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Advancements in genomic technologies have shown remarkable promise for improving health trajectories. The Human Genome Project has catalyzed the integration of genomic tools into clinical practice, such as disease risk assessment, prenatal testing and reproductive genomics, cancer diagnostics and prognostication, and therapeutic decision making. Despite the promise of genomic technologies, their full potential remains untapped without including individuals of diverse ancestries and integrating social determinants of health (SDOHs). The NHGRI launched the 2020 Strategic Vision with ten bold predictions by 2030, including "individuals from ancestrally diverse backgrounds will benefit equitably from advances in human genomics." Meeting this goal requires a holistic approach that brings together genomic advancements with careful consideration to healthcare access as well as SDOHs to ensure that translation of genetics research is inclusive, affordable, and accessible and ultimately narrows rather than widens health disparities. With this prediction in mind, this review delves into the two paramount applications of genetic testing-reproductive genomics and precision oncology. When discussing these applications of genomic advancements, we evaluate current accessibility limitations, highlight challenges in achieving representativeness, and propose paths forward to realize the ultimate goal of their equitable applications.
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Genómica , Medicina de Precisión , Humanos , Genómica/métodos , Medicina de Precisión/métodos , Genoma Humano , Pruebas Genéticas , Neoplasias/genética , Accesibilidad a los Servicios de SaludRESUMEN
Anemarrhena asphodeloides is a common medicinal material used in clinical prescriptions and Chinese patent medicine. In this study, the Illumina platform was used to obtain the chloroplast genome sequences of seven kinds of A. asphodeloides from different areas. The specific DNA barcodes were screened by comparative genomics analysis, and the DNA barcodes were used to identify the germplasm resources and analyze the genetic diversity of A. asphodeloides samples from different areas in China. All the seven chloroplast genomes had a ring structure. The total length was 156 801-156 930 bp, and 113 genes were annotated, including 79 protein-coding genes, 30 tRNA genes, and four rRNA genes. The comparative genomics analysis showed that rps16, trnG-GCC, atpF, rpoB, ycf3, rpl16, ndhF, trnS-GCU_trnG-GCC, petN-psbM, and ndhF-rpl32 were potential candidates for specific DNA barcodes of A. asphodeloides. In this study, the second intron of ycf3 and atpF intron sequences with a sequence length of 700-800 bp and easy amplification were selected for polymerase chain reaction(PCR) amplification and sequencing of 594 samples from 26 areas. The sequence analysis showed that six and eight haplotypes of ycf3 and atpF sequences could be identified, respectively, and 17 haplotypes could be identified by combined analysis of the two sequences, which were named Hap1-Hap17. The haplotype diversity(H_d), nucleotide diversity(P_i), and genetic distance of A. asphodeloides in 26 populations were 0.68, 0.93×10~(-3), and 0-0.003 1, respectively, indicating that the genetic diversity within the species of A. asphodeloides is rich. The intermediary adjacent network analysis showed that Hap5 was the oldest haplotype, which was mainly distributed in Yixian county of Baoding, Hebei province, Hequ county of Xinzhou, Shanxi province, and Xiangfen county of Linfen, Shanxi province. This study has important guiding significance for the identification of A. asphodeloides species, the protection and development of germplasm resources, and the identification of production areas, and it provides a research basis for further revealing the genetic evolution law of A. asphodeloides.
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Anemarrhena , Anemarrhena/química , Código de Barras del ADN Taxonómico , Variación Genética , China , FilogeniaRESUMEN
Shengjiang Xiexin decoction (SXD), a well-known traditional Chinese medicine (TCM), was used to alleviate delayed-onset diarrhea induced by the chemotherapeutic agent irinotecan (CPT-11). Our previous study showed that SXD regulated multidrug resistance-associated protein 2 (Mrp-2) to alter the pharmacokinetics of CPT-11 and its metabolites. However, the pharmacodynamic constituents and the related quality markers of SXD are unclear. In this study, ultra-high performance liquid chromatography coupled with quadrupole orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) was utilized to identify the prototypes and metabolites in rat plasma after oral administration of SXD. The pharmacokinetic markers (PK markers) were screened through quantification and semiquantification of SXD-related xenobiotics in plasma using liquid chromatography-mass spectrometry (LC-MS) combined with statistical analysis. Computational molecular docking was performed to assess the potential binding ability of the PK markers with the target Mrp-2. The results were verified by evaluating the impact on Mrp-2 function using Caco-2 cells. The quality markers were chosen from these PK markers based on the binding affinities with Mrp-2, the specificity and the traceability. As a result, a total of 142 SXD-related exogenous components, including 77 prototypes and 65 metabolites, were detected in rat plasma. Among these, 83 xenobiotics were selected as PK markers due to their satisfactory pharmacokinetic behaviors. Based on the characteristics of quality markers, the prototype-based PK markers were considered the indices of quality control for SXD, including baicalin, baicalein, wogonoside, wogonin, liquiritigenin, isoliquiritigenin, norwogonin, oroxylin A, dihydrobaicalin, chrysin, glycyrrhizic acid, glycyrrhetinic acid, oroxylin A 7-O-glucuronide, liquiritin and isoliquiritin. This study provided an interesting strategy for screening the quality markers involved in the pharmacokinetics of SXD and its action target, which offered important information for the modernization of SXD and other TCM formulae.
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Medicamentos Herbarios Chinos , Humanos , Ratas , Animales , Ratas Sprague-Dawley , Irinotecán , Células CACO-2 , Simulación del Acoplamiento Molecular , Medicamentos Herbarios Chinos/química , Cromatografía Líquida de Alta Presión/métodosRESUMEN
Rationale: Vitamin D (VD) has been suggested to have antitumor effects, however, research on the role of its transporter vitamin D-binding protein (VDBP, gene name as GC) in tumors is limited. In this study, we demonstrated the mechanism underlying the inhibition of vasculogenic mimicry (VM) by VDBP in hepatocellular carcinoma (HCC) and proposed an anti-tumor strategy of combining anti-PD-1 therapy with VD. Methods: Three-dimensional cell culture models and mice with hepatocyte-specific GC deletion were utilized to study the correlation between VDBP expression and VM. A patient-derived tumor xenograft (PDX) model was further applied to validate the therapeutic efficacy of VD in combination with an anti-PD-1 drug. Results: The study revealed that VDBP expression is negatively correlated with VM in HCC patients and elevated VDBP expression is associated with a favorable prognosis. The mechanism studies suggested VDBP hindered the binding of Twist1 on the promoter of VE-cadherin by interacting with its helix-loop-helix DNA binding domain, ultimately leading to the inhibition of VM. Furthermore, VD facilitated the translocation of the vitamin D receptor (VDR) into the nucleus where VDR interacts with Yin Yang 1 (YY1), leading to the transcriptional activation of VDBP. We further demonstrated that the combination of VD and anti-PD-1 led to an improvement in the anti-tumor efficacy of an anti-PD-1 drug. Conclusion: Collectively, we identified VDBP as an important prognostic biomarker in HCC patients and uncovered it as a therapeutic target for enhancing the efficacy of immune therapy.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Ratones , Animales , Carcinoma Hepatocelular/patología , Proteína de Unión a Vitamina D/uso terapéutico , Neoplasias Hepáticas/patología , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/metabolismo , Diferenciación Celular , Línea Celular TumoralRESUMEN
BACKGROUND: With the increasing prevalence of hypertension, diabetes, and obesity, the incidence of kidney diseases is also increasing, resulting in a serious public burden. Conventional treatments for kidney diseases have unsatisfactory effects and are associated with adverse reactions. Traditional Chinese medicines have good curative effects and advantages over conventional treatments for preventing and treating kidney diseases. Astragali Radix is a Chinese herbal medicine widely used to treat kidney diseases. PURPOSE: To review the potential applications and molecular mechanisms underlying the renal protective effects of Astragali Radix and its components and to provide direction and reference for new therapeutic strategies and future research and development of Astragali Radix. STUDY DESIGN AND METHODS: PubMed, Google Scholar, and Web of Science were searched using keywords, including "Astragali Radix," "Astragalus," "Astragaloside IV" (AS-IV), "Astragali Radix polysaccharide" (APS), and "kidney diseases." Reports on the effects of Astragali Radix and its components on kidney diseases were identified and reviewed. RESULTS: The main components of Astragali Radix with kidney-protective properties include AS-IV, APS, calycosin, formononetin, and hederagenin. Astragali Radix and its active components have potential pharmacological effects for the treatment of kidney diseases, including acute kidney injury, diabetic nephropathy, hypertensive renal damage, chronic glomerulonephritis, and kidney stones. The pharmacological effects of Astragali Radix are manifested through the inhibition of inflammation, oxidative stress, fibrosis, endoplasmic reticulum stress, apoptosis, and ferroptosis, as well as the regulation of autophagy. CONCLUSION: Astragali Radix is a promising drug candidate for treating kidney diseases. However, current research is limited to animal and cell studies, underscoring the need for further verifications using high-quality clinical data.
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Planta del Astrágalo , Medicamentos Herbarios Chinos , Enfermedades Renales , Saponinas , Triterpenos , Animales , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Medicina Tradicional China , Raíces de Plantas , Inflamación , Enfermedades Renales/tratamiento farmacológicoRESUMEN
The aim of this study was to investigate the changes in human and animal milk oligosaccharides over lactation. In total, 89, 97, 115, and 71 oligosaccharides were identified in human, bovine, goat, and camel milk. The number of common oligosaccharides between camel and human milk was the highest (16 and 17 in transitional and mature milk). With respect to the absolute concentration of eight oligosaccharides (2'-FL, 3-FL, α3'-GL, LNT, LNnT, 3'-SL, 6'-SL, and DSL), 2'-FL, 3'-FL, LNT, and LNnT were much higher in human than three animal species. 3'-SL had a similar concentration in bovine colostrum (322.2 µg/mL) and human colostrum (321.0 µg/mL), followed by goat colostrum (105.1 µg/mL); however, it had the highest concentration in camel mature milk (304.5 µg/mL). The ratio of 6'-SL and 3'-SL (1.77) in goat colostrum was similar to that in human colostrum (1.68), followed by bovine colostrum (0.13). In terms of changes of eight oligosaccharides over lactation, they all decreased with the increase of lactation in bovine and goat milk; however, α3'-GL, 2'-FL, and 3-FL increased in camel species, and LNT increased first and then decreased over lactation in human milk. This study provides a better understanding of the variation of milk oligosaccharides related to lactation and species.
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Camelus , Leche , Humanos , Embarazo , Femenino , Bovinos , Animales , Lactancia , Calostro , Leche Humana , Cabras , OligosacáridosRESUMEN
BACKGROUND: Myocardial ischemia/reperfusion injury (MI/RI) is involved in a variety of pathological states for which there is no effective treatment exists. Shuangshen Ningxin (SSNX) capsule which is developed by Xiyuan Hospital, Chinese Academy of Traditional Chinese Medicine has been demonstrated to alleviate MI/RI, but its mechanism remains to be further elucidated. METHODS: The MI/RI miniature pigs model was constructed to assess the pharmacodynamics of SSNX by blocking the proximal blood flow of the left anterior descending branch of the cardiac coronary artery through an interventional balloon. The principal chemical compounds and potential targets of SSNX were screened by HPLC-MS and SwissTargetPrediction. The targets of MI/RI were identified based on Online Mendelian Inheritance in Man (OMIM) and GeneCards. Cytoscape 3.9.0 was applied to construct a protein-protein interaction (PPI) network, and Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using metascape. To further validate the mechanism of SSNX, Molecular docking, Transmission electron microscopy, and Western blot analysis were used to test the effectiveness of targets in related pathways. RESULTS: Our results indicated that SSNX significantly improved cardiac function, attenuated myocardial I/R injury. Through network analysis, a total of 15 active components and 201 targets were obtained from SSNX, 75 of which are potential targets for the treatment of MI/RI. KEGG and MCODE analysis showed that SSNX is involved in the mitophagy signaling pathway, and ginsenoside Rg1, ginsenoside Rb1 and ginsenoside Rb2 are key components associated with the mitophagy. Further experimental results proved that SSNX protected mitochondrial structure and function, and significantly reduced the expression of mitophagy-related proteins PTEN-induced putative kinase 1 (PINK1), Parkin, FUN14 domain containing 1 (FUNDC1) and Bcl-2/E1B-19 kDa interacting protein 3 (BNIP3) in MI/RI miniature pigs. CONCLUSION: In our study, the integration of network pharmacology and experiments in vivo demonstrated that SSNX interfered with MI/RI by inhibiting mitophagy.
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Chronic respiratory diseases (CRD), is a group of disorders, primarily chronic obstructive pulmonary disease and asthma, which are characterized by high prevalence and disability, recurrent acute exacerbations, and multiple comorbidities, resulting in exercise limitations and reduced health-related quality of life. Exercise training, an important tool in pulmonary rehabilitation, reduces adverse symptoms in patients by relieving respiratory limitations, increasing gas exchange, increasing central and peripheral hemodynamic forces, and enhancing skeletal muscle function. Aerobic, resistance, and high-intensity intermittent exercises, and other emerging forms such as aquatic exercise and Tai Chi effectively improve exercise capacity, physical fitness, and pulmonary function in patients with CRD. The underlying mechanisms include enhancement of the body's immune response, better control of the inflammatory response, and acceleration of the interaction between the vagus and sympathetic nerves to improve gas exchange. Here, we reviewed the new evidence of benefits and mechanisms of exercise intervention in the pulmonary rehabilitation of patients with chronic obstructive pulmonary disease, bronchial asthma, bronchiectasis, interstitial lung disease, and lung cancer.
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Asma , Enfermedad Pulmonar Obstructiva Crónica , Trastornos Respiratorios , Humanos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/terapia , Calidad de Vida , Pulmón , Terapia por Ejercicio , Asma/diagnóstico , Asma/terapia , Tolerancia al EjercicioRESUMEN
BACKGROUND: Immunoglobulin A nephropathy (IgAN), is the main cause of end-stage renal disease, that causes serious physical and psychological burden to patients worldwide. Some traditional treatment measures, such as blocking the renin-angiotensin-aldosterone system, controlling blood pressure, and following a low-protein diet, may not achieve satisfactory results. Therefore, more effective and safe therapies for IgAN are urgently needed. PURPOSE: The aim of this review is to summarize the clinical efficacy of Chinese herbal medicines (CHMs) and their active ingredients in the treatment and management of IgAN based on the results of clinical trials, systematic reviews, and meta-analyses, to fully understand the advantages and perspectives of CHMs in the treatment of IgAN. STUDY DESIGN AND METHODS: For this review, the following electronic databases were consulted: PubMed, ResearchGate, Science Direct, Web of Science, Chinese National Knowledge Infrastructure and Wanfang Data, "IgA nephropathy," "traditional Chinese medicine," "Chinese herbal medicine," "herb," "mechanism," "Meta-analysis," "systematic review," "RCT" and their combinations were the keywords to search the relevant literature. Data were collected from 1990 to 2022. RESULTS: This review found that the active ingredients of CHMs commonly act on multiple signaling pathways in the clinical treatment of IgAN, mainly with antioxidant, anti-inflammatory and anti-fibrosis effects, and regulation of autophagy. CONCLUSION: Compared with the single-target therapy of modern medicine, CHMs can regulate the corresponding pathways from the aspects of anti-inflammation, anti-oxidation, anti-fibrosis and autophagy to play a multi-target treatment of IgAN through syndrome differentiation and treatment, which has good clinical efficacy and can be used as the first choice or alternative therapy for IgAN treatment. This review provides evidence and research direction for a comprehensive clinical understanding of the protective effect of Chinese herbal medicine on IgAN.
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Medicamentos Herbarios Chinos , Glomerulonefritis por IGA , Humanos , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Glomerulonefritis por IGA/tratamiento farmacológico , Glomerulonefritis por IGA/inducido químicamente , Medicina Tradicional China/métodos , Resultado del TratamientoRESUMEN
Acute kidney injury (AKI) is a major health concern owing to its high morbidity and mortality rates, to which there are no drugs or treatment methods, except for renal replacement therapy. Therefore, identifying novel therapeutic targets and drugs for treating AKI is urgent. Ferroptosis is an iron-dependent and lipid-peroxidation-driven regulatory form of cell death and is closely associated with the occurrence and development of AKI. Traditional Chinese medicine (TCM) has unique advantages in treating AKI due to its natural origin and efficacy. In this review, we summarize the mechanisms underlying ferroptosis and its role in AKI, and TCM compounds that play essential roles in the prevention and treatment of AKI by inhibiting ferroptosis. This review suggests ferroptosis as a potential therapeutic target for AKI, and that TCM compounds show broad prospects in the treatment of AKI by targeting ferroptosis.
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Lesión Renal Aguda , Ferroptosis , Humanos , Medicina Tradicional China , Lesión Renal Aguda/tratamiento farmacológico , Muerte Celular , HierroRESUMEN
Eleutherococcus senticosus is one of the Dao-di herbs in northeast China. In this study, the chloroplast genomes of three E. senticosus samples from different genuine producing areas were sequenced and then used for the screening of specific DNA barcodes. The germplasm resources and genetic diversity of E. senticosus were analyzed basing on the specific DNA barcodes. The chloroplast genomes of E. senticosus from different genuine producing areas showed the total length of 156 779-156 781 bp and a typical tetrad structure. Each of the chloroplast genomes carried 132 genes, including 87 protein-coding genes, 37 tRNAs, and 8 rRNAs. The chloroplast genomes were relatively conserved. Sequence analysis of the three chloroplast genomes indicated that atpI, ndhA, ycf1, atpB-rbcL, ndhF-rpl32, petA-psbJ, psbM-psbD, and rps16-psbK can be used as specific DNA barcodes of E. senticosus. In this study, we selected atpI and atpB-rbcL which were 700-800 bp and easy to be amplified for the identification of 184 E. senticosus samples from 13 genuine producing areas. The results demonstrated that 9 and 10 genotypes were identified based on atpI and atpB-rbcL sequences, respectively. Furthermore, the two barcodes identified 23 genotypes which were named H1-H23. The haplotype with the highest proportion and widest distribution was H10, followed by H2. The haplotype diversity and nucleotide diversity were 0.94 and 1.82×10~(-3), respectively, suggesting the high genetic diversity of E. senticosus. The results of the median-joining network analysis showed that the 23 genotypes could be classified into 4 categories. H2 was the oldest haplotype, and it served as the center of the network characterized by starlike radiation, which suggested that population expansion of E. senticosus occurred in the genuine producing areas. This study lays a foundation for the research on the genetic quality and chloroplast genetic engineering of E. senticosus and further research on the genetic mechanism of its population, providing new ideas for studying the genetic evolution of E. senticosus.
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Código de Barras del ADN Taxonómico , Eleutherococcus , Eleutherococcus/genética , Secuencia de Bases , Cloroplastos/genética , Variación Genética , FilogeniaRESUMEN
Results: EA intervention and OxPAPC injection could relieve mechanical allodynia and thermal hyperalgesia caused by CIA. Paw edema and pathological damage of synovium were significantly ameliorated after EA intervention and OxPAPC injection. Furthermore, EA intervention and OxPAPC injection markedly reduced the contents of serum TNF-α, IL-1ß, and IL-6, as well as the protein expression levels of synovial TLR2, TLR4, MyD88, and NF-κB p-p65. In particular, the expression of TLR2 and TLR4 on synovial fibroblasts and macrophages in synovium was significantly reduced by EA intervention. Conclusions: Repeated EA stimulation at ST36 and SP6 can effectively relieve joint pain and synovial inflammation caused by RA in CIA rats. The analgesic and anti-inflammatory effect of EA may be closely related to the inhibition of innate immune responses driven by the TLR2/4-MyD88-NF-κB signaling pathway in the synovium.
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Context: Since December 2019, medical practitioners discovered a novel coronavirus causing an acute respiratory-tract infection in some hospitals in Wuhan, Hubei Province. COVID-19 has spread globally, making it an epidemic worldwide at present. Understanding the mental-health responses of college students to COVID-19 can help a school staff to better guide students seeking education. Objective: The study aimed to explore the differences between nonmedical and medical college students during the COVID-19 epidemic in their cognitive interest about the disease, preventive behaviors, psychological effects, and job-search intentions, hoping to provide more targeted measures for virus-coping education for college students. Design: The research team conducted a cross-sectional study, using an anonymous online questionnaire. Setting: The study took place at Shanghai, China. Participants: Participants were 1648 college students studying different specialties in various provinces of China, 485 nonmedical students and 1163 medical students. Outcome Measures: The survey's questions covered the respondents': (1) general demographic characteristics, (2) cognitive interest and knowledge about COVID-19 and its infectiousness as well as efforts at active learning about infectious diseases and viruses, (3) awareness of precautionary behaviors against COVID-19, (4) effects on mental health, and (5) effects on job-search intentions. The research team used descriptive statistics and Chi-square tests to analyze the survey data. Results: Among nonmedical students: (1) 297 participants (61.2%) were interested in learning about COVID-19, (2) 321 participants (66.2%) took the initiative to learn about the virus, (3) 301 participants (62.1%) took the initiative to learn about infectious disease, and (4) 151 participants (31.1%) watched medical-themed movies or TV series about COVID-19. Among medical students, the corresponding proportions were 772 participants (66.4%), 855 participants (73.5%), 791 participants (68.1%), and 791 participants (68.1%), respectively. Among nonmedical students, 223 participants (46.0%) had N95 masks available, 429 participants (88.5%) had disinfectant supplies available, 271 participants (55.9%) wore goggles in public places, 75 participants (15.5%) chose public transportation, and 77 participants (15.9%) were exposed to public places in the week prior to the survey. Among medical students, the corresponding proportions were 470 participants (40.4%), 935 participants (80.4%), 575 participants (49.4%), 243 participants (20.9%), and 297 participants (25.5%), respectively. Furthermore, COVID-19 had a stronger effect on medical students' psychology and job-search ambitions. Conclusions: The news about COVID-19 piqued the interest of medical students. Nonmedical students had stronger protective behavior than medical students. The COVID-19 outbreak had a significant influence on medical students' lives, studies, and moods. In addition, COVID-19 had a greater impact on the job-search intentions of medical students.
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COVID-19 , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Intención , Estudios Transversales , China/epidemiología , Estudiantes/psicología , Cognición , Encuestas y CuestionariosRESUMEN
Preharvest shading significantly influences tea flavor. However, little attention has been given to the mechanism of shading on metabolites, genes, and enzymes in the processing of different tea types. Our study identified 1028 nonvolatile metabolites covering 10 subclasses using a widely targeted metabolome. The results show that shading had a greater effect on the compositions of amino acids, flavonoids, and theaflavins in tea leaves. The combined transcriptomics and enzyme activity analysis results indicate that the upregulated expression of asparagine, aspartate, and tryptophan synthesis genes and proteolytic enzymes promoted the accumulation of amino acids. The downregulated enzyme genes resulted in the reduction of nongalloylated catechins and flavonoid glycosides. Simultaneously, the accumulation of TFs in shaded tea was due to the enhanced enzymatic activities of polyphenol oxidase and peroxidase during processing. Theaflavin-3-3'-di-O-gallate was also significantly positively correlated with the antioxidant and hypoglycemic activities of shaded tea. The results contribute to a better understanding of how preharvest treatments influence summer tea quality.
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Camellia sinensis , Catequina , Camellia sinensis/química , Té/química , Catequina/metabolismo , Flavonoides/metabolismo , Transcriptoma , Aminoácidos/metabolismo , Hojas de la Planta/químicaRESUMEN
Glomerular diseases are major components of kidney disease, mainly manifested as podocyte disease, immune complex-associated glomerulonephritis, and renal autoimmune disease. They are the third leading cause of end-stage renal disease, especially in younger populations. Podocyte death or shedding is a key factor in the progression of glomerular diseases, and autophagy plays an important role in maintaining podocyte homeostasis. Dysfunction of autophagy has been associated with the progression of various glomerular diseases. Modulation of autophagy has been shown to play a protective role in experimental models of glomerular diseases, suggesting that autophagy is a potential therapeutic target for glomerular diseases. Traditional Chinese medicine (TCM) has unique advantages in the treatment of kidney disease. In vivo and in vitro studies have shown that TCM compounds can reduce podocyte apoptosis, inhibit inflammation, improve endoplasmic reticulum stress and oxidative stress responses, and play an active role via autophagy. This review summarizes the roles of autophagy in glomerular diseases and provides evidence that TCM compounds can regulate autophagy through different signaling pathways to ameliorate glomerular diseases.
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Glomerulonefritis , Enfermedades Renales , Podocitos , Humanos , Medicina Tradicional China , Enfermedades Renales/tratamiento farmacológico , Autofagia , Riñón , Glomerulonefritis/tratamiento farmacológicoRESUMEN
Recently, with increasing awareness of health issues, non-alcoholic fatty liver disease (NAFLD) has become an epidemic attracting global attention. As a serious chronic disease, NAFLD is clinically managed with pharmacological interventions that are usually associated with poor long-term efficacy and adverse effects. In this scenario, traditional Chinese medicine (TCM) characterized by "multiple ingredients-multiple targets-multiple pathways" shows promise as a potential option to treat NAFLD. Zexie decoction (ZXD) is a classical TCM formula that possesses favorable lipid-lowering and anti-inflammatory activities. Accumulating evidence indicates that ZXD displays robust efficacy in treating NAFLD. The effectiveness of ZXD against NAFLD has been evaluated in our previous studies. This study further examines its probable mechanism of action in an in-depth manner using multi-omic analysis based on the gut-liver axis and sheds light on the potential relationship among genes, hepatic lipid metabolites, and gut microbiotas. Totally, 71 differentially expressed genes (34 upregulated and 37 downregulated genes), 31 differential lipid molecules (8 upregulated and 23 downregulated), and 56 differential gut microbiotas (37 upregulated and 19 downregulated) were identified in the ZXD-treated group rats compared with the negative control group rats. Of these, owing to their key role in the association analysis, g_Blautia, g_Romboutsia, and g_Lactobacillus were hypothesized to be crucial gut microbiotas in the ZXD-mediated treatment of NAFLD. These microbiotas were found to synergize with key genes, such as AKR1B8, CCN1, and TNKS2, and hepatic lipid metabolites, such as glycerophospholipid and sphingomyelin, which might play a therapeutic role by regulating fatty acid synthesis, correcting lipid metabolism disorder, or reducing the inflammatory response. Overall, the present study provides fresh insights into the ZXD-mediated treatment of NAFLD, which, in turn, is expected to give a push to the modernization of TCM.
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Microbioma Gastrointestinal , Enfermedad del Hígado Graso no Alcohólico , Ratas , Animales , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Esfingomielinas/metabolismo , Hígado/metabolismo , Ácidos Grasos/metabolismo , Glicerofosfolípidos/metabolismo , Glicerofosfolípidos/farmacología , Glicerofosfolípidos/uso terapéutico , Dieta Alta en Grasa/efectos adversosRESUMEN
Children/adolescents with type 1 diabetes (T1D) require holistic approach and continuous care. However, the coronavirus disease 2019 (COVID-19) pandemic has made challenges for the T1D children and their caregivers, professionals, and the healthcare system. This minireview aims to consolidate and discuss the difficulties and solutions of children with type 1 diabetes in the COVID-19 pandemic. T1D has been the most common type of diabetes in children and adolescents and the last decades has seen a rapid increase in the prevalence of T1D in youths worldwide, which deserves a public concern particularly in the COVID-19 pandemic. As reported in previous studies, T1D is a risk factor related to severe cases, while the virus may induce new-onset diabetes and serious complications. Moreover, restriction strategies influence medical availability and lifestyle, impact glycemic control and compilation management, and thus pose stress on families and health providers of youths with T1D, especially on those with certain fragile conditions. Therefore, special treatment plans are required for children provided by caregivers and the local health system. Latest health tools such as improved medical devices and telemedicine service, as well as a combined support may benefit in this period. This minireview emphasises that continued medical access and support are required to prevent deteriorated condition of children and adolescents with diabetes throughout this pandemic. Therefore, strategies are supposed to be formulated to mitigate the difficulties and stress among this group, particularly in the most at-risk population. Proposed solutions in this minireview may help individuals and the health system to overcome these problems and help youths with T1D in better diabetes management during such emergency situations.
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Background: Birthweight have profound impacts on health status throughout lifetime, however, the relationship between maternal ferritin level in pregnancy and birthweight of the newborn remains controversial. Objective: This retrospective cohort research was to analyze the association between maternal ferritin levels during pregnancy with birthweight outcomes, primarily for low birthweight (LBW) and small for gestational age (SGA). Methods: Newborns weighing lower than 2,500 grams were defined as LBW. SGA is defined as birthweight lower than the 10th percentile of the distribution of newborns' birthweight of the same gestational age. Multivariable logistic regressions have been used to explore the association of maternal ferritin levels and birthweight related outcomes, in which the ferritin concentration was logarithm transformed in the model. We further used restricted cubic spline models to explore linear/non-linear dose-response manners of ferritin level and birthweight outcomes. Results: A total of 3,566 pregnant women were included in the study. In the results of the present study, we observed that maternal ferritin levels were linearly associated with the risk of LBW (p-trend = 0.005) and SGA (p-trend = 0.04), with the adjusted odds ratios (ORs) of 1.78 (95% CI 1.37-2.32) for LBW and 1.87 (95% CI 1.38-2.54) for SGA with an increase in Ln-ferritin concentrations per unit. The adjusted ORs across quartiles of ferritin levels were 2.14 (95% CI 1.03-4.47) for Quartile 2, 3.13 (95% CI 1.47-6.69) for Quartile 3, and 3.63 (95% CI 1.52-8.68) for Quartile 4 for LBW. The adjusted ORs of LBW and SGA among women using supplemental iron were 0.56 (95% CI 0.38, 0.85) and 0.65 (95% CI 0.40, 1.05) compared with non-users, respectively. Conclusions: Our findings found a linear dose-response relationship between ferritin levels and an increased risk of poor birthweight outcomes, suggesting that maternal ferritin level during pregnancy may provide an additional predictor for differentiating poor birthweight related outcomes. Further exploration should be conducted to ensure maternal ferritin thresholds and iron supplement doses.
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Background: Glucocorticoid-induced osteoporosis (GIOP) is a common form of secondary osteoporosis caused by the protracted or a large dosage of glucocorticoids (GCs). Total flavonoids of Drynariae rhizoma (TFDR) have been widely used in treating postmenopausal osteoporosis (POP). However, their therapeutic effects and potential mechanism against GIOP have not been fully elucidated. Methods: Ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESIQ-TOF-MS) experiments were performed for qualitative analysis. We performed hematoxylin-eosin (HE) staining and microcomputed tomography (micro-CT) analysis to detect the changes in bone microstructure. The changes in biochemical parameters in the serum samples were determined by performing an enzyme-linked immunosorbent assay (ELISA). The prediction results of network pharmacology were verified via quantitative real-time polymerase chain reaction (qRT-PCR) to elucidate the potential mechanism of TFDR against GIOP. Results: A total of 191 ingredients were identified in vitro and 48 ingredients in vivo. In the in-vivo experiment, the levels of the serum total cholesterol (TC), the serum triglyceride (TG), Leptin (LEP), osteocalcin (OC), osteoprotegerin (OPG), bone morphogenetic protein-2 (BMP-2), propeptide of type I procollagen (PINP), tartrate-resistant acid phosphatase (TRACP) and type-I collagen carboxy-terminal peptide (CTX-1) in the TFDR group significantly changed compared with those in the GIOP group. Moreover, the TFDR group showed an improvement in bone mineral density and bone microstructure. Based on the results of network pharmacology analysis, 67 core targets were selected to construct the network and perform PPI analysis as well as biological enrichment analysis. Five of the targets with high "degree value" had differential gene expression between groups using qRT-PCR. Conclusion: TFDR, which may play a crucial role between adipose metabolism and bone metabolism, may be a novel remedy for the prevention and clinical treatment of GIOP.
Asunto(s)
Osteoporosis , Polypodiaceae , Animales , Cromatografía Líquida de Alta Presión , Flavonoides/farmacología , Glucocorticoides/efectos adversos , Farmacología en Red , Osteoporosis/inducido químicamente , Osteoporosis/tratamiento farmacológico , Osteoporosis/metabolismo , Polypodiaceae/química , Ratas , Microtomografía por Rayos XRESUMEN
Shengjiang Xiexin decoction, a traditional Chinese medical formula, has been utilized to alleviate the delayed-onset diarrhea induced by irino tecan. However, the chemical constituents of this formula and the activities of its constituents remain unclear. In this study, ultrahigh-performance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry was employed to comprehensively analyze the chemical constituents of Shengjiang Xiexin decoction. A total of 270 components, including flavonoids, coumarins, triterpenoids, alkaloids, diarylheptanoids and others, were identified or characterized. Multidrug resistance-associated protein 2 is an efflux transporter responsible for regulating drug absorption. A total of 20 characteristic components from the formula were selected to evaluate their effects on the function of multidrug resistance-associated protein 2 using the vesicular transport assay. Glycyrrhizic acid and glycyrrhetinic acid were identified as potential multidrug resistance-associated protein 2 inhibitors, while 9 flavonoid aglycones increased the uptake of the substrate [3 H]-estradiol 17-ß-glucuronide in the vesicles. This was the first systematic investigation of the chemical constituents from Shengjiang Xiexin decoction and the effect of its characteristic components on the transporter. The results offered a basis for further exploring the detoxification mechanisms of this formula and its interactions with other drugs.