/ARE pathway, thus up-regulating the expression levels of antioxidant enzymes. ML385 antagonized the ameliorating effect of BBR on OS and mitochondrial dysfunction. The conclusion is that BBR can activate the Keap1/Nrf2/ARE pathway, upregulate the expression patterns of antioxidant enzymes, and reduce cell damage, OS, and mitochondrial dysfunction of PC12 cells induced by HG.

Rhein alleviates advanced glycation end products (AGEs)-induced inflammatory injury of diabetic cardiomyopathy in vitro and in vivo models.

In diabetic patients, diabetic cardiomyopathy (DCM) is one of the most common causes of death. The inflammatory response is essential in the pathogenesis of DCM. Rhein, an anthraquinone compound, is extracted from the herb rhubarb, demonstrating various biological activities. However, it is unclear whether rhein has an anti-inflammatory effect in treating DCM. In our research, we investigated the anti-inflammatory properties as well as its possible mechanism. According to the findings in vitro, rhein could to exert an anti-inflammatory effect by reducing the production of NO, TNF-α, PGE2, iNOS, and COX-2 in RAW264.7 cells that had been stimulated with advanced glycosylation end products (AGEs). In addition, rhein alleviated H9C2 cells inflammation injury stimulated by AGEs/macrophage conditioned medium (CM). In vivo have depicted that continuous gavage of rhein could improve cardiac function and pathological changes. Moreover, it could inhibit the accumulation of AGEs and infiltration of inflammatory factors inside the heart of rats having DCM. Mechanism study showed rhein could suppress IKKß and IκB phosphorylation via down-regulating TRAF6 expression to inhibit NF-κB pathway in AGEs/CM-induced H9C2 cells. Moreover, the anti-inflammation effect of rhein was realized through down-regulation phosphorylation of JNK MAPK. Furthermore, we found JNK MAPK could crosstalk with NF-κB pathway by regulating IκB phosphorylation without affecting IKKß activity. And hence, the protective mechanism of rhein may involve the inhibiting of the TRAF6-NF/κB pathway, the JNK MAPK pathway, and the crosstalk between the two pathways. These results suggested that rhein may be a promising drug candidate in anti-inflammation and inflammation-related DCM therapy.

Behavioral Prevention, Treatment, and Rehabilitation of Using Western and Chinese Medicines or Herbal Products among the Public in Response to COVID-19 in Hong Kong: A Cross-Sectional Study.

The coronavirus disease 2019 (COVID-19) pandemic occurred in Hong Kong for more than two years. This article conducted a cross-sectional study for participants to investigate the behavioral prevention, treatment, and rehabilitation of using Western medicines or herbal products for COVID-19 in Hong Kong. A questionnaire was designed and performed over 2 weeks from 1 May to 15 May 2022. It consisted of five parts with around 20 questions conducted including sociodemographic information, prevention, treatment, rehabilitation of COVID-19, and also the sources of information. The pattern usage of Chinese or Western medicines for COVID-19 was studied after data collection. 318 people participated in this survey, and only 311 were qualified. The sociodemographic information, e.g., personal educational level, and behavior for the prevention of COVID-19, which included wearing masks (98.7%), using alcohol hand sanitizer (83.0%), washing hands frequently (82.4%), avoiding crowds (53.1%), and staying home more often (50.6%). Western medicines, such as antipyretic drugs, antitussive drugs, and pain reliever drugs, whilst Chinese medicines, such as Lianhua Qingwen Jiaonang, Huoxiang Zhengqi San or Wan, and Nin Jiom Pei Pa Koa, were most commonly used in the treatment and rehabilitation periods of COVID-19. Herbal products, including lemon, honey, ginger, and herbal tea, were used as a daily diet to fight against COVID-19. Based on the result findings, Chinese medicines or herbal products were used during the COVID-19 pandemic, but most of the participants used an unknown Chinese medicine practitioner's prescription and self-administered Chinese medicine. The pattern of Chinese medicines and Western medicines' usage in the prevention, treatment, and rehabilitation of COVID-19 was also investigated; this showed a statistically significant association between the variables according to gender, age, and Chinese or Western medicines for further investigation.

A Study of the Protective Effect of Bushen Huoxue Prescription on Cerebral Microvascular Endothelia Based on Proteomics and Bioinformatics.

Diabetic cognitive dysfunction is a serious complication of type 2 diabetes mellitus (T2DM), which can cause neurological and microvascular damage in the brain. At present, there is no effective treatment for this complication. Bushen Huoxue prescription (BSHX) is a newly formulated compound Chinese medicine containing 7 components. Previous research indicated that BSHX was neuroprotective against advanced glycosylation end product (AGE)-induced PC12 cell insult; however, the effect of BSHX on AGE-induced cerebral microvascular endothelia injury has not been studied. In the current research, we investigated the protective effects of BSHX on AGE-induced injury in bEnd.3 cells. Our findings revealed that BSHX could effectively protect bEnd.3 cells from apoptosis. Moreover, we analyzed the network regulation effect of BSHX on AGE-induced bEnd.3 cells injury at the proteomic level. The LC-MS/MS-based shotgun proteomics analysis showed BSHX negatively regulated multiple AGE-elicited proteins. Bioinformatics analysis revealed these differential proteins were involved in multiple processes, such as Foxo signaling pathway. Further molecular biology analysis confirmed that BSHX could downregulate the expression of FoxO1/3 protein and inhibit its nuclear transfer and inhibit the expression of downstream apoptotic protein Bim and the activation of caspase, so as to play a protective role in AGE-induced bEnd.3 injury. Taken together, these findings demonstrated the role of BSHX in the management of diabetic cerebral microangiopathy and provide some insights into the proteomics-guided pharmacological mechanism study of traditional Chinese Medicine.

Pro-Inflammatory diet accounts for higher prevalence of retinopathy in diabetes participants rather than normal glucose and prediabetes: Results from NHANES, 2005-2008.

Retinopathy is a chronic inflammatory disease whose prognosis could be improved with dietary interventions. However, the association between a pro-inflammatory diet and the prevalence of retinopathy has not been fully elucidated. We assess the association between the dietary inflammatory index (DII), which is a comprehensive index determining inflammatory potential derived from food parameters according to literature, and the prevalence of retinopathy based on the data from the National Health and Nutritional Examination Survey (NHANES) 2005-2008 involving 2,403 participants. Energy-adjusted DII (E-DII) was not related to the occurrence of retinopathy in the general, non-diabetic, or middle-aged participants. In the diabetic and aged participants, one unit increment of E-DII accounted for 14 and 15% higher the prevalence of retinopathy respectively. The highest E-DII group had a 78 and 79% higher prevalence of retinopathy than the lowest group respectively. After adjusting for several covariables, the highest E-DII group was still associated with a 68% increase in retinopathy in diabetic patients. These results suggest that E-DII is positively associated with the prevalence of diabetic retinopathy among diabetic patients.

Patient-Reported Outcomes Following the Use of Jiang Tang San Huang Tablets in Type 2 Diabetes Mellitus: A Retrospective Cohort Study in a Chinese Population.

Purpose: We aimed to assess the efficacy of the Jiang Tang San Huang (JTSH) tablet for the treatment of patients with type 2 diabetes mellitus (T2DM). Methods: All data for this retrospective cohort study were acquired from the outpatient clinic database of our institution, and all enrolled patients received JTSH tablet for at least two months. Overall, 147 patients were included in the analysis. The primary outcome was patient-reported outcomes on the efficacy of the JTSH tablets using a questionnaire survey. Correlation analysis evaluated the duration of JTSH tablet administration and glycemic control in patients with T2DM. The secondary outcome measures included: changes in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), 2-hour postprandial blood glucose, homeostasis model assessment of insulin resistance index (HOMA-IR) and homeostasis model assessment of ß-cell function (HOMA-ß) after 2 months of treatment with JTSH tablets. Results: Overall,120 patients (81.63%) reported a JTSH tablet treatment satisfaction score of ≥60 points, and believed that JTSH tablets had satisfactory hypoglycemic effects and could improve symptoms. The average duration of JTSH tablet treatment was 2.57±1.45 years. Overall, 111 patients achieved good blood glucose control, while 36 patients had poor glycemic control. Multivariate logistic regression model analysis showed that taking JTSH tablets for 1 year might reduce the risk of poor hypoglycemic effect by 17.00% (Risk ratio=0.830, 95% confidence interval:0.578, 1.021, P=0.066). Compared with the baseline data, the levels of HbA1c, FPG and HOMA-IR decreased significantly and HOMA-ß levels increased significantly (P<0.05). Conclusion: Good blood glucose control may be positively correlated with the duration of JTSH tablets administration. Patients with T2DM were satisfied with the anti-diabetic effects of JTSH tablets, which can significantly reduce blood glucose and insulin resistance, and improve the function of islet cells.

The Prognostic Value of Serum Apolipoprotein A-I Level and Neutrophil-to-Lymphocyte Ratio in Colorectal Cancer Liver Metastasis.

Background: Colorectal cancer liver metastasis (CRLM) is a high degree of malignancy with rapid disease progression and has a poor prognosis. Both serum apolipoprotein A-I (ApoA-I) and neutrophil-to-lymphocyte ratio (NLR) play key roles in anti-inflammation and antitumor. This study is aimed at evaluating the implication of serum ApoA-I level in combination with NLR in the prognosis of CRLM. Methods: We retrospectively analyzed the serum ApoA-I level and NLR in 237 patients with CRLM. Cox regression analyses were used to identify the independent prognostic significance of these indicators. Kaplan-Meier method and Log-rank test were applied to compute overall survival (OS). Both the ApoA-I and NLR were divided into three levels, according to their medians. A risk-stratified prediction model was established to evaluate the prognosis of patients with CRLM. The ROC curve AUC values were applied to evaluate the capability of the model. Results: Higher levels of ApoA-I and lower NLR were strongly associated with prolonged OS (Log-rank test, P < 0.05). The patients were then grouped into three queues according to the ApoA-I level and NLR. There was a crucial diversity in the OS (P < 0.001) between the high-risk (ApoA - I ≤ 1.03 g/L and NLR > 3.24), medium-risk (ApoA - I > 1.03 g/L or NLR ≤ 3.24) and low-risk groups (ApoA - I > 1.03 g/L and NLR ≤ 3.24). The AUC value of the prediction model (AUC = 0.623, 95% CI: 0.557-0.639, P = 0.001) was higher than other individual indicators (including ApoA-I, NLR, cT classification, and cN classification). Additionally, the association of the prediction model and cTN classification (AUC = 0.715, 95% CI: 0.606-0.708, P < 0.001) was better than the model and cTN classification alone. Conclusion: The combination of ApoA-I level and NLR could be a prognostic indicator for CRLM.

Procyanidin B2 Alleviates Palmitic Acid-Induced Injury in HepG2 Cells via Endoplasmic Reticulum Stress Pathway.

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome featuring ectopic lipid accumulation in hepatocytes. NAFLD has been a severe threat to humans with a global prevalence of over 25% yet no approved drugs for the treatment to date. Previous studies showed that procyanidin B2 (PCB2), an active ingredient from herbal cinnamon, has an excellent hepatoprotective effect; however, the mechanism remains inconclusive. The present study aimed to investigate the protective effect and underlying mechanism of PCB2 on PA-induced cellular injury in human hepatoma HepG2 cells. Our results showed that PA-induced oxidative stress, calcium disequilibrium, and subsequent endoplasmic reticulum stress (ERS) mediated cellular injury, with elevated protein levels of GRP78, GRP94, CHOP, and hyperphosphorylation of PERK and IRE1α as well as the increased ratio of Bax/Bcl-2, which was restored by PCB2 in a concentration-dependent manner, proving the excellent antiapoptosis effect. In addition, 4-phenylbutyric acid (4-PBA), the ER stress inhibitor, increased cell viability and decreased protein levels of GRP78 and CHOP, which is similar to PCB2, and thapsigargin (TG), the ER stress agonist, exhibited conversely meanwhile partly counteracted the hepatic protection of PCB2. What is more, upregulated protein expression of p-IKKα/ß, p-NF-κB p65, NLRP3, cleaved caspase 1, and mature IL-1ß occurred in HepG2 cells in response to PA stress while rescued with the PCB2 intervention. In conclusion, our study demonstrated that PA induces ERS in HepG2 cells and subsequently activates downstream NLRP3 inflammasome-mediated cellular injury, while PCB2 inhibits NLRP3/caspase 1/IL-1ß pathway, inflammation, and apoptosis with the presence of ERS, thereby promoting cell survival, which may provide pharmacological evidence for clinical approaches on NAFLD.

Identification of potential bioactive compounds and mechanisms of GegenQinlian decoction on improving insulin resistance in adipose, liver, and muscle tissue by integrating system pharmacology and bioinformatics analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: GegenQinlian Decoction (GQD), a classical formula in traditional Chinese medicine, is widely used in the treatment of diabetes. While studies have demonstrated that GQD is an efficacious treatment for insulin resistance (IR) in type 2 diabetes mellitus (T2DM), the potential bioactive compounds and mechanisms remain unclear. AIM OF THE STUDY: To further investigate the potential bioactive compounds, targets, and pathways of GQD on improving IR in T2DM for adipose, liver, and muscle tissue using an integrated strategy of system pharmacology and bioinformatics analysis. MATERIALS AND METHODS: We screened the candidate compounds and targets of GQD and identified IR-associated differentially expressed genes (DEGs) of adipose, liver, and muscle tissue, respectively. Then the intersecting target genes between candidate targets and DEGs were used for "GQD-compounds-targets-tissue" network construction in each type of tissue. The top 10 bioactive compounds acting on each type of tissue were intersected and consequently identified as potential bioactive compounds of GQD. Furthermore, pathway enrichment, protein-protein interaction (PPI) network construction, and hub target identification were performed based on the targets of GQD and the targets of quercetin in each type of tissue, respectively. Finally, to further confirm the role of quercetin, we intersected the hub targets of quercetin and the hub targets of GQD, and the pathways were intersected as well. RESULTS: 132 compounds and 119 potential targets of these compounds were obtained. 1,765, 3,206, and 3594 DEGs were identified between IR and insulin sensitivity (IS) tissue in adipose, liver, and muscle, respectively. There were 21, 23, 45 targets and 103, 73, 123 compounds in the "GQD-compounds-targets-tissue" network of adipose, liver, and muscle tissue, respectively. Then compounds such as quercetin, kaempferol, baicalein, wogonin, isorhamnetin, beta-sitosterol and licochalcone A, were identified as the potential bioactive compounds of GQD, and quercetin had the highest degree among the compounds. Moreover, based on the targets of GQD, hub targets like PPARG, RELA, EGFR, CASP3, VEGFA, AR, ESR1 and CCND1, and signaling pathways such as insulin signaling pathway, endocrine resistance, TNF signaling pathway, PI3K-Akt signaling pathway, AMPK signaling pathway, MAPK signaling pathway, NF-κB signaling pathway, HIF-1 signaling pathway, apoptosis, and VEGF signaling pathway, were filtered out as the underlying mechanisms of GQD on improving diabetic IR. In addition, the hub targets and pathways of quercetin coincided with most of the hub targets and pathways of GQD in each type of tissue, respectively, suggesting that quercetin may be a potential representative compound of GQD. CONCLUSIONS: Our analysis identifies the potential bioactive compounds, targets, and pathways of GQD on improving IR in T2DM for adipose, liver, and muscle tissue, which shows the characteristics of multi-compounds, multi-targets, multi-pathways, and multi-mechanisms of GQD and lays a solid foundation for further experimental research and clinical application.

SYmptom-Based STratification of DiabEtes Mellitus by Renal Function Decline (SYSTEM): A Retrospective Cohort Study and Modeling Assessment.

Background: Previous UK Biobank studies showed that symptoms and physical measurements had excellent prediction on long-term clinical outcomes in general population. Symptoms and signs could intuitively and non-invasively predict and monitor disease progression, especially for telemedicine, but related research is limited in diabetes and renal medicine. Methods: This retrospective cohort study aimed to evaluate the predictive power of a symptom-based stratification framework and individual symptoms for diabetes. Three hundred two adult diabetic patients were consecutively sampled from outpatient clinics in Hong Kong for prospective symptom assessment. Demographics and longitudinal measures of biochemical parameters were retrospectively extracted from linked medical records. The association between estimated glomerular filtration rate (GFR) (independent variable) and biochemistry, epidemiological factors, and individual symptoms was assessed by mixed regression analyses. A symptom-based stratification framework of diabetes using symptom clusters was formulated by Delphi consensus method. Akaike information criterion (AIC) and Bayesian information criterion (BIC) were compared between statistical models with different combinations of biochemical, epidemiological, and symptom variables. Results: In the 4.2-year follow-up period, baseline presentation of edema (-1.8 ml/min/1.73m2, 95%CI: -2.5 to -1.2, p < 0.001), epigastric bloating (-0.8 ml/min/1.73m2, 95%CI: -1.4 to -0.2, p = 0.014) and alternating dry and loose stool (-1.1 ml/min/1.73m2, 95%CI: -1.9 to -0.4, p = 0.004) were independently associated with faster annual GFR decline. Eleven symptom clusters were identified from literature, stratifying diabetes predominantly by gastrointestinal phenotypes. Using symptom clusters synchronized by Delphi consensus as the independent variable in statistical models reduced complexity and improved explanatory power when compared to using individual symptoms. Symptom-biologic-epidemiologic combined model had the lowest AIC (4,478 vs. 5,824 vs. 4,966 vs. 7,926) and BIC (4,597 vs. 5,870 vs. 5,065 vs. 8,026) compared to the symptom, symptom-epidemiologic and biologic-epidemiologic models, respectively. Patients co-presenting with a constellation of fatigue, malaise, dry mouth, and dry throat were independently associated with faster annual GFR decline (-1.1 ml/min/1.73m2, 95%CI: -1.9 to -0.2, p = 0.011). Conclusions: Add-on symptom-based diagnosis improves the predictive power on renal function decline among diabetic patients based on key biochemical and epidemiological factors. Dynamic change of symptoms should be considered in clinical practice and research design.

Identifying Type 2 Diabetic Brains by Investigating Disease-Related Structural Changes in Magnetic Resonance Imaging.

Diabetes with high blood glucose levels may damage the brain nerves and thus increase the risk of dementia. Previous studies have shown that dementia can be reflected in altered brain structure, facilitating computer-aided diagnosis of brain diseases based on structural magnetic resonance imaging (MRI). However, type 2 diabetes mellitus (T2DM)-mediated changes in the brain structures have not yet been studied, and only a few studies have focused on the use of brain MRI for automated diagnosis of T2DM. Hence, identifying MRI biomarkers is essential to evaluate the association between changes in brain structure and T2DM as well as cognitive impairment (CI). The present study aims to investigate four methods to extract features from MRI, characterize imaging biomarkers, as well as identify subjects with T2DM and CI.

Chrysophanol Alleviates Metabolic Syndrome by Activating the SIRT6/AMPK Signaling Pathway in Brown Adipocytes.

Chrysophanol, a primary active ingredient of Cassia mimosoides Linn or Rhei radix et rhizoma, has various pharmacological properties, including anticancer, antidiabetic, and anti-inflammatory, as well as blood lipid regulation. However, whether chrysophanol can mitigate obesity, and its underlying mechanisms remains unclear. This study investigated whether chrysophanol effects energy metabolism in high-fat diet- (HFD-) induced obese mice and fat-specific Sirtuin 6- (SIRT6-) knockout (FKO) mice, targeting the SIRT6/AMPK signaling pathway in brown and white fat tissue. Our results showed that chrysophanol can effectively inhibit lipid accumulation in vitro and reduce mice's body weight, improve insulin sensitivity and reduced fat content of mice, and induce energy consumption in HFD-induced obese mice by activating the SIRT6/AMPK pathway. However, a treatment with OSS-128167, an SIRT6 inhibitor, or si-SIRT6, SIRT6 target specific small interfering RNA, in vitro blocked chrysophanol inhibition of lipid accumulation. Similar results were obtained when blocking the AMPK pathway. Moreover, in the HFD-induced obese model with SIRT6 FKO mice, histological analysis and genetic test results showed that chrysophanol treatment did not reduce lipid droplets and upregulated the uncoupling protein 1 (UCP1) expression. Rather, it upregulated the expression of thermogenic genes and activated white fat breakdown by inducing phosphorylation of adenosine 5'-monophosphate- (AMP-) activated protein kinase (AMPK), both in vitro and in vivo. OSS-128167 or si-SIRT6 blocked chrysophanol's upregulation of peroxisome proliferator-activated receptor-γ coactivator-1α (Pgc-1α) and Ucp1 expression. In conclusion, this study demonstrated that chrysophanol can activate brown fat through the SIRT6/AMPK pathway and increase energy consumption, insulin sensitivity, and heat production, thereby alleviating obesity and metabolic disorders.