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Herb compatibility is the soul of traditional Chinese Medicine prescriptions. Coptidis rhizoma (CR) (Coptis chinensis Franch., Coptis deltoidea C.Y.Cheng et Hsiao, or Coptis teeta Wall.; family Ranunculaceae), is a well-known herb. The bitter and cold nature of CR can irritate the spleen and stomach, and certain ingredients in CR may trigger allergic reactions. Herb combinations can help alleviate the side effects caused by CR. Through data analysis and literature research, there are many herbs combined with CR have a high frequency, but only a few are currently used as formulae in clinical practice. The results showed that these six herb pairs are usually widely studied or used as prescriptions in the clinic. This paper describes the six herb pairs from the key traditional uses, changes in bioactive constituents, and compatibility effects, especially with Euodiae fructus (family Rutaceae), Scutellariae radix (family Lamiaceae), Magnoliae Officinalis cortex (family Magnoliaceae), Glycyrrhizae radix et rhizoma (family Fabaceae), Ginseng radix et rhizoma (family Araliaceae), and Aucklandiae radix (family Asteraceae), and found that herbs are more effective when used in combination. Therefore, it is feasible to establish some methods to study herb pairs comprehensively from different perspectives. This paper aims to provide the latest and most comprehensive information on the six herb pairs and summarize the pattern of CR compatibility effects. It aims to attract more attention, and further experimental studies will be conducted to investigate and evaluate the effects of herb pairs containing CR. These data can also provide valuable references for researchers and also provide more possibilities for future applications in clinical practice and new drug development.
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BACKGROUND: An increasing number of studies have focused on the role of cellular metabolism in the development of colorectal cancer (CRC). However, no work is currently available to synthesize the field through bibliometrics. AIM: To analyze the development in the field of "glucose metabolism" (GM), "amino acid metabolism" (AM), "lipid metabolism" (LM), and "nucleotide metabolism" (NM) in CRC by visualization. METHODS: Articles within the abovementioned areas of GM, AM, LM and NM in CRC, which were published from January 1, 1991, to December 31, 2022, are retrieved from the Web of Science Core Collection and analyzed by CiteSpace 6.2.R4 and VOSviewer 1.6.19. RESULTS: The field of LM in CRC presented the largest number of annual publications and the fastest increase in the last decade compared with the other three fields. Meanwhile, China and the United States were two of the most prominent contributors in these four areas. In addition, Gang Wang, Wei Jia, Maria Notarnicola, and Cornelia Ulrich ranked first in publication numbers, while Jing-Yuan Fang, Senji Hirasawa, Wei Jia, and Charles Fuchs were the most cited authors on average in these four fields, respectively. "Gut microbiota" and "epithelial-mesenchymal transition" emerged as the newest burst words in GM, "gut microbiota" was the latest outburst word in AM, "metastasis", "tumor microenvironment", "fatty acid metabolism", and "metabolic reprogramming" were the up-to-date outbreaking words in LM, while "epithelial-mesenchymal transition" and "apoptosis" were the most recently occurring words in NM. CONCLUSION: Research in "cellular metabolism in CRC" is all the rage at the moment, and researchers are particularly interested in exploring the mechanism to explain the metabolic alterations in CRC. Targeting metabolic vulnerability appears to be a promising direction in CRC therapy.
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A simple and efficient visible-light-promoted selenylation/cyclization of o-alkynyl benzylazides/o-propargyl arylazides have been realized for the practical synthesis of seleno-substituted isoquinolines and quinolines. This strategy provides the synthesis of valuable seleno-substituted isoquinoline and quinoline derivatives via the construction of one C(sp2)-Se bond and one C-N bond within one process.
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AIM: To compare the consistency of two autorefractors (Tianle RM-9000 and Topcon KR-800) for school-age myopia children, and to provide a basis for largescale data analysis and comparison. METHODS: The refractive error in 909 subjects (age 4-18y) were measured using both autorefractors without cycloplegia. The data were analyzed using Fourier decomposition and the correlation coefficients, intraclass correlation coefficients (ICC), and Bland-Altman limits of agreement (LoA) for each parameter were calculated. RESULTS: There was a strong correlation between the spherical equivalent (SE), sphere diopter (DS), and cylinder diopter (DC) readings of the Tianle RM-9000 and those of the Topcon KR-800, with correlation coefficient values of 0.98, 0.98 and 0.83 and ICC values of 0.99, 0.99 and 0.93, respectively. However, the correlation coefficients and ICC values of J0 and J45 were unreliable (R=-0.004, -0.034; both ICC<0.10). Bland-Altman analysis revealed that SE, DS, and DC measured by the Tianle RM-9000 were significantly biased toward myopia compared with the Topcon KR-800, and the mean differences were -0.072, -0.026, -0.091 D, respectively (all P<0.01). The minimum absolute value of the difference within the 95% LoA for SE, DS, and DC was 0.63 D, 0.50 D, 0.62 D, respectively; all these values were in the clinically acceptable range. For J0 and J45, the mean differences were close to zero (P=0.43, 0.84); however, the 95% LoA were relatively wide (J0 SD: 0.53; 95%CI: -1.00, 1.10; J45 SD: 0.52; 95%CI: -1.00, 1.00). CONCLUSION: The two autorefractors are consistent with each other, as the differences in SE, DS, and DC were within the clinically acceptable range. Readers can compare the data measured by either device in different studies and use the two devices in the same study to generate a dataset that can be analyzed together. However, the J0 and J45 vectors are unreliable and should not be used to assess astigmatism.
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AIM: To assess glaucoma patient satisfaction and follow-up adherence in case management and identify associated predictors to improve healthcare quality and patient outcomes. METHODS: In this cross-sectional study, a total of 119 patients completed a Patient Satisfaction Questionnaire-18 and a sociodemographic questionnaire. Clinical data was obtained from the case management system. Follow-up adherence was defined as completing each follow-up within ±30d of the scheduled time set by ophthalmologists during the study period. RESULTS: Average satisfaction scored 78.65±7, with an average of 4.39±0.58 across the seven dimensions. Age negatively correlated with satisfaction (P=0.008), whilst patients with follow-up duration of 2 or more years reported higher satisfaction (P=0.045). Multivariate logistics regression analysis revealed that longer follow-up durations were associated with lower follow-up adherence (OR=0.97, 95%CI, 0.95-1.00, P=0.044). Additionally, patients with suspected glaucoma (OR=2.72, 95%CI, 1.03-7.20, P=0.044) and those with an annual income over 100 000 Chinese yuan demonstrated higher adherence (OR=5.57, 95%CI, 1.00-30.89, P=0.049). CONCLUSION: The case management model proves effective for glaucoma patients, with positive adherence rates. The implementation of this model can be optimized in the future based on the identified factors and extended to glaucoma patients in more hospitals.
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The microecological stability of the gut microbiota plays a pivotal role in both preventing and treating colorectal cancer (CRC). This study investigated whether Lactobacillus plantarum CBT (LP-CBT) prevents CRC by inducing alterations in the gut microbiota composition and associated metabolites. The results showed that LP-CBT inhibited colorectal tumorigenesis in azoxymethane/dextran sulfate sodium (AOM/DSS)-treated mice by repairing the intestinal barrier function. Furthermore, LP-CBT decreased pro-inflammatory cytokines and anti-inflammatory cytokines. Importantly, LP-CBT remodeled intestinal homeostasis by increasing probiotics (Coprococcus, Mucispirillum, and Lactobacillus) and reducing harmful bacteria (Dorea, Shigella, Alistipes, Paraprevotella, Bacteroides, Sutterella, Turicibacter, Bifidobacterium, Clostridium, Allobaculum), significantly influencing arginine biosynthesis. Therefore, LP-CBT treatment regulated invertases and metabolites associated with the arginine pathway (carbamoyl phosphate, carboxymethyl proline, L-lysine, 10,11-epoxy-3-geranylgeranylindole, n-(6)-[(indol-3-yl)acetyl]-L-lysine, citrulline, N2-succinyl-L-ornithine, and (5-L-glutamyl)-L-glutamate). Furthermore, the inhibitory effect of LP-CBT on colorectal cancer was further confirmed using the MC38 subcutaneous tumor model. Collectively, these findings offer compelling evidence supporting the potential of LP-CBT as a viable preventive strategy against CRC.
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Colitis , Neoplasias Colorrectales , Microbioma Gastrointestinal , Lactobacillus plantarum , Animales , Ratones , Lactobacillus plantarum/metabolismo , Lisina/farmacología , Citocinas/metabolismo , Metaboloma , Neoplasias Colorrectales/metabolismo , Arginina/metabolismo , Sulfato de Dextran/farmacología , Modelos Animales de Enfermedad , Colitis/microbiología , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: Due to the global increase in aging populations and changes in modern lifestyles, the prevalence of neurodegenerative diseases, cerebrovascular disorders, neuropsychiatrcic conditions, and related ailments is rising, placing an increasing burden on the global public health system. MATERIALS AND METHODS: All studies on tetramethylpyrazine (TMP) and its derivatives were obtained from reputable sources such as PubMed, Elsevier, Library Genesis, and Google Scholar. Comprehensive data on TMP and its derivatives was meticulously compiled. RESULTS: This comprehensive analysis explains the neuroprotective effects demonstrated by TMP and its derivatives in diseases of the central nervous system. These compounds exert their influence on various targets and signaling pathways, playing crucial roles in the development of various central nervous system diseases. Their multifaceted mechanisms include inhibiting oxidative damage, inflammation, cell apoptosis, calcium overload, glutamate excitotoxicity, and acetylcholinesterase activity. CONCLUSION: This review provides a brief summary of the most recent advancements in research on TMP and its derivatives in the context of central nervous system diseases. It involves synthesizing analogs of TMP and evaluating their effectiveness in models of central nervous system diseases. The ultimate goal is to facilitate the practical application of TMP and its derivatives in the future treatment of central nervous system diseases.
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Enfermedades del Sistema Nervioso Central , Neuroprotección , Humanos , Acetilcolinesterasa , Enfermedades del Sistema Nervioso Central/tratamiento farmacológico , Pirazinas/farmacología , Pirazinas/uso terapéuticoAsunto(s)
Quemaduras , Exosomas , MicroARNs , Humanos , Quemaduras/terapia , Piel , Cicatrización de Heridas , FibroblastosRESUMEN
The Chinese herb Qianghuo is an antiphlogistic herb with many effects and complex components. In this study, the chemical composition of Qianghuo and its components in rat plasma after oral administration were investigated using ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). The extracts, blank plasma, and plasma containing the drug were analyzed by mass spectrometry, and data collected in both positive and negative ion modes were analyzed using Masslynx software, and the structures were confirmed by combining the compound fragment ions and mass spectrometry cleavage pathways. A total of 62 in vitro chemical components were identified, including 27 coumarins, 18 organic acids, 5 amino acids, 5 glycosides, 2 flavonoids, 4 nucleotides, and 1 ester, which were summarized from the obtained compounds in terms of their possible cleavage patterns. Among the identified 31 compounds in rat plasma, 21 were prototypes, mostly coumarins, organic acids, and flavonoids, and 10 were metabolites, which were mainly generated via hydroxylation and methylation pathways. Based on these, this study provides a theoretical foundation for quality control and basic research on Qianghuo medicinal substances.
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Medicamentos Herbarios Chinos , Espectrometría de Masas en Tándem , Ratas , Animales , Espectrometría de Masas en Tándem/métodos , Medicamentos Herbarios Chinos/química , Cromatografía Líquida de Alta Presión/métodos , Estructura Molecular , Flavonoides/análisis , Ácidos , Cumarinas/análisisRESUMEN
Atherosclerosis is the main underlying pathology of many cardiovascular diseases and is marked by plaque formation in the artery wall. It has posed a serious threat to the health of people all over the world. CD36 acts as a significant regulator of lipid homeostasis, which is closely associated with the onset and progression of atherosclerosis and may be a new therapeutic target. The abnormal overexpression of CD36 facilitates lipid accumulation, foam cell formation, inflammation, endothelial apoptosis, and thrombosis. Numerous natural products and lipid-lowering agents are found to target the suppression of CD36 or inhibit the upregulation of CD36 to prevent and treat atherosclerosis. Here, the structure, expression regulation and function of CD36 in atherosclerosis and its related pharmacological therapies are reviewed. This review highlights the importance of drugs targeting CD36 suppression in the treatment and prevention of atherosclerosis, in order to develop new therapeutic strategies and potential anti-atherosclerotic drugs both preclinically and clinically.
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Aterosclerosis , Humanos , Aterosclerosis/metabolismo , Células Espumosas/metabolismo , Regulación hacia Arriba , Inflamación/metabolismo , Lípidos , Lipoproteínas LDL/metabolismoRESUMEN
Introduction: Many challenges remain for long-term survival of renal allografts. Once-daily sirolimus (SRL) combined with low-dose extended-release tacrolimus (LER-TAC) may improve medication adherence and reduce the potential nephrotoxicity of calcineurin inhibitors (CNI) compared with standard immunosuppression regimens, thus potentially improving long-term graft survival. Methods: This retrospective, observational, single-center, propensity score matching (PSM) study compared conversion to SRL combined with low-dose ER-TAC and mycophenolic acid (MPA) combined with standard-dose TAC in kidney transplant recipients. After PSM, there were 56 patients in each group. Efficacy, safety, and medication adherence were evaluated over 12 months. Results: There was no significant difference between the two groups in terms of graft and recipient survival and incidence of biopsy-proven acute rejection (p = 1.000), and none of the recipients developed dnDSA after conversion. The mean eGFR improved in SRL + LER-TAC group after conversion compared to before conversion (51.12 ± 20.1 ml/min/1.73 m2 vs. 56.97 ± 19.23 ml/min/1.73 m2, p < 0.05). The medication adherence at 12 months after conversion was superior to before conversion (p = 0.002). Discussion: Our findings suggest that an immunosuppressive regimen of SRL combined with low-dose ER-TAC is no less effective and safe than standard immunosuppressive regimens for renal transplant recipients and may improve graft renal function and medication adherence.
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Chemotherapy is one of the main options in clinical tumor treatment. Although chemotherapy drugs have a good therapeutic effect, they can also cause a series of adverse reactions, such as neurotoxicity. Chemotherapy-induced neurotoxicity is a dose-limi-ting adverse reaction that significantly affects patients' long-term treatment and quality of life. This article reviewed literature from 2000 to the present on chemotherapy-induced neurotoxicity and found that oxaliplatin was the most frequently used chemotherapy drug. Based on the clinical characteristics of oxaliplatin-induced neurotoxicity, this article summarized the understanding of its pathogenesis from both traditional Chinese medicine(TCM) and western medicine perspectives, discussed the role and mechanism of TCM compounds and monomeric components, and explored the research direction of using cutting-edge biotechnology to reveal the mechanism of oxaliplatin-induced neurotoxicity from a temporal-spatial perspective of intercellular communication and the application prospects of an interdisciplinary model combining TCM pathogenesis, western medicine manifestations, and artificial intelligence in precise intervention decision-making for TCM, aiming to provide research ideas for the prevention and treatment of oxaliplatin-induced neurotoxicity and the development of new drugs.
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Antineoplásicos , Medicamentos Herbarios Chinos , Humanos , Medicina Tradicional China , Oxaliplatino/efectos adversos , Inteligencia Artificial , Calidad de Vida , Medicamentos Herbarios Chinos/uso terapéutico , Antineoplásicos/efectos adversos , CogniciónRESUMEN
Recent studies have suggested that ubiquitin-conjugating enzyme E2D1 (UBE2D1) is involved in tumor progression. In this study, we found that UBE2D1 expression was upregulated in breast cancer (BC) and was related to the prognosis of BC patients. Through in vitro and in vivo experiments, we demonstrated the aberrant expression of UBE2D1 promoted the proliferation and migration of BC cells, and the IGF2BP2-mediated N6-methyladenosine (m6A) modification increased the stability of UBE2D1 mRNA. Mechanistically, UBE2D1 expression regulated the activity of TGF-ß signaling through modulating the expression and the phosphorylation level of Smad2/3. Furthermore, UBE2D1 directly bound to Smad2/3 and affected the subsequent binding of Smad2 and Smad3, which is a necessary step for TGF-ß signaling activation. Thus, our study reveals a pro-oncogenic role of UBE2D1 in the progression of BC and may provide novel strategies for BC treatment.
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Failure to achieve target-specific delivery to ischemic brain sites has hampered the clinical efficacy of newly developed therapies for ischemic stroke. Emodin, an active ingredient isolated from traditional Chinese medicine, has been indicated to alleviate ischemic stroke; however, the underlying mechanism remains unclear. In this study, we aimed to achieve brain-targeted delivery of emodin to maximize its therapeutic efficacy and elucidate the mechanisms by which emodin alleviates ischemic stroke. A polyethylene glycol (PEG)/cyclic Arg-Gly-Asp (cRGD)-modified liposome was used to encapsulate emodin. TTC, HE, Nissl staining, and immunofluorescence staining were employed to evaluate the therapeutic efficacy of brain-targeting emodin in MCAO and OGD/R models. Inflammatory cytokine levels were determined using ELISA. Immunoprecipitation, immunoblotting, and RT-qPCR were utilized for clarifying the changes in key downstream signaling. Lentivirus-mediated gene restoration was employed to verify the core effector of emodin for relieving ischemic stroke. Encapsulating emodin in a PEG/cRGD-modified liposome enhanced its accumulation in the infarct region and substantially raised its therapeutic efficacy. Furthermore, we demonstrated that AQP4, the most abundant water transporter subunit expressed in astrocytes, plays a crucial role in mediating the mechanisms by which emodin inhibits astrocyte swelling, neuroinflammatory blood-brain barrier (BBB) breakdown in vivo and in vitro, and brain edema in general. Our study unveiled the critical target of emodin responsible for alleviating ischemic stroke and a localizable drug delivery vehicle in the therapeutic strategy for ischemic stroke and other brain injuries.
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INTRODUCTION: China's antidrug measures have been slowly shifting from police-intervention and punitive approaches to supportive services. However, the system is still highly stigmatizing. Helpline services emerged to engage drug users, families, and friends and provide needed support as they seek rehabilitation. This study aimed to explore service needs expressed during helpline calls, operators' use of techniques when responding to different needs, and operators' experiences working at and views toward the helpline. METHODS: We conducted a qualitative mixed-method study using two sources of data. One source was 47 call recordings collected at a drug helpline in China, and the other was five individual and two focus group interviews conducted with 18 helpline operators. Using a six-step thematic analysis method, we explored the patterns of needs expression and response, and the operators' experiences of interacting with callers. RESULTS: We found that typical callers were drug users and their relatives or friends. Interactions between the callers and operators involved the expression of and response to needs that emerged from involvement with drugs. Informational and emotional needs were the most common. Operators would respond to these needs with different counseling techniques, such as providing information, advising, normalizing, focusing, and instilling hope. The operators developed a system of practices, such as internal supervision, case summaries, and listening back, to enhance competence and ensure quality of services. The helpline work also prompted their critical reflections on the current antidrug system and gradually reshaped their views toward the population they serve. CONCLUSIONS: Antidrug workers who engaged in answering helpline calls employed varying techniques to facilitate callers' expressed needs. They helped by providing much-needed informational and emotional support for drug users, families, and friends. Helpline services opened a private channel for people involved in drug use to express their needs and seek formal help in China's still stigmatizing and punitive antidrug system. Experiences working with anonymous help-seekers outside the statutory rehabilitation system helped workers at the helpline to gain unique reflective insight into the antidrug system and drug users.
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Líneas Directas , Árboles , Humanos , Investigación Cualitativa , Consejo/métodos , Percepción AuditivaRESUMEN
Hypertrophic lysosomes are critical for tumor progression and drug resistance; however, effective and specific lysosome-targeting compounds for cancer therapy are lacking. Here we conducted a lysosomotropic pharmacophore-based in silico screen in a natural product library (2,212 compounds), and identified polyphyllin D (PD) as a novel lysosome-targeted compound. PD treatment was found to cause lysosomal damage, as evidenced by the blockade of autophagic flux, loss of lysophagy, and the release of lysosomal contents, thus exhibiting anticancer effects on hepatocellular carcinoma (HCC) cell both in vitro and in vivo. Closer mechanistic examination revealed that PD suppressed the activity of acid sphingomyelinase (SMPD1), a lysosomal phosphodieserase that catalyzes the hydrolysis of sphingomyelin to produce ceramide and phosphocholine, by directly occupying its surface groove, with Trp148 in SMPD1 acting as a major binding residue; this suppression of SMPD1 activity irreversibly triggers lysosomal injury and initiates lysosome-dependent cell death. Furthermore, PD-enhanced lysosomal membrane permeabilization to release sorafenib, augmenting the anticancer effect of sorafenib both in vivo and in vitro. Overall, our study suggests that PD can potentially be further developed as a novel autophagy inhibitor, and a combination of PD with classical chemotherapeutic anticancer drugs could represent a novel therapeutic strategy for HCC intervention.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Sorafenib/farmacología , Esfingomielina Fosfodiesterasa/farmacología , Neoplasias Hepáticas/metabolismo , Lisosomas/metabolismo , Autofagia , Resistencia a Medicamentos , PuncionesRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Sennoside A is a natural anthraquinone component mainly derived from rhubarb and has been routinely used as a clinical stimulant laxative. However, long-term application of sennoside A may lead to drug resistance and even adverse reactions, thus limiting its clinical use. Therefore, to reveal the time-dependent laxative effect and potential mechanism of sennoside A is of critical importance. AIM OF THE STUDY: This study was conducted to investigate the time-dependent laxative effect of sennoside A and unveil its underlying mechanism from the perspective of gut microbiota and aquaporins (AQPs). MATERIALS AND METHODS: Based on a mouse constipation model, 2.6 mg/kg sennoside A was administered orally for 1, 3, 7, 14 and 21 days, respectively. The laxative effect was assessed by the fecal index and fecal water content, the histopathology of the small intestine and colon was evaluated by hematoxylin-eosin staining. Gut microbiota changes was observed by 16S rDNA sequencing, and colonic AQPs expression was analyzed by quantitative real-time polymerase chain reaction and western blotting. Partial least-squares regression (PLSR) was used to screen out the effective indicators contributing to the laxative effect of sennoside A. The effective indicators were then fitted to time by a drug-time curve model to analyze the trend of efficacy of sennoside A, and the optimal time of administration was derived by comprehensive analysis with a three-dimensional (3D) time-effect image. RESULTS: Sennoside A had a significant laxative effect at 7 days of administration with no pathological changes in the small intestine or colon; however, at 14 or 21 days of administration, the laxative effect diminished and slight damage to the colon was observed. Sennoside A affects the structure and function of gut microbes. The alpha diversity showed that the abundance and diversity of gut microorganisms reached the highest value after 7 days of administration. Partial least squares discriminant analysis showed that the composition of the flora was close to normal when administered for less than 7 days, but was closest to the composition of constipation over 7 days. The expression of aquaporin 3 (AQP3) and aquaporin 7 (AQP7) decreased gradually after the administration of sennoside A, with the lowest expression at 7 days, and then increased gradually afterwards, while the expression of aquaporin 1 (AQP1) was the opposite. The PLSR results showed that AQP1, AQP3, Lactobacillus, Romboutsia, Akkermansia and UCG_005 contributed more to the laxative effect of the fecal index, and after fitting with the drug-time curve model, each index showed a trend of increasing and then decreasing. The comprehensive evaluation of the 3D time-effect image concluded that the laxative effect of sennoside A reached its best after 7 days of administration. CONCLUSION: Sennoside A should be used in regular dosages for less than one week, as it provides significant relief of constipation and exhibits no colonic damage within 7 days of administration. In addition, Sennoside A exerts its laxative effect by regulating gut microbiota of Lactobacillus Romboutsia, Akkermansia and UCG_005 and water channels of AQP1 and AQP3.
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Acuaporinas , Microbioma Gastrointestinal , Rheum , Ratones , Animales , Laxativos/farmacología , Laxativos/química , Senósidos/farmacología , Acuaporinas/genética , Acuaporinas/metabolismo , Estreñimiento/inducido químicamente , Estreñimiento/tratamiento farmacológico , Acuaporina 3/metabolismoRESUMEN
Objective: Programmed cell death 6 (PDCD6), a Ca 2+-binding protein, has been reported to be aberrantly expressed in all kinds of tumors. The aim of this study was to explore the role and mechanism of PDCD6 in hepatocellular carcinomas (HCCs). Methods: The expression levels of PDCD6 in liver cancer patients and HCC cell lines were analyzed using bioinformatics and Western blotting. Cell viability and metastasis were determined by methylthiazol tetrazolium (MTT) and transwell assays, respectively. And Western blotting was used to test related biomarkers and molecular pathway factors in HCC cell lines. LY294002, a PI3K inhibitor inhibiting AKT, was used to suppress the AKT/GSK3ß/ß-catenin pathway to help evaluate the role of this pathway in the HCC carcinogenesis associated with PDCD6. Results: The analysis of The Cancer Genome Atlas Database suggested that high PDCD6 expression levels were relevant to liver cancer progression. This was consistent with our finding of higher levels of PDCD6 expression in HCC cell lines than in normal hepatocyte cell lines. The results of MTT, transwell migration, and Western blotting assays revealed that overexpression of PDCD6 positively regulated HCC cell proliferation, migration, and invasion. Conversely, the upregulation of PDCD6 expression in the presence of an AKT inhibitor inhibited HCC cell proliferation, migration, and invasion. In addition, PDCD6 promoted HCC cell migration and invasion by epithelial-mesenchymal transition. The mechanistic investigation proved that PDCD6 acted as a tumor promoter in HCC through the AKT/GSK3ß/ß-catenin pathway, increasing the expression of transcription factors and cellular proliferation and metastasis. Conclusion: PDCD6 has a tumor stimulative role in HCC mediated by AKT/GSK3ß/ß-catenin signaling and might be a potential target for HCC progression.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Glucógeno Sintasa Quinasa 3 beta/genética , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Línea Celular , Proliferación Celular , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Proteínas de Unión al Calcio/genética , Proteínas de Unión al Calcio/metabolismo , Proteínas Reguladoras de la Apoptosis/genéticaRESUMEN
Objective: To study the effectiveness and feasibility of cryogenic disinfectants in different cold scenarios and analyze the key points of on-site cryogenic disinfection. Methods: Qingdao and Suifenhe were selected as application sites for the manual or mechanical spraying of cryogenic disinfectants. The same amount of disinfectant (3,000 mg/L) was applied on cold chain food packaging, cold chain containers, transport vehicles, alpine environments, and article surfaces. The killing log value of the cryogenic disinfectant against the indicator microorganisms ( Staphylococcus aureus and Escherichia coli) was used to evaluate the on-site disinfection effect. Results: When using 3,000 mg/L with an action time of 10 min on the ground in alpine regions, the surface of frozen items, cold-chain containers, and cold chain food packaging in supermarkets, all external surfaces were successfully disinfected, with a pass rate of 100%. The disinfection pass rates for cold chain food packaging and cold chain transport vehicles of centralized supervised warehouses and food processing enterprises were 12.5% (15/120), 81.67% (49/60), and 93.33% (14/15), respectively; yet, the surfaces were not fully sprayed. Conclusion: Cryogenic disinfectants are effective in disinfecting alpine environments and the outer packaging of frozen items. The application of cryogenic disinfectants should be regulated to ensure that they cover all surfaces of the disinfected object, thus ensuring effective cryogenic disinfection.
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Desinfectantes , Infecciones Estafilocócicas , Humanos , Desinfectantes/farmacología , Desinfección , Escherichia coli , Staphylococcus aureusRESUMEN
OBJECTIVES: Global epidemiological evidence indicates high rates of mental illness but low rates of diagnosis among older people. In China, service providers identify older adults with mental disorders in varied ways. Taking Shanghai as an example, this study revealed how the identification methods of geriatric mental health disorders in nonspecialized institutions diverge, providing a reference for the integration of services. METHODS: A purposive sampling method was adopted to conduct semi-structured interviews with 24 service providers from various nonspecialized geriatric mental health care institutions. Interview audio was recorded with consent and converted into verbatim transcripts. The interview data were analysed thematically. RESULTS: Although service providers from the health care system tended to apply a biomedical-oriented assessment, those from the social care system typically identified mental disorders among older people based on selective attention and interpersonal relationships. Although there are stark differences, the various identification mechanisms implicitly converge-the relationship with clients has become an important consideration. CONCLUSION: Geriatric mental health issues urgently require the integration of formal and informal care resources. Referring to the idea of task transfer, social identification mechanisms are expected to be a useful supplement to traditional biomedical-oriented identification.