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Solute carriers (SLCs) constitute the largest superfamily of membrane transporter proteins. These transporters, present in various SLC families, play a vital role in energy metabolism by facilitating the transport of diverse substances, including glucose, fatty acids, amino acids, nucleotides, and ions. They actively participate in the regulation of glucose metabolism at various steps, such as glucose uptake (e.g., SLC2A4/GLUT4), glucose reabsorption (e.g., SLC5A2/SGLT2), thermogenesis (e.g., SLC25A7/UCP-1), and ATP production (e.g., SLC25A4/ANT1 and SLC25A5/ANT2). The activities of these transporters contribute to the pathogenesis of type 2 diabetes mellitus (T2DM). Notably, SLC5A2 has emerged as a valid drug target for T2DM due to its role in renal glucose reabsorption, leading to groundbreaking advancements in diabetes drug discovery. Alongside SLC5A2, multiple families of SLC transporters involved in the regulation of glucose homeostasis hold potential applications for T2DM therapy. SLCs also impact drug metabolism of diabetic medicines through gene polymorphisms, such as rosiglitazone (SLCO1B1/OATP1B1) and metformin (SLC22A1-3/OCT1-3 and SLC47A1, 2/MATE1, 2). By consolidating insights into the biological activities and clinical relevance of SLC transporters in T2DM, this review offers a comprehensive update on their roles in controlling glucose metabolism as potential drug targets.

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BackgroundPre-pandemic psychiatric disorders have been associated with an increased risk of COVID-19. However, the underlying mechanisms remain unknown, e.g. to what extent genetic predisposition to psychiatric disorders contributes to the observed association. MethodsThe analytic sample consisted of white British participants of UK Biobank registered in England, with available genetic data, and alive on Jan 31, 2020 (i.e., the start of the COVID-19 outbreak in the UK) (n=346,554). We assessed individuals genetic predisposition to different psychiatric disorders, including substance misuse, depression, anxiety, and psychotic disorder, using polygenic risk score (PRS). Diagnoses of psychiatric disorders were identified through the UK Biobank hospital inpatient data. We performed a GWAS analysis for each psychiatric disorder in a randomly selected half of the study population who were free of COVID-19 (i.e., the base dataset). For the other half (i.e., the target dataset), PRS was calculated for each psychiatric disorder using the discovered genetic variants from the base dataset. We then examined the association between PRS of each psychiatric disorder and risk of COVID-19, or severe COVID-19 (i.e., hospitalization and death), using logistic regression models. The ascertainment of COVID-19 was through the Public Health England dataset, the UK Biobank hospital inpatient data and death registers, updated until July 26, 2020. For validation, we repeated the PRS analyses based on publicly available GWAS summary statistics. Results155,988 participants (including 1,451 COVID-19 cases), with a mean age of 68.50 years at COVID-19 outbreak, were included for PRS analysis. Higher genetic liability forwards psychiatric disorders was associated with increased risk of both any COVID-19 and severe COVID-19, especially genetic risk for substance misuse and depression. The adjusted odds ratios (ORs) for any COVID-19 were 1.15 (95% confidence interval [CI] 1.02-1.31) and 1.26 (1.11-1.42) among individuals with a high genetic risk (above the upper tertile of PRS) for substance misuse and depression, respectively, compared with individuals with a low genetic risk (below the lower tertile). Largely similar ORs were noted for severe COVID-19 and similar albeit slightly lower estimates using PRSs generated from GWAS summary statistics from independent samples. ConclusionIn the UK Biobank, genetic predisposition to psychiatric disorders was associated with an increased risk of COVID-19, including severe course of the disease. These findings suggest the potential role of genetic factors in the observed phenotypic association between psychiatric disorders and COVID-19, underscoring the need of increased medical surveillance of for this vulnerable population during the pandemic.

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ObjectiveTo determine the association between pre-pandemic psychiatric disorders and the risk of COVID-19. DesignCommunity-based prospective cohort study. SettingUK Biobank population. Participants421,048 participants who were recruited in England and alive by January 31st 2020, i.e., the start of COVID-19 outbreak in the UK. 50,815 individuals with psychiatric disorders recorded in the UK Biobank inpatient hospital data before the outbreak were included in the exposed group, while 370,233 participants without such conditions were in the unexposed group. MeasurementsWe obtained information on positive results of COVID-19 test as registered in the Public Health England, COVID-19 related hospitalizations in the UK Biobank inpatient hospital data, and COIVD-19 related deaths from the death registers. We also identified individuals who was hospitalized for infections other than COVID-19 during the follow-up. Logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (CIs), controlling for multiple confounders. ResultsThe mean age at outbreak was 67.8 years and around 43% of the study participants were male. We observed an elevated risk of COVID-19 among individuals with pre-pandemic psychiatric disorder, compared with those without such diagnoses. The fully adjusted ORs were 1.44 (95%CI 1.27 to 1.64), 1.67 (1.42 to 1.98), and 2.03 (1.56 to 2.63) for any COVID-19, inpatient COVID-19, COVID-19 related death, respectively. The excess risk was observed across all levels of somatic comorbidities and subtypes of pre-pandemic psychiatric disorders, while further increased with greater number of pre-pandemic psychiatric disorders. We also observed an association between pre-pandemic psychiatric disorders and increased risk of hospitalization for other infections (1.85 [1.65 to 2.07]). ConclusionsPre-pandemic psychiatric disorders are associated with increased risk of COVID-19, especially severe and fatal COVID-19. The similar association observed for hospitalization for other infections suggests a shared pathway between psychiatric disorders and different infections, including altered immune responses. Summary boxO_ST_ABSWhat is already known on this topic?C_ST_ABSPsychiatric morbidities have been associated with risks of severe infections through compromised immunity and/or health-behaviors. While recent studies showed that unhealthy lifestyle and psychosocial factors (including self-reported psychological distress) increased the risk of COVID-19 hospitalization, data on the role of clinically confirmed psychiatric disorders in COVID-19 susceptibility are to date absent. What this study adds?Using the large community-based data in UK Biobank, our analysis is the first to demonstrate an increase in the risk of COVID-19, especially severe and fatal COVID-19, among individuals with pre-pandemic psychiatric disorders, independently of many important confounders. A similar association was also observed between pre-pandemic psychiatric disorder and hospitalization due to other infections during the COVID-19 outbreak, suggesting a shared pathway between psychiatric disorders and different infections, including altered immune responses. This finding underscores the need of surveillance and care in vulnerable populations with history of psychiatric disorders during the COVID-19 outbreak.

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Pyrroline-5-carboxylate reductase 1 (PYCR1) is an enzyme involved in cell metabolism and is upregulated in cancer. However, the correlations of PYCR1 expression with the clinicopathological features and prognosis of renal cell carcinoma (RCC) remain unclear. The purpose of this study was to identify the expression of PYCR1 and its clinical relevance in RCC patients.PYCR1 mRNA expression differences between RCC and the adjacent normal renal tissues were assessed using the Cancer Genome Atlas database (TCGA). Subsequently, the expression of PYCR1 mRNA and protein were evaluated by quantitative real-time polymerase chain reaction, Western blot, and immunochemistry using 30 paired frozen samples of RCC and the adjacent normal renal tissues. The protein expression of PYCR1 was evaluated by immunostaining formalin-fixed, paraffin-embedded sections of RCC samples from 96 patients who underwent radical nephrectomy, and its relationship with clinical features were analyzed. Nonpaired t tests were used to statistically analyze the differences between the 2 groups. Cox univariable and multivariable analyses of overall survival (OS) among RCC patients were performed.The expression of PYCR1 mRNA was significantly upregulated in RCC tissues compared to adjacent normal renal tissues in the TCGA database (P < .01). The area under the receiver operating characteristic curve value was 0.748. The expression of PYCR1 mRNA and protein was significantly upregulated in RCC compared with that in paired normal renal tissues (P < .01). Higher PYCR1 levels were associated with metastasis (P < .01). Kaplan-Meier survival curves indicated that higher PYCR1 expression was correlated with poorer OS. Therefore, PYCR1 may act as a novel prognostic marker and therapeutic target in the diagnosis and treatment of RCC.

Asunto(s)

Carcinoma de Células Renales/enzimología , Neoplasias Renales/enzimología , Pirrolina Carboxilato Reductasas/metabolismo , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Riñón/enzimología , Riñón/patología , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Pronóstico , ARN Mensajero/metabolismo , Análisis de Supervivencia , delta-1-Pirrolina-5-Carboxilato Reductasa

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OBJECTIVE:To establish the HPLC fingerprints for Huobahuagen tablets intermediate. METHODS:HPLC was per-formed on Inertsil ODS-4 column with mobile phase consisted of acetonitrile-0.1% phosphoric acid (gradient elution) at the flow rate of 0.75 mL/min. The detection wavelength was set at 220 nm,and column temperature was 30 ℃. The sample size was 10 μL. Using wilforgine as reference,HPLC chromatograms of 10 batches of samples were determined. Common peak identification and similarity evaluation were performed by using Similarity Evaluation System for TCM Chromatographic Fingerprint (2004 A edi-tion). RESULTS:There were 25 common peaks in HPLC chromatograms of 10 batches of samples,and similarity degrees were higher than 0.9. After validated,HPLC chromatograms of 10 batches of samples were in good agreement with control fingerprints. CONCLUSIONS:The established fingerprint can provide reference for identification and quality evaluation of Huobahuagen tab-lets intermediate.

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Ultrafine powder and cell wall-broken powder of herbal medicine lack of the morphological characters and microscopic identification features. This makes it hard to identify herb's authenticity with traditional methods. We tested ITS2 sequence as DNA barcode in identification of herbal medicine in ultrafine powder and cell wall-broken powder in this study. We extracted genomic DNAs of 93 samples of 31 representative herbal medicines (28 species), which include whole plant, roots and bulbs, stems, leaves, flowers, fruits and seeds. The ITS2 sequences were amplified and sequenced bidirectionally. The ITS2 sequences were identified using Basic Local Alignment Search Tool (BLAST) method in the GenBank database and DNA barcoding system to identify the herbal medicine. The genetic distance was analyzed using the Kimura 2-parameter (K2P) model and the Neighbor-joining (NJ) phylogenetic tree was constructed using MEGA 6.0. The results showed that DNA can be extracted successfully from 93 samples and high quality ITS2 sequences can be amplified. All 31 herbal medicines can get correct identification via BLAST method. The ITS2 sequences of raw material medicines, ultrafine powder and cell wall-broken powder have same sequence in 26 herbal medicines, while the ITS2 sequences in other 5 herbal medicines exhibited variation. The maximum intraspecific genetic-distances of each species were all less than the minimum interspecific genetic distances. ITS2 sequences of each species are all converged to their standard DNA barcodes using NJ method. Therefore, using ITS2 barcode can accurately and effectively distinguish ultrafine powder and cell wall-broken powder of herbal medicine. It provides a new molecular method to identify ultrafine powder and cell wall-broken powder of herbal medicine in the quality control and market supervision.

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This study was aimed to establish an Ultra Fast Liquid Chromatography-Photo Diode Array (UFLC-PDA) method for the simultaneous determination of five chemical components, which included chlorogenic acid, loganin, sweroside, evodia rutaecarpa glycosides and triplostoside A, in Pterocephalus hookeri h eck. Agilent Poroshell 120 SB-C18 (100 mm í 4.6 mm, 2.7 μm) was adopted, with acetonitrile-0.2% phosphoric acid solution in gradient elution as the mobile phase at the flow rate of 1.0 mL·min-1. And the injection volume was 0.4 μL. The detection wavelength was set up at 237 nm and 325 nm. And the column temperature was 30℃. The results showed that the calibration curve was linear within the range of 8.72~218.0, 1.52~38.0, 2.44~61.0, 29.36~734.0, 3.00~75.0μg·mL-1 (r > 0.999 6, n=9) for chlorogenic acid, loganin, sweroside, evodia rutaecarpa glycosides and triplostoside A, respectively. The average recovery rates were 99.46%, 99.41%, 100.14%, 98.89%, and 99.42%, respectively. The RSD was 0.69%, 0.66%, 0.60%, 1.21%, and 0.64%, respectively (n = 9). It was concluded that this method was simple, accurate and reproducible, which can be used for the simultaneous determination of the content of five chemical components in P. hookeri.

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The article was aimed to study the influence of low pressure and hypoxia on rat metabolism and evaluate the intervention effect of San-Guo-Tang-San (SGTS) on high altitude polycythemia (HAPC) rats. A total of 25 rats were divided into the plain control group, high altitude model group, Hong-Jing-Tian capsule (Nuo-Di-Kang cap-sule) group, high-dose SGTS group and low-dose SGTS group, with 5 rats in each group. After one week adaptation, rats in the model group and the medication groups were put into the hyperbaric chamber for 40 days (22 h/d) to simulate high altitude environment of 5 000 m. In the end of 40th day, the hemorheology and the dry/wet weight ratio of lung of rats were measured. And plasma samples were derivatized with ECF prior to GC-MS instrumental analysis. Principal component analysis (PCA) was used to find potential biomarkers, and evaluate the intervention effects of SGTS. The results showed that the low pressure and hypoxia changed the hemorheology and dry/wet weight ratio of lung of rats markedly. Metabolomics studies showed that the high altitude model group, high-dose SGTS group, low-dose SGTS group, and Hong-Jing-Tian capsule group can be obviously differentiated. Main markers such as 9-hexylheptadecane, glycine, N-methyl-N-methoxycarbonyl-ethyl ester, 2,4-Di-tert-butylphenol, were found to be the endogenous substances of SGTS which intervening the HAPC rats. It was concluded that SGTS can intervene low pressure and hypoxia induced HAPC.

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This study was aimed to find out the optimum parameters to decoction extraction process of Brassicae Radix cream . With methods of integrated score and uniform design , contents of the total extract and the total polysaccharide were set as the target to investigate the optimization process of extraction. The experiment showed that the optimum extraction condition was as follows: ten folds of water, four times decoction at boiling tempera-ture , one hour for each time . It was concluded that the optimum parameters to decoction extraction of Brassicae Radix were stable and feasible, which can be used for the preparation and reference for Brassicae Radix cream in Tibetan clinics .

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This study was aimed to establish the quality standard of Pyrethri Tatsienenis Flos. The medical material was identified by the microscopy and the thin layer chromatography ( TLC ) methods . The moisture , total ash , acid-insoluble ash and alcohol-soluble extract were determined according to procedures recorded in the Chi-nese Pharmacopoeia (2010 edition). The content of luteolin was determined by the HPLC method. The results showed a strong characteristic microscopic of Pyrethri Tatsienenis Flos , and its TLC identification had a good resolution with clear spots . The mass fractions of luteolin was 0 . 036%~0 . 104% ( average of 0 . 078%) , moisture was 9 . 32%~15 . 82% ( average of 13 . 11%) , total ash was 6 . 65%~8 . 29% ( average of 7 . 45%) , acid-insoluble ash was 0 . 23%~0 . 59% ( average of 0 . 42%) , and the extraction was 21 . 42%~30 . 15% ( average of 24 . 86%) . It was concluded that this established standard was simple to operate with good stability and reproducibility , which can be used for quality evaluation of Pyrethri Tatsienenis Flos .