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1.
J Ethnopharmacol ; 328: 118000, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38527574

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoer Niuhuang Qingxin Powder (XNQP) is a classic traditional Chinese medicine formula with significant clinical efficacy for treating febrile convulsions and influenza. AIM OF THE STUDY: This study aims to explore the potential mechanisms of XNQP in combating combating the influenza A virus, providing a theoretical basis for its clinical application. MATERIALS AND METHODS: The present investigation employed network pharmacology and bioinformatics analysis to determine the TLR4/MyD88/NF-κB signaling pathway as a viable target for XNQP intervention in IAV infection.Subsequently, a mouse model of influenza A virus infection was established, and different doses of XNQP were used for intervention. The protein expression levels of TLR4/MyD88/NF-κB were detected using HE staining, Elisa, immunohistochemistry, immunofluorescence, and western blot. RESULTS: The results showed that treatment with XNQP after IAV infection reduced the mortality and prolonged the survival time of infected mice. It reduced the release of TNF-α and IFN-γ in the serum and alleviated pathological damage in the lung tissue following infection. Additionally, the levels of TLR4, MyD88, NF-κB, and p-NF-κB P65 proteins were significantly reduced in lung tissue by XNQP. The inhibitory effect of XNQP on the expression of MyD88 and NF-κB was antagonized when TLR4 signaling was overexpressed. Consequently, the expression levels of MyD88, NF-κB, and p-NF-κB P65 were increased in lung tissue. Conversely, the expression levels of the proteins MyD88, NF-κB, and p-NF-κB P65 were downregulated when TLR4 signaling was inhibited. CONCLUSIONS: XNQP alleviated lung pathological changes, reduced serum levels of inflammatory factors, reduced mortality, and prolonged survival time in mice by inhibiting the overexpression of the TLR4/MyD88/NF-κB signaling pathway in lung tissues after IAV infection.


Asunto(s)
Medicamentos Herbarios Chinos , Virus de la Influenza A , Gripe Humana , Ratones , Animales , Humanos , FN-kappa B/metabolismo , Receptor Toll-Like 4/metabolismo , Factor 88 de Diferenciación Mieloide/metabolismo , Polvos , Transducción de Señal
2.
Phytother Res ; 38(5): 2462-2481, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38444049

RESUMEN

Alzheimer's disease (AD) is a neurodegenerative disorder where oxidative stress, induced by ferroptosis, has been linked to neuronal damage and cognitive deficits. The objective of this study is to investigate if the potential therapeutic agent, Curculigoside (CUR), could ameliorate AD by inhibiting ferroptosis. The potential therapeutic targets, such as GPX4 and SLC7A11, were identified using weighted gene co-expression network analysis (WGCNA). Concurrently, CUR was also screened against these potential targets using various analytical methods. For the in vivo studies, intragastric administration of CUR significantly ameliorated cognitive impairment in AD model mice induced by scopolamine and okadaic acid (OA). In vitro, CUR protected neuronal cells by altering the levels of ferroptosis-related specific markers in OA and scopolamine-induced neurotoxicity. The administration of CUR through intragastric route significantly reduced the levels of AD-promoting factors (such as Aß1-42, p-tau) and ferroptosis-promoting factors in the hippocampus and cortex of AD mice. Furthermore, CUR up-regulated the expression of GPX4 and decreased the expression of SLC7A11 in the ferroptosis signaling pathway, thereby increasing the ratio of glutathione (GSH)/oxidized glutathione (GSSG) in vivo and vitro. In conclusion, the cumulative results suggest that the natural compound CUR may serve as a promising therapeutic agent to ameliorate AD by inhibiting ferroptosis.


Asunto(s)
Enfermedad de Alzheimer , Benzoatos , Modelos Animales de Enfermedad , Ferroptosis , Glucósidos , Lignanos , Estrés Oxidativo , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Ferroptosis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratones , Glucósidos/farmacología , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Masculino , Lignanos/farmacología , Sistema de Transporte de Aminoácidos y+/metabolismo , Péptidos beta-Amiloides/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Medicina Tradicional China , Ratones Endogámicos C57BL , Medicamentos Herbarios Chinos/farmacología
4.
Environ Res ; 247: 118167, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38262514

RESUMEN

Sewage sludge incineration ash (SSIA) is rich in phosphorus (P), thus being considered as a reliable source of phosphorus recovery. Different P species behaved significant bioavailability. Based on this, a comprehensive investigation into the bioavailability transition path of P species during sewage sludge (SS) incineration was conducted. P predominantly existed in the form of inorganic phosphorus (IP) in SS with a higher concentration of non-apatite inorganic phosphorus (NAIP) and less concentration of apatite inorganic phosphorus (AP). During the SS incineration process, OP existed in the flocs and cell structures of SS underwent destruction, the released P then combined with metal elements such as Ca, Mg, Fe, and Al to form AP species (Ca/Mg-P) and NAIP species (Fe/Al/Mn-P), and the NAIP decomposition to release into gas phase. This was the initial step for enhancing the bioavailability of P species. As temperature increased and the incineration process progressed, the low-temperature-resistant NAIP dissociated, and the metal-binding sites of Al, Fe and Mn in NAIP species were gradually replaced by the Ca and Mg thus forming thermal stability AP species (Ca/Mg-P, such as CaHPO4, Ca2PO4Cl, and Mg3(PO4)2 et al.). This step was crucial for the bioavailability improvement of P species during the incineration process. Therefore, the IP proportions in TP were extremely high (>98%), and this value gradually increased as incineration temperature raised. The higher incineration temperature, the lower NAIP concentration and higher AP concentration. Besides, additives such as coal/rice husk/eggshell played a significant affect. Additives wither higher Ca content were inclined to react with P to form Ca/Mg-P (AP), while the presence of SO2 would react with Ca metals to form CaSO4 thus inhibiting the formation of AP species (such as CaHPO4 and CaPO4Cl). This results could provide theoretical support for the efficient and directional migration of P during sewage sludge incineration.


Asunto(s)
Fósforo , Aguas del Alcantarillado , Disponibilidad Biológica , Incineración , Calor
5.
Food Chem ; 438: 137400, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38039864

RESUMEN

The digestion behavior of lipids plays a crucial role in their nutritional bioaccessibility, which subsequently impacts human health. This study aims to investigate potential variations in lipid digestion profiles among individuals of different ages, considering the distinct physiological functions of the gastrointestinal tract in infants, aging populations, and healthy young adults. The digestion fates of high oleic peanut oil (HOPO), sunflower oil (SO), and linseed oil (LINO) were investigated using in vitro digestion models representing infants, adults, and elders. Comparatively, lipid digestion proved to be more comprehensive in adults, leading to free fatty acid (FFA) levels of 64.53%, 62.32%, and 57.90% for HOPO, SO, and LINO, respectively. Besides, infants demonstrated propensity to selectively release FFAs with shorter chain lengths and higher saturation levels during the digestion. In addition, in the gastric phase, particle sizes among the elderly were consistently larger than those observed in infants and adults, despite adults generating approximately 15% FFAs within the stomach. In summary, this study enhances our fundamental comprehension of how lipids with varying degrees of unsaturation undergo digestion in diverse age groups.


Asunto(s)
Ácidos Grasos no Esterificados , Aceite de Linaza , Humanos , Anciano , Aceite de Girasol , Tracto Gastrointestinal , Aceite de Cacahuete , Digestión/fisiología
6.
Int Urol Nephrol ; 56(1): 103-120, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37659995

RESUMEN

PURPOSE: To investigate the effectiveness and safety of device-assisted intravesical chemotherapy compared to Bacillus Calmette-Guerin (BCG) in the treatment of patients with intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC). METHODS: In February 2023, a systematic search was conducted on the PubMed, Cochrane, and Embase databases. Following the PRISMA guidelines, a systematic review and meta-analysis of the primary outcomes of interest were performed. The review was prospectively registered on PROSPERO under the registration number CRD42023398559. RESULTS: A total of 10 studies involving 1160 patients were included. The results of the meta-analysis showed that compared to BCG, device-assisted chemotherapy had a lower recurrence rate (OR: 0.63, 95% CI: 0.48-0.84, p = 0.001), longer recurrence-free survival (OR: 0.64, 95% CI: 0.47-0.88, p = 0.006), and lower incidence of fever (OR: 0.18, 95% CI: 0.08-0.44, p = 0.0002). However, no significant differences were observed between the two groups in terms of progression, overall survival, progression-free survival, disease-free survival, overall adverse events, serious adverse events, hematuria, allergy, and general discomfort. Subgroup analysis revealed that neither chemohyperthermia (CHT) nor electromotive drug administration (EMDA) showed statistically significant differences in oncological outcomes compared to BCG. Regarding adverse events, both CHT and EMDA groups showed lower rates of fever compared to the BCG group (OR: 0.26, 95% CI: 0.10-0.67, p = 0.005, and OR: 0.14, 95% CI: 0.05-0.37, p < 0.0001, respectively). No significant differences were observed in the remaining adverse events between either the CHT or EMDA group and the BCG group. CONCLUSION: Device-assisted intravesical chemotherapy appears to be a safe and viable alternative to BCG for patients with intermediate and high-risk NMIBC, showing comparable oncological outcomes and adverse events.


Asunto(s)
Vacuna BCG , Hipertermia Inducida , Neoplasias Vesicales sin Invasión Muscular , Humanos , Adyuvantes Inmunológicos , Administración Intravesical , Vacuna BCG/uso terapéutico , Invasividad Neoplásica , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Vesicales sin Invasión Muscular/tratamiento farmacológico
7.
Comput Biol Med ; 166: 107479, 2023 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-37783074

RESUMEN

OBJECTIVE: Chronic heart failure (CHF) is a complicated clinical syndrome with a high mortality rate. XiJiaQi (XJQ) is a traditional Chinese medicine used in the clinical treatment of CHF, but its bioactive components and their modes of action remain unknown. This study was designed to unravel the molecular mechanism of XJQ in the treatment of CHF using multiple computer-assisted and experimental methods. METHODS: Pharmacoinformatics-based methods were used to explore the active components and targets of XJQ in the treatment of CHF. ADMETlab was then utilized to evaluate the pharmacokinetic and toxicological properties of core components. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were to explore the underlying mechanism of XJQ treatment. Molecular docking, surface plasmon resonance (SPR), and molecular dynamics (MD) were employed to evaluate the binding of active components to putative targets. RESULTS: Astragaloside IV, formononetin, kirenol, darutoside, periplocin and periplocymarin were identified as core XJQ-related components, and IL6 and STAT3 were identified as core XJQ targets. ADME/T results indicated that periplocin and periplocymarin may have potential toxicity. GO and KEGG pathway analyses revealed that XJQ mainly intervenes in inflammation, apoptosis, diabetes, and atherosclerosis-related biological pathways. Molecular docking and SPR revealed that formononetin had a high affinity with IL6 and STAT3. Furthermore, MD simulation confirmed that formononetin could firmly bind to the site 2 region of IL6 and the DNA binding domain of STAT3. CONCLUSION: This study provides a mechanistic rationale for the clinical application of XJQ. Modulation of STAT3 and IL-6 by XJQ can impact CHF, further guiding research efforts into the molecular underpinnings of CHF.

8.
Exp Appl Acarol ; 91(3): 497-507, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37870735

RESUMEN

The repellent activity of Chinese cinnamon oil (Cinnamomum cassia) on nymphal ticks (Haemaphysalis longicornis Neumann, Rhipicephalus haemaphysaloides Supino, and Hyalomma asiaticum Schulze and Schlottke) was evaluated in a sample Y-tube bioassay. The results were based on the vertical migration of ticks during the host-seek phase and showed a dose-dependent repellent effect of Chinese cinnamon oil on the tested nymphs after 6 h. For H. longicornis, R. haemaphysaloides, and H. asiaticum at the concentrations (vol/vol) of 3, 3, and 1.5%, the repellent percentages over time were 68-97, 69-94, and 69-93%, respectively, which indicated strong repellent activities against ticks, similar to the positive control DEET (N,N-diethyl-3-methylbenzamide). Chinese cinnamon oil exerted the strongest effect on H. asiaticum nymphs. To our knowledge, this is the first study to investigate the repellent effects of Chinese cinnamon oil on ticks. Chinese cinnamon oil has considerable potential and should be developed as a practical tick repellent.


Asunto(s)
Cinnamomum aromaticum , Repelentes de Insectos , Ixodidae , Ninfa , Aceites Volátiles , Aceites de Plantas , Animales , Repelentes de Insectos/farmacología , Ixodidae/efectos de los fármacos , Ixodidae/crecimiento & desarrollo , Ninfa/efectos de los fármacos , Aceites Volátiles/farmacología , Rhipicephalus/efectos de los fármacos , Rhipicephalus/crecimiento & desarrollo , China , Aceites de Plantas/farmacología
9.
Zhongguo Zhong Yao Za Zhi ; 48(17): 4722-4730, 2023 Sep.
Artículo en Chino | MEDLINE | ID: mdl-37802811

RESUMEN

This study aims to investigate the regulatory effects of Astragalus polysaccharide(APS) and APS combined with 5-fluorouracil(5-FU) on indoleamine-2,3-dioxygenase(IDO1) in the colon tumor microenvironment. Sixty Balb/c mice were randomized into a blank group, a model group, an APS group, an APS + 5-FU group, an APS + low-dose 5-FU group, and a 5-FU group. A tumor model was established by subcutaneous transplantation with CT-26 mouse colon cancer cells in other groups except the blank group. After successful modeling, each group was treated with corresponding drugs for 7 days. The general condition, body weight, and tumor volume of the mice were observed and measured daily during the treatment period. The mice were sacrificed at the end of treatment, and the tumor suppression rate and spleen index of the mice were calculated. Western blot and fluorescence quantitative PCR were employed to determine the protein and mRNA levels, respectively, of IDO1 in the tumor tissue of mice. High performance liquid chromatography was employed to measure the levels of tryptophan(Trp) and kynurenine(Kyn) in the tumor tissue of mice. Hematoxylin-eosin(HE) staining was performed to observe the histological changes of the tumor tissue, and immunohistochemistry to detect the changes of CD4 and CD8 expression in the tumor tissue. Compared with that in the model group, the tumor volume of mice in each treatment group significantly reduced. The body weights of mice in APS + 5-FU group and 5-FU group significantly reduced from day 4 to day 7 of treatment. In addition, the APS + 5-FU group and 5-FU group showed significantly decreased spleen index. The protein and mRNA levels of IDO1 were significantly down-regulated in the APS, APS + 5-FU, and APS + low-dose 5-FU groups. The drug interventions significantly increased the Trp content and decreased the Kyn content. The APS + 5-FU group showed significantly reduced infiltration of CD4~+ T lymphocytes and increased infiltration of CD8~+ T lymphocytes. APS inhibited the expression of IDO1 in the colon tumor microenvironment to increase CD8~+ T lymphocyte infiltration, and the combination of APS with 5-FU demonstrated better effect.


Asunto(s)
Neoplasias del Colon , Microambiente Tumoral , Ratones , Animales , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genética , Fluorouracilo/farmacología , Polisacáridos/farmacología , Linfocitos T CD8-positivos/metabolismo , ARN Mensajero/metabolismo
10.
Front Oncol ; 13: 1190706, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37771438

RESUMEN

Objective: To profile the serum metabolites and metabolic pathways in colorectal cancer (CRC) patients associated with spleen-deficiency and qi-stagnation syndrome (SDQSS) or damp-heat syndrome (DHS). Methods: From May 2020 to January 2021, CRC patients diagnosed with traditional Chinese medicine (TCM) syndromes of SDQSS or DHS were enrolled. The clinicopathological data of the SDQSS and DHS groups were compared. The serum samples were analyzed by liquid chromatography-mass spectrometry (LC-MS). The variable importance in the projection >1, fold change ≥3 or ≤0.333, and P value ≤0.05 were used to identify differential metabolites between the two groups. Furthermore, areas under the receiver operating characteristic (ROC) curve > 0.9 were applied to select biomarkers with good predictive performance. The enrichment metabolic pathways were searched through the database of Kyoto Encyclopedia of Genes and Genomes. Results: 60 CRC patients were included (30 SDQSS and 30 DHS). The level of alanine aminotransferase was marginally significantly higher in the DHS group than the SDQSS group (P = 0.051). The other baseline clinicopathological characteristics were all comparable between the two groups. 23 differential serum metabolites were identified, among which 16 were significantly up-regulated and 7 were significantly down-regulated in the SDQSS group compared with the DHS group. ROC curve analysis showed that (S)-3-methyl-2-oxopentanoic acid, neocembrene, 1-aminocyclopropanecarboxylic acid, 3-methyl-3-hydroxypentanedioate, and nicotine were symbolic differential metabolites with higher predictive power. The top five enrichment signalling pathways were valine, leucine and isoleucine biosynthesis; lysosome; nicotine addiction; fructose and mannose metabolism; and pertussis. Conclusion: Our study identifies the differential metabolites and characteristic metabolic pathways among CRC patients with SDQSS or DHS, offering the possibility of accurate and objective syndrome differentiation and TCM treatment for CRC patients.

11.
Toxins (Basel) ; 15(8)2023 07 26.
Artículo en Inglés | MEDLINE | ID: mdl-37624235

RESUMEN

Deoxynivalenol (DON, Vomitoxin) is a threatening mycotoxin that mainly produces oxidative stress and leads to hepatotoxicity in poultry. Antioxidant dietary supplements dramatically boost immunity, safeguarding animals from DON poisoning. Luteolin (LUT) is an active plant-derived compound that poses influential antioxidants. This study explored the effectiveness of LUT in combination with activated charcoal (AC) in detoxifying DON in broilers. The 180 one-day broiler chickens were allocated into five different groups having six replicates in each group, provided with ad libitum feed during the trial period (28 days) as follows: in the control group, basal diet (feed with no supplementation of LUT, AC or DON); in group 2, a basal diet added with 10 mg/kg DON from contaminated culture (DON); in group 3, a basal diet augmented by 350 mg/kg LUT and DON 10 mg/kg (DON + LUT); in group 4, a basal diet supplemented by DON 10 mg/kg + AC 200 mg/kg (DON + AC); and in group 5, a basal diet supplemented by 10 mg/kg DON + 350 mg/kg LUT + 200 mg/kg AC (DON + LUT + AC). Concerning the control group, the DON-treated broilers demonstrated a significant decrease in growth performance (p < 0.05) and serum immunoglobulin (p < 0.05) contents, negatively changing the serum biochemical contents and enzymatic activities and an increase in histopathological liver lesions. Furthermore, DON substantially increased (p < 0.05) malondialdehyde (MDA) concentration and decreased total superoxide dismutase (T-SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) levels in the serum and liver. The intake of AC and LUT to the DON-contaminated diet decreased DON residue in the liver and potentially reduced the adverse effects of DON. Considering the results, supplementation of LUT with mycotoxin adsorbent has protective effects against mycotoxicosis caused by DON. It could be helpful for the development of novel treatments to combat liver diseases in poultry birds. Our findings may provide important information for applying LUT and AC in poultry production.


Asunto(s)
Antioxidantes , Pollos , Animales , Antioxidantes/farmacología , Carbón Orgánico/farmacología , Luteolina
12.
Nutrients ; 15(16)2023 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-37630835

RESUMEN

The impact of a Mediterranean diet on the intestinal microbiome has been linked to its health benefits. We aim to evaluate the effects of a Mediterranean diet supplemented with dairy foods on the gut microbiome in Australians at risk of cardiovascular disease. In a randomised controlled cross-over study, 34 adults with a systolic blood pressure ≥120 mmHg and with risk factors for cardiovascular disease were randomly allocated to a Mediterranean diet with 3-4 daily serves of dairy foods (Australian recommended daily intake (RDI) of 1000-1300 mg per day (MedDairy)) or a low-fat (LFD) control diet. Between each 8-week diet, participants underwent an 8-week washout period. Microbiota characteristics of stool samples collected at the start and end of each diet period were determined by 16S rRNA amplicon sequencing. MedDairy-associated effects on bacterial relative abundance were correlated with clinical, anthropometric, and cognitive outcomes. No change in the overall faecal microbial structure or composition was observed with either diet (p > 0.05). The MedDairy diet was associated with changes in the relative abundance of several bacterial taxa, including an increase in Butyricicoccus and a decrease in Colinsella and Veillonella (p < 0.05). Increases in Butyricicoccus relative abundance over 8 weeks were inversely correlated with lower systolic blood pressure (r = -0.38, p = 0.026) and positively correlated with changes in fasting glucose levels (r = 0.39, p = 0.019), specifically for the MedDairy group. No significant associations were observed between the altered taxa and anthropometric or cognitive measures (p > 0.05). Compared to a low-fat control diet, the MedDairy diet resulted in changes in the abundance of specific gut bacteria, which were associated with clinical outcomes in adults at risk of CVD.


Asunto(s)
Enfermedades Cardiovasculares , Dieta Mediterránea , Microbioma Gastrointestinal , Hipotensión , Adulto , Humanos , Estudios Cruzados , ARN Ribosómico 16S , Australia , Suplementos Dietéticos , Enfermedades Cardiovasculares/prevención & control , Clostridiaceae
13.
Adv Sci (Weinh) ; 10(27): e2301975, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37526345

RESUMEN

The Warburg effect-related metabolic dysfunction of the tricarboxylic acid (TCA) cycle has emerged as a hallmark of various solid tumors, particularly renal cell carcinoma (RCC). RCC is characterized by high immune infiltration and thus recommended for immunotherapeutic interventions at an advanced stage in clinical guidelines. Nevertheless, limited benefits of immunotherapy have prompted investigations into underlying mechanisms, leading to the proposal of metabolic dysregulation-induced immunoevasion as a crucial contributor. In this study, a significant decrease is found in the abundance of alpha-ketoglutarate (αKG), a crucial intermediate metabolite in the TCA cycle, which is correlated with higher grades and a worse prognosis in clinical RCC samples. Elevated levels of αKG promote major histocompatibility complex-I (MHC-I) antigen processing and presentation, as well as the expression of ß2-microglobulin (B2M). While αKG modulates broad-spectrum demethylation activities of histone, the transcriptional upregulation of B2M is dependent on the demethylation of H3K4me1 in its promoter region. Furthermore, the combination of αKG supplementation and PD-1 blockade leads to improved therapeutic efficacy and prolongs survival in murine models when compared to monotherapy. Overall, the findings elucidate the mechanisms of immune evasion in anti-tumor immunotherapies and suggest a potential combinatorial treatment strategy in RCC.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Animales , Ratones , Carcinoma de Células Renales/terapia , Carcinoma de Células Renales/patología , Receptor de Muerte Celular Programada 1 , Ácidos Cetoglutáricos , Neoplasias Renales/terapia , Inmunoterapia
14.
Chembiochem ; 24(20): e202300395, 2023 10 17.
Artículo en Inglés | MEDLINE | ID: mdl-37485551

RESUMEN

ß-Carboline alkaloids have a variety of pharmacological activities, such as antitumor, antibiosis and antidiabetes. Harmine and harmol are two structurally similar ß-carbolines that occur in many medicinal plants. In this work, we chose harmine and harmol to impede the amyloid fibril formation of human islet amyloid polypeptide (hIAPP) associated with type 2 diabetes mellitus (T2DM), by a series of physicochemical and biochemical methods. The results indicate that harmine and harmol effectively prevent peptide fibril formation and alleviate toxic oligomer species. In addition, both small molecules exhibit strong binding affinities with hIAPP mainly through hydrophobic and hydrogen bonding interactions, thus reducing the cytotoxicity induced by hIAPP. Their distinct binding pattern with hIAPP is closely linked to the molecular configuration of the two small molecules, affecting their ability to impede peptide aggregation. The study is of great significance for the application and development of ß-carboline alkaloids against T2DM.


Asunto(s)
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Polipéptido Amiloide de los Islotes Pancreáticos/química , Harmina , Amiloide/química
15.
Artículo en Inglés | MEDLINE | ID: mdl-37433697

RESUMEN

INTRODUCTION: We investigated the impact of the COVID-19 pandemic on annual adherence to seven diabetes care guidelines and risk factor management among people with diabetes. RESEARCH DESIGN AND METHODS: We included all adults (aged ≥18 years) with prevalent diabetes as of 1 January 2018, who were continuously enrolled at Kaiser Permanente Georgia (KPGA) through 31 December 2021 (n=22 854). Prevalent diabetes was defined as a history of at least one of a diagnosis code for diabetes, use of antihyperglycemic medication, or at least one laboratory value of HbA1c, fasting plasma glucose or random glucose in the diabetic range. We defined pre-COVID (2018-2019) and during COVID (2020-2021) cohorts. Cohort-specific laboratory measurements (ie, blood pressure (BP), HbA1c, cholesterol, creatinine, urine-albumin-creatinine ratio (UACR)) and procedures (ie, eye and foot examinations) were determined from KPGA's electronic medical record data. We used logistic generalized estimating equations (GEE), adjusted for baseline age, to assess the within-subject change in guideline adherence (ie, at least one measurement per year per period) from pre-COVID to during COVID era overall, and by age, sex, and race. Linear GEE compared mean laboratory measurements pre and during COVID. RESULTS: The proportion of adults meeting each of the seven diabetes care guidelines decreased significantly during (vs pre) COVID (range in absolute reductions: -0.8% to -11.2%) with greatest reductions seen for BP (-11.2%) and cholesterol (-8.8%). Declines were similar across age, sex, and race subgroups. Average HbA1c and systolic BP increased 0.11% and 1.6 mmHg, respectively, while low-density lipoprotein cholesterol declined 8.9 mg/dL. The proportion of adults at high risk of kidney disease (ie, UACR ≥300 mg/g) increased from 6.5% to 9.4%. CONCLUSIONS: In an integrated healthcare system, the proportion of people with diabetes meeting guideline-recommended screenings decreased during the pandemic, coinciding with worsening glucose, kidney, and (some) cardiovascular risk profiles. Follow-up is needed to assess the long-term implications of these care gaps.


Asunto(s)
COVID-19 , Diabetes Mellitus , Adulto , Humanos , Estados Unidos , Adolescente , Pandemias , Creatinina , Hemoglobina Glucada , COVID-19/epidemiología , Diabetes Mellitus/epidemiología
16.
Altern Ther Health Med ; 29(6): 50-55, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37442183

RESUMEN

Objective: To investigate the factors influencing lesion recurrence during the follow-up after cervical conization and evaluate the clinical value of human papillomavirus (HPV) testing and thinprep cytology test (TCT) in postoperative follow-up patients undergoing cervical conization. Methods: A total of 289 patients with cervical lesions who underwent primary cervical conization at our hospital between January 1, 2018, and December 31, 2019, were included in this study. TCT, HPV testing, and colposcopy were performed every 6 months for a follow-up period of 3 years. Based on the follow-up results, the patients were divided into recurrence and non-recurrence groups. The basic and colposcopic data of the two groups were analyzed to identify factors influencing lesion recurrence. Additionally, the clinical value of HPV testing and TCT in postoperative follow-up and recurrence diagnosis of patients undergoing cervical conization was assessed. Results: The recurrence group showed significantly higher age of onset, concurrent rate of other chronic diseases, and parity, as well as a markedly lower barrier contraceptive rate compared to the non-recurrence group, with statistically significant differences (P < .05). In the recurrence group, the type III transformation zone (TZ) predominated (59.26%), which significantly differed from the non-recurrence group (P < .05). The detection rates of abnormal TCT findings and HPV infections in postoperative reexaminations were significantly higher in the recurrence group compared to the non-recurrence group (P < .05), whereas no significant differences were observed between the two groups before cervical conization (P > .05). Among the recurrence group (n = 54), 52 cases (96.3%) had HPV infections, and 29 cases (53.7%) had abnormal TCT findings, with a significantly higher detection rate for HPV infections (P < .05). The area under the receiver operating characteristic (ROC) curve (AUC) for HPV testing, TCT, and combined HPV testing with TCT after cervical conization were 0.861, 0.712, and 0.882, respectively. These results indicate that HPV testing alone performs similarly to combined HPV testing with TCT and significantly outperforms TCT alone in predicting lesion recurrence after cervical conization. Conclusions: Factors influencing lesion recurrence after cervical conization include patient age, barrier contraceptive rate, concurrent rate of other chronic diseases, parity, and type of transformation zone. HPV testing alone is more sensitive and accurate than TCT in predicting lesion recurrence during postoperative follow-up of patients undergoing cervical conization. This finding can reduce missed diagnoses and provide a significant theoretical basis for postoperative follow-up of patients undergoing cervical conization.

17.
Fertil Steril ; 120(4): 922-924, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37499779

RESUMEN

OBJECTIVE: To report a patient with prolonged intermenstrual bleeding and a cystic mass at a cesarean scar treated with laparoscopic folding sutures and hysteroscopic canalization. DESIGN: A 4.0 cm-cystic mass formed at the uterine scar caused continuous menstrual blood outflow in the diverticulum and was treated with hysteroscopy combined with laparoscopy. SETTING: University hospital. PATIENTS: A 38-year-old woman of childbearing age who had undergone two cesarean sections and two abortions reported vaginal bleeding for 10 years, which began shortly after the second cesarean section. Curettage was performed, but no abnormality was found. The patient unsuccessfully tried to manage her symptoms with traditional Chinese medicine and hormone drugs. The muscular layer of the lower end of the anterior wall of the uterus was weak, and there were cystic masses on the right side. INTERVENTION: The bladder was stripped from the lower uterine segment under laparoscopy, and the surrounding tissue of the mass at the uterine scar was separated. The position of the cesarean scar defect was identified by hysteroscopy combined with laparoscopy, and the relationship between the uterine mass and surrounding tissues was analyzed. An electric cutting ring resection on both sides of the obstruction was performed to eliminate the valve effect. The active intima of the scar diverticulum was destroyed by electrocoagulation, followed by laparoscopic treatment of the uterine scar diverticulum mass. An intraoperative tumor incision revealed visible bloody fluid mixed with intimal material. The uterine scar diverticulum defect was repaired using 1-0 absorbable barbed continuous full-thickness mattress fold sutures. Finally, the bilateral round ligament length was adjusted so that the uterus tilted forward. MAIN OUTCOME MEASURES: Recovery of menstruation and anatomy of the uterine isthmus. RESULTS: The operation was successful, and the postoperative recovery was fast. There was no interphase bleeding at the 1-month follow-up, and the uterine scar diverticulum was repaired, with the thickness of the uterine scar muscle layer increasing to 0.91 cm. CONCLUSION: The simple, straightforward procedure to resolve the abnormal cystic, solid mass formed because of the continuous deposition of blood in the uterine scar diverticulum involved laparoscopic folding and docking sutures combined with hysteroscopic canal opening.


Asunto(s)
Divertículo , Laparoscopía , Humanos , Embarazo , Femenino , Niño , Adulto , Histeroscopía/métodos , Cicatriz/complicaciones , Cicatriz/diagnóstico , Cesárea/efectos adversos , Resultado del Tratamiento , Laparoscopía/métodos , Útero/patología , Divertículo/diagnóstico , Divertículo/cirugía , Divertículo/complicaciones
18.
Neurology ; 101(7): e699-e709, 2023 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-37349112

RESUMEN

BACKGROUND AND OBJECTIVES: The objective of this study was to propose a clustering approach to identify migraine subgroups and test the clinical usefulness of the approach by providing prognostic information for electroacupuncture treatment selection. METHODS: Participants with migraine without aura (MWoA) were asked to complete a daily headache diary, self-rating depression and anxiety, and quality-of-life questionnaires. Whole-brain functional connectivities (FCs) were assessed on resting-state functional MRI (fMRI). By integrating clinical measurements and fMRI data, partial least squares correlation and hierarchical clustering analysis were used to cluster participants with MWoA. Multivariate pattern analysis was applied to validate the proposed subgrouping strategy. Some participants had an 8-week electroacupuncture treatment, and the response rate was compared between different MWoA subgroups. RESULTS: In study 1, a total of 97 participants (age of 28.2 ± 1.0 years, 70 female participants) with MWoA and 77 healthy controls (HCs) (age of 26.8 ± 0.1 years, 61 female participants) were enrolled (dataset 1), and 2 MWoA subgroups were defined. The participants in subgroup 1 had a significantly lower headache frequency (times/month of 4.4 ± 1.1) and significantly higher self-ratings of depression (depression score of 49.5 ± 2.3) when compared with participants in subgroup 2 (times/month of 7.0 ± 0.6 and depression score of 43.4 ± 1.2). The between-group differences of FCs were predominantly related to the amygdala, thalamus, hippocampus, and parahippocampal area. In study 2, 33 participants with MWoA (age of 30.9 ± 2.0 years, 28 female participants) and 23 HCs (age of 29.8 ± 1.1 years, 13 female participants) were enrolled as an independent dataset (dataset 2). The classification analysis validated the effectiveness of the 2-cluster solution of participants with MWoA in datasets 1 and 2. In study 3, 58 participants with MWoA were willing to receive electroacupuncture treatment and were assigned to different subgroups. Participants in different subgroups exhibited different response rates (p = 0.03, OR CI 0.086-0.93) to electroacupuncture treatment (18% and 44% for subgroups 1 and 2, respectively). DISCUSSION: Our study proposed a novel clustering approach to define distinct MWoA subgroups, which could be useful for refining the diagnosis of participants with MWoA and guiding individualized strategies for pain prophylaxis and analgesia.


Asunto(s)
Electroacupuntura , Migraña sin Aura , Humanos , Femenino , Adulto , Encéfalo , Dolor , Cefalea , Imagen por Resonancia Magnética , Análisis por Conglomerados
20.
J Ethnopharmacol ; 315: 116642, 2023 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-37236381

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Arctium lappa L. is a common specie of Asteraceae. Its main active ingredient, Arctigenin (AG), in mature seeds exerts pharmacological effects on the Central Nervous System (CNS). AIM OF THE STUDY: To review studies on the specific effects of the AG mechanism on various CNS diseases and elucidate signal transduction mechanisms and their pharmacological actions. MATERIALS AND METHODS: This investigation reviewed the essential role of AG in treating neurological disorders. Basic information on Arctium lappa L. was retrieved from the Pharmacopoeia of the People's Republic of China. The related articles from 1981 to 2022 on the network database (including CNKI, PubMed, and Wan Fang and so on) were reviewed using AG and CNS diseases-related terms such as Arctigenin and Epilepsy. RESULTS: It was confirmed that AG has a therapeutic effect on Alzheimer's disease, Glioma, infectious CNS diseases (such as Toxoplasma and Japanese Encephalitis Virus), Parkinson's disease, Epilepsy, etc. In these diseases, related experiments such as a Western blot analysis revealed that AG could alter the content of some key factors (such as the reduction of Aß in Alzheimer's disease). However, in-vivo AG's metabolic process and possible metabolites are still undetermined. CONCLUSION: Based on this review, the existing pharmacological research has indeed made objective progress to elucidate how AG prevents and treats CNS diseases, especially senile degenerative disease such as Alzheimer's diseases. It was revealed that AG could be used as a potential nervous system drug as it has a wide range of effects in theory with markedly high application value, especially in the elder group. However, the existing studies are limited to in-vitro experiments; therefore, little is known about how AG metabolizes and functions in-vivo, limiting its clinical application and requiring further research.


Asunto(s)
Enfermedad de Alzheimer , Arctium , Lignanos , Humanos , Enfermedad de Alzheimer/tratamiento farmacológico , Lignanos/farmacología , Lignanos/uso terapéutico , Furanos/farmacología , Furanos/uso terapéutico , Transducción de Señal
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