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BACKGROUND: Moderate to severe breast pain has major effects on the quality of life for patients. Patent Chinese medicines are widely used in the treatment of breast pain due to their stable dosage form and good efficacy. OBJECTIVE: To evaluate the beneficial effects and safety of Hongjin Xiaojie Capsule (HJXJC), a Chinese patent medicine, for the treatment of cyclical breast pain. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This is a multicenter, single-blind randomized controlled trial conducted in 3 medical centers in China from 2019 to 2021. Patients with moderate to severe cyclic breast pain were randomly divided into the intervention group (who took HJXJC, four capsules per dose, three times a day for 12 weeks) and the control group (waiting for the treatment) in a 1:1 ratio. MAIN OUTCOME MEASURES: The primary outcome was pain duration, and the patients recorded measurements at baseline and at the end of weeks 4, 8, 12 and 16 on a patient log card. RESULTS: The full analysis set (FAS) population included 298 participants (intervention group, n = 150; control group, n = 148), while the per-protocol analysis set (PPS) included 274 participants. After 12 weeks, the duration of breast pain was significantly shorter in the intervention group (FAS: mean difference, -6.69; 95% CI, -7.58 to -5.80; P < 0.01, vs control. PPS: mean difference, -7.09; 95% CI, -8.01 to -6.16; P < 0.01, vs control). The Short-form McGill Pain Questionnaire (SF-MPQ) scores were significantly lower in the intervention group (FAS: mean difference, -12.55; 95% CI, -13.90 to -11.21; P < 0.01, vs control. PPS: mean difference, -13.07; 95% CI, -14.48 to -11.66; P < 0.01, vs control). The above indicators continued to be significantly different through week 16. Moreover, in the intervention group, breast lumps shrank after 12 weeks and the size of breast lumps was statistically smaller than that in the control group (P < 0.05), whereas the sizes of breast nodules and uterine fibroid showed no statistically significant difference compared with the control group (P > 0.05). At weeks 8 and 12, the dysmenorrhea scores in the intervention group were lower than those in the control group (P < 0.05). No obvious adverse reactions were observed in any group. CONCLUSION: HJXJC can significantly shorten the duration of breast pain, reduce breast pain, reduce the size of breast lumps, and relieve dysmenorrhea. However, it has no significant effect on the size of breast nodules or uterine fibroid. TRIAL REGISTRATION: This trial has been registered at the ISRCTN Registry. Number: ISRCTN44184398. PLEASE CITE THIS ARTICLE AS: Zhang Q, Fan YY, Wu XQ, Huo YD, Wang CH, Liang SB, Wang T, Zhong R, Wang X, Lai BY, Pei XH, Liu JP. Hongjin Xiaojie Capsule, a Chinese patent medicine, for treating moderate to severe cyclical breast pain: A single-blind randomized controlled trial. J Integr Med. 2024; Epub ahead of print.
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Background: Breast cancer lung metastasis occurs at a high rate and at an early stage, and is the leading cause of death in breast cancer patients. The aim of this study was to investigate the effect of Ru'ai Shuhou Recipe (RSR) intervention on the occurrence of recurrent metastases, especially lung metastases, in postoperative patients with breast cancer. Materials and Methods: A retrospective cohort study was implemented at Shuguang Hospital of Shanghai University of Traditional Chinese Medicine in China between January 2014 to January 2019. Female patients were included according to the propensity score matching (PSM) method and balanced on the basis of general and clinical information such as age, body mass index, neo-adjuvant therapy, and surgical approach. Patients with pathological diagnosis of breast cancer were included in this study. Breast cancer patients were divided into exposed and non-exposed groups according to whether they took RSR-based botanical drugs after surgery. Kaplan-Meier survival analysis and Cox survival analysis to explore the relationship between RSR and 5-year disease-free survival and incidence of lung metastases in breast cancer patients after surgery. Results: 360 female patients were assessed and 190 patients were included in the study after PSM (95 in each of the exposed and non-exposed groups). Of the 190 patients after PSM, 55.79% were over 50 years of age. The mean follow-up time was 60.55 ± 14.82 months in the exposed group and 57.12 ± 16.37 months in the non-exposed group. There was no significant baseline characteristics difference between two groups. Kaplan-Meier analysis showed that the 5-year incidence of lung metastases was significantly lower in the exposed group, and the disease-free survival of patients was significantly longer. Cox univariate and multivariate analysis showed that neoadjuvant chemotherapy and lymph node metastasis were independent risk factors for the development of breast cancer lung metastasis, with risk ratios of 17.188 and 5.812, while RSR treatment was an independent protective factor against the development of breast cancer lung metastasis, with a risk ratio of 0.290. Conclusion: Standard biomedical treatment combined with RSR intervention can better prevent breast cancer recurrence and metastasis, reduce the incidence of lung metastasis in patients, and improve long-term prognosis.
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BACKGROUND: Widespread neuropathic pain usually affects a wide range of body areas and inflicts huge suffering on patients. However, little is known about how it happens and effective therapeutic interventions are lacking. METHODS: Widespread neuropathic pain was induced by partial infraorbital nerve transection (p-IONX) and evaluated by measuring nociceptive thresholds. In vivo/vitro electrophysiology were used to evaluate neuronal activity. Virus tracing strategies, combined with optogenetics and chemogenetics, were used to clarify the role of remodeling circuit in widespread neuropathic pain. RESULTS: We found that in mice receiving p-IONX, along with pain sensitization spreading from the orofacial area to distal body parts, glutamatergic neurons in the ventral posteromedial nucleus of the thalamus (VPMGlu) were hyperactive and more responsive to stimulations applied to the hind paw or tail. Tracing experiments revealed that a remodeling was induced by p-IONX in the afferent circuitry of VPMGlu, notably evidenced by more projections from glutamatergic neurons in the dorsal column nuclei (DCNGlu). Moreover, VPMGlu receiving afferents from the DCN extended projections further to glutamatergic neurons in the posterior insular cortex (pIC). Selective inhibition of the terminals of DCNGlu in the VPM, the soma of VPMGlu or the terminals of VPMGlu in the pIC all alleviated trigeminal and widespread neuropathic pain. CONCLUSION: These results demonstrate that hyperactive VPMGlu recruit new afferents from the DCN and relay the extra-cephalic input to the pIC after p-IONX, thus hold a key position in trigeminal neuropathic pain and its spreading. This study provides novel insights into the circuit mechanism and preclinical evidence for potential therapeutic targets of widespread neuropathic pain.
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Núcleos Talámicos Ventrales , Animales , Ratones , Masculino , Neuralgia del Trigémino/fisiopatología , Neuralgia/fisiopatología , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Optogenética , Umbral del Dolor/fisiologíaRESUMEN
Objective: This study aimed to evaluate the therapeutic efficacy and safety of Dan'e Fukang soft extracts in moderate ovarian hyperstimulation syndrome (OHSS) for the simultaneous treatment of blood and fluid, guided by the traditional Chinese medicine principle of "triple prevention". Methods: This study conducted a retrospective analysis of clinical data from outpatients who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection embryo transfer (ICSI-ET). A total of 2245 cases were included and divided into a treatment group (1002 cases) and a control group (1243 cases). Patients in the treatment group were administered Dan'e Fukang soft extracts orally in addition to conventional Western medicine. Comparative assessments were made between the two groups on pelvic ascites volume, maximum ovary diameter, dysmenorrhea incidence post-oocyte retrieval, and safety indicators. Results: There were no statistically significant differences between the treatment group and the control group in terms of general characteristics or the levels of follicle-stimulating hormone (FSH), luteotropic hormone (LH), estradiol (E2), or progesterone (P) at the time of gonadotropin (Gn) initiation. The groups did not differ significantly when we compared the levels of LH, E2, or P on the day of human chorionic gonadotropin (hCG) injection and during ovarian hyperstimulation protocols (P > 0.05 for all indicators). The differences in the volume of pelvic ascites, the maximum ovarian diameter, and the incidence of dysmenorrhea after oocyte retrieval were statistically significant between the treatment group and the control group (P < 0.05 in both). There were no instances of adverse reactions in either group. Conclusion: Based on the traditional Chinese medicine principle of "triple prevention", the use of Dan'e Fukang soft extracts for the simultaneous treatment of blood and fluid in moderate OHSS significantly improved the absorption of pelvic ascites, promoted ovarian recovery, and reduced the incidence of dysmenorrhea after oocyte retrieval.
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Background: Granulomatous lobular mastitis (GLM) is a chronic inflammatory breast disease, and abscess formation is a common complication of GLM. The process of abscess formation is accompanied by changes in multiple inflammatory markers. The present study aimed to construct a diagnosis model for the early of GLM abscess formation based on multiple inflammatory parameters. Methods: Based on the presence or absence of abscess formation on breast magnetic resonance imaging (MRI), 126 patients with GLM were categorised into an abscess group (85 patients) and a non-abscess group (41 patients). Demographic characteristics and the related laboratory results for the 9 inflammatory markers were collected. Logistics univariate analysis and collinearity test were used for selecting independent variables. A regression model to predict abscess formation was constructed using Logistics multivariate analysis. Results: The univariate and multivariate analysis showed that the N, ESR, IL-4, IL-10 and INF-α were independent diagnostic factors of abscess formation in GLM (P<0. 05). The nomogram was drawn on the basis of the logistics regression model. The area under the curve (AUC) of the model was 0.890, which was significantly better than that of a single indicator and the sensitivity and specificity of the model were high (81.2% and 85.40%, respectively). These results predicted by the model were highly consistent with the actual diagnostic results. The results of this calibration curve indicated that the model had a good value and stability in predicting abscess formation in GLM. The decision curve analysis (DCA) demonstrated a satisfactory positive net benefit of the model. Conclusion: A predictive model for abscess formation in GLM based on inflammatory markers was constructed in our study, which may provide a new strategy for early diagnosis and treatment of the abscess stage of GLM.
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Background: Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a life-threatening infectious disease that has become a global pandemic. Objective: This study aimed to explore the effects of SARS-CoV-2 inactivated vaccine on the outcome of frozen embryo transfer (FET). Methods: We grouped patients who underwent FET between August 2021 and March 2022 based on their vaccination status, number of doses, and the interval between the last dose and the FET, and then compared the differences in pregnancy outcomes among the groups. Results: There were 1084 vaccinated patients and 1228 non-vaccinated ones. There were significant differences in the live birth rate between the vaccination and non-vaccination groups (16.61% vs 28.26%), among the one-dose, two-dose, and three-dose groups (22.28% vs 19.51% vs 7.27%), and among the groups with interval ≤ 1 month, 1-2 months, and ≥ 2 months (38.38% vs 27.27% vs 12.03%). There were significant differences in the persistent pregnancy rate between the vaccination and non-vaccination groups (22.88% vs 14.09%), among the one-dose, two-dose, and three-dose groups (14.51% vs 23.80% vs 38.18%), and among the groups with interval ≤ 1 month, 1-2 months, and ≥ 2 months (1.01% vs 8.44% vs 28.16%). There were significant differences in the neonatal weight between the vaccination and non-vaccination groups [3805.50 (3746.00-3863.50) vs 2970.00 (2500.00-3400.00)]. There were significant differences in the premature birth rate among the one-dose, two-dose, and three-dose groups (23.26% vs 34.59% vs 100.00%), and among the groups with interval ≤ 1 month, 1-2 months, and ≥ 2 months (15.79% vs 21.43% vs 37.00%). Conclusion: Pregnancy outcomes were not affected by taking the SARS-CoV-2 inactivated vaccine before FET, the number of doses, and the interval between doses. These findings provide evidence supporting the safety of administering the SARS-CoV-2 inactivated vaccine during pregnancy, which can be used as a guide for vaccinating patients undergoing ART.
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OBJECTIVE: To investigate the effects of chromosome polymorphism on the clinical outcomes of in vitro fertilization/embryo transfer (IVF/ET)-assisted reproductive technology. METHODS: The case data of 2740 patients treated between January 2018 and January 2019 were retrospectively analyzed. The patients were organized into two groups: a case group and a control group. In the case group (n = 81), one or both parents were characterized by chromosomal polymorphism; in the control group (n = 2659), both parents had normal chromosome karyotyping. The primary outcomes included clinical pregnancy rate (clinical pregnancy rate of fresh transfer cycles = number of clinical pregnancy cycles/number of fresh embryo transfer cycles × 100%) and live birth rate (live birth rate per fresh transfer cycles = number of live births/numbers of fresh embryo transfer cycles × 100%). The propensity score matching (PSM) method was used for statistical analysis. RESULTS: After PSM 1:2 matching for the patients in the two groups, 72 patients were successfully matched. The clinical pregnancy rate and live birth rate in the case group were lower than in the control group before PSM (clinical pregnancy rate: 33.30% case group vs. 46.60% control group, p = .020; live birth rate: 30.90% case group vs. 47.90% control group, p = .03). The differences were statistically significant (p < .05). The live birth rate in the case group was also significantly lower than in the control group after PSM (34.98% case group vs. 74.52% control group; p = .028). The correlation coefficient between clinical pregnancy and grouping (i.e. if there was a characteristic chromosome polymorphism) was -.045 (p = .02), while the correlation coefficient between live birth and grouping was -.046. CONCLUSION: Chromosome polymorphism is weakly negatively correlated with live birth in IVF/ET-assisted reproduction and can significantly reduce the live birth rate of patients.
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Transferencia de Embrión , Fertilización In Vitro , Embarazo , Femenino , Humanos , Estudios Retrospectivos , Fertilización In Vitro/efectos adversos , Transferencia de Embrión/efectos adversos , Índice de Embarazo , Embarazo Múltiple , Nacimiento Vivo , CromosomasRESUMEN
Cognitive deficit is a common comorbidity in temporal lobe epilepsy (TLE) and is not well controlled by current therapeutics. How epileptic seizure affects cognitive performance remains largely unclear. In this study we investigated the role of subicular seizure-activated neurons in cognitive impairment in TLE. A bipolar electrode was implanted into hippocampal CA3 in male mice for kindling stimulation and EEG recording; a special promoter with enhanced synaptic activity-responsive element (E-SARE) was used to label seizure-activated neurons in the subiculum; the activity of subicular seizure-activated neurons was manipulated using chemogenetic approach; cognitive function was assessed in object location memory (OLM) and novel object recognition (NOR) tasks. We showed that chemogenetic inhibition of subicular seizure-activated neurons (mainly CaMKIIα+ glutamatergic neurons) alleviated seizure generalization and improved cognitive performance, but inhibition of seizure-activated GABAergic interneurons had no effect on seizure and cognition. For comparison, inhibition of the whole subicular CaMKIIα+ neuron impaired cognitive function in naïve mice in basal condition. Notably, chemogenetic inhibition of subicular seizure-activated neurons enhanced the recruitment of cognition-responsive c-fos+ neurons via increasing neural excitability during cognition tasks. Our results demonstrate that subicular seizure-activated neurons contribute to cognitive impairment in TLE, suggesting seizure-activated neurons as the potential therapeutic target to alleviate cognitive impairment in TLE.
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Disfunción Cognitiva , Epilepsia del Lóbulo Temporal , Masculino , Ratones , Animales , Convulsiones , Neuronas , Epilepsia del Lóbulo Temporal/psicología , Hipocampo , CogniciónRESUMEN
Phototherapy is an emerging non-pharmacological treatment for depression, circadian rhythm disruptions, and neurodegeneration, as well as pain conditions including migraine and fibromyalgia. However, the mechanism of phototherapy-induced antinociception is not well understood. Here, using fiber photometry recordings of population-level neural activity combined with chemogenetics, we found that phototherapy elicits antinociception via regulation of the ventral lateral geniculate body (vLGN) located in the visual system. Specifically, both green and red lights caused an increase of c-fos in vLGN, with red light increased more. In vLGN, green light causes a large increase in glutamatergic neurons, whereas red light causes a large increase in GABAergic neurons. Green light preconditioning increases the sensitivity of glutamatergic neurons to noxious stimuli in vLGN of PSL mice. Green light produces antinociception by activating glutamatergic neurons in vLGN, and red light promotes nociception by activating GABAergic neurons in vLGN. Together, these results demonstrate that different colors of light exert different pain modulation effects by regulating glutamatergic and GABAergic subpopulations in the vLGN. This may provide potential new therapeutic strategies and new therapeutic targets for the precise clinical treatment of neuropathic pain.
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Neuralgia , Nocicepción , Ratones , Animales , Nocicepción/fisiología , Neuronas GABAérgicas , Cuerpos Geniculados/fisiología , Fototerapia , Neuralgia/terapiaRESUMEN
OBJECTIVE: To investigate the correlation between methylenetetrahydrofolate reductase (MTHFR) gene-specific methylation and recurrent spontaneous abortion (RSA). METHODS: A total of 50 RSA patients who visited our hospital were recruited in the study group; 50 multiparous women who underwent physical examinations during the same period were enrolled in the control group. The levels of homocysteine, folic acid, and vitamin B12 and their MTHFR gene polymorphism and specific methylation were measured in both groups. The Logistic regression equation was used to analyze the correlation between MTHFR gene-specific methylation and RSA. RESULTS: The methylated allele MM was not found in the control group, and the frequency in the study group was 1.19%. The frequency of the MU genotype in the study group 32.93% was higher than that in the control group 12.45%. The frequency of methylated alleles of CC and CT genotypes carrying MTHFR C677T polymorphism in the study group was higher than that in the control group (P < 0.05). There was no significant difference in the TT genotype between the two groups (P > 0.05). Multivariate Logistic regression analysis exhibited that patients with methylated alleles of CC genotype had a risk of RSA increased by 1.167 times, and the risk increased by 2.500 times in patients with methylated alleles of CT genotype (P < 0.05). 83.33% of RSA patients carrying methylated alleles affected hyperhomocysteinemia. In patients with elevated homocysteine levels, the risk of RSA caused by methylated allele was significantly increased by 7.321 times. CONCLUSION: MTHFR gene-specific methylation can significantly increase the risk of RSA.
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PURPOSE: Acute kidney injury (AKI) induced by renal ischaemia/reperfusion (I/R) during renal transplantation has been reported to be linked to the regulation of SIRT2, one of the members of SIRTUINS family. Current work is attempted to explore the influence and mechanism of SIRT7 in renal cell apoptosis controlled by miR-152-3p during renal I/R injury. METHODS: Three databases were used to select the miRNAs regulating the expression of SIRT7. Overexpression and inhibition of miR-152-3p and Luciferase assay were employed to certify the modulation of miR-152-3p to SIRT7 in cells. RT-qPCR assay was used to measure the mRNA levels. Western blot assay was employed to determine the expression of proteins. TUNEL assay and Flow Cytometry were conducted to analyze cell apoptosis. RESULTS: SIRT7 expression decreased in tissues of AKI patients and rats underwent renal I/R, which was associated with enhanced impairment of renal function. SIRT7 downregulation was attributed to the direct inhibition by miR-152-3p due to binding and inhibiting its seed sequence in 3'-UTR of SIRT7 mRNA. Consequently, the upregulation of miR-152-3p led to an inhibition of SIRT7 expression, an increase in expression of extrinsic apoptosis molecules containing FOXO3a, Bim, and caspase3, and apoptotic renal cells; while miR-152-3p inhibition abolished these phenotypes. CONCLUSION: SIRT7 downregulation by miR-152-3p is a leading cause of renal cell apoptosis and functional impairment induced by renal I/R. Inhibition of miR-152-3p to restore SIRT7 expression can be a promising strategy against renal I/R injury.
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Lesión Renal Aguda , MicroARNs , Daño por Reperfusión , Sirtuinas , Ratas , Animales , Daño por Reperfusión/complicaciones , Daño por Reperfusión/genética , Daño por Reperfusión/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Riñón/metabolismo , Apoptosis/genética , Lesión Renal Aguda/genética , ARN Mensajero , Sirtuinas/genéticaRESUMEN
BACKGROUND: Rheumatoid arthritis patients usually suffer from arthritic chronic pain. However, due to an incomplete understanding of the mechanisms underlying autoimmune disorders, the management of arthritic pain is unsatisfactory. Here, we investigated the analgesic effect and underlying mechanism of the natural flavonoid naringenin (NAR) in collagen-induced arthritis (CIA) pain. METHODS: NAR was injected (i.p.) once per day for 42 days after initial immunization, and rats were sacrificed on the 28th (the 21st day after final immunization, PID 21) and 42nd days (PID 35). The inflammatory factors, central sensitization indicators, and CRMP2 phosphorylation, as well as the anti-rheumatoid activity and analgesic effect of NAR, were further investigated. RESULTS: We found that NAR decreased the arthritis score and paw swelling, as well as the mechanical and thermal pain. The immunofluorescence results also showed a dose dependent effect of NAR on reducing the expressions of spinal cFos, IBA-1, and GFAP on the 28th (PID 21) and 42nd day (PID 35). NAR decreased the phosphorylation of CRMP2 S522 and the expression of the kinase CDK5 in the spinal dorsal horn, but pCRMP2 Y479 was unchanged. In addition, CRMP2 was co-localized with NEUN, but not IBA-1 or GFAP, indicating the involvement of neural CRMP2 phosphorylation in CIA-related pain. Finally, CRMP2 S522 phosphorylation selective inhibitor (S)-lacosamide also alleviated arthritic pain. CONCLUSIONS: Taken together, our results demonstrate that NAR alleviates inflammation and chronic pain in CIA model, which might be related to its inhibition of neuronal CRMP2 S522 phosphorylation, potentially mitigating the central sensitization. Our study provide evidence for the potential use of NAR as non-opioid-dependent analgesia in arthritic pain.
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Artritis Experimental , Artritis Reumatoide , Dolor Crónico , Ratas , Animales , Fosforilación , Flavonoides/farmacología , Artralgia , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/metabolismo , AnalgésicosRESUMEN
OBJECTIVE: This study aimed to investigate the duration of progesterone (P) therapy on clinical pregnancy rates as measured by the window of implantation (WOI) in the first cycle of frozen embryo transplantation. METHODS: The study compared the pregnancy rates between 345 cleavage stage transfers and 348 blastocyte transfers of frozen embryos with modified natural cycles in patients from July 1, 2020, to November 30, 2020. Four different P durations were analyzed in the cleavage stage embryo transfer group, i.e., two, three, four, and five days. Five different P durations were analyzed in the blastocyst transfer group, i.e., three, four, five, six, and seven days. RESULTS: The baseline demographics and clinical characteristics of the cleavage stage embryos and blastocyst transfer groups were not comparable. The clinical pregnancy rates following the cleavage stage embryo transfer after two, three, four, and five-day P administration were 45.71%, 44.60%, 38.40%, and 30.43%, respectively (the difference among the subgroups was not significant). Following the blastocyst transfer, the clinical pregnancy rates after three, four, five, six, and seven-day P administration were 50.65%, 63.51%, 60.00%, 54.55%, and 61.54%, respectively (the difference among the subgroups was not significant). In contrast, these two transfer groups showed significantly different clinical pregnancy rates following four and five-day P exposure (P < 0.05). CONCLUSION: For cleavage-stage embryo transfer, the most effective WOI was found between days two and five of P administration. The effective WOI for blastocyst transfer was observed between days three and seven of P administrations.
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Implantación del Embrión , Transferencia de Embrión , Femenino , Humanos , Embarazo , Índice de Embarazo , Estudios RetrospectivosRESUMEN
Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are the production of renal ischemia/reperfusion (I/R). The current study is to elucidate a mechanism of SIRT2 tyrosine nitration to accelerate the cell apoptosis induced by peroxynitrite (ONOOâ¾), the most reactive and deleterious RNS type in renal ischemia/reperfusion (I/R) injury. Our results demonstrate that there is a significant enhancement of the 3-nitrotyrosine levels in renal tissues of Acute Kidney Injury (AKI) patients and rats that underwent renal I/R, and a positive correlation between the 3-nitrotyrosine level and renal function impairment, indicative of an accumulation of peroxynitrite. Notably, peroxynitrite-evoked nitration of SIRT2 destroyed its enzymatic activity and the capability to deacetylate FOXO3a, and enhanced expression of Bim and caspase3, facilitating renal cell apoptosis in renal ischemia/reperfusion and SIN-1(peroxynitrite donor) treatment in vitro, and these effects were reversed by FeTMPyP, a peroxynitrite decomposition scavenger. Importantly, we identified that the tyrosine 86 is responsible for SIRT2 nitration and inactivation using site-mutation assay and Mass Spectrography analysis. Altogether, these findings point to a novel protective mechanism that an inhibition of SIRT2 tyrosine nitration can be a promising strategy to prevent ischemic renal diseases involving AKI.
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Lesión Renal Aguda , Daño por Reperfusión , Animales , Humanos , Isquemia , Riñón/fisiología , Ácido Peroxinitroso/farmacología , Ratas , Daño por Reperfusión/metabolismo , Sirtuina 2 , TirosinaRESUMEN
OBJECTIVE: To select potential molecules that can target viral spike proteins, which may potentially interrupt the interaction between the human angiotension-converting enzyme 2 (ACE2) receptor and viral spike protein by virtual screening. METHODS: The three-dimensional (3D)-coordinate file of the receptor-binding domain (RBD)-ACE2 complex for searching a suitable docking pocket was firstly downloaded and prepared. Secondly, approximately 15,000 molecular candidates were prepared, including US Food and Drug Administration (FDA)-approved drugs from DrugBank and natural compounds from Traditional Chinese Medicine Systems Pharmacology (TCMSP), for the docking process. Then, virtual screening was performed and the binding energy in Autodock Vina was calculated. Finally, the top 20 molecules with high binding energy and their Chinese medicine (CM) herb sources were listed in this paper. RESULTS: It was found that digitoxin, a cardiac glycoside in DrugBank and bisindigotin in TCMSP had the highest docking scores. Interestingly, two of the CM herbs containing the natural compounds that had relatively high binding scores, Forsythiae fructus and Isatidis radix, are components of Lianhua Qingwen (), a CM formula reportedly exerting activity against severe acute respiratory syndrome (SARS)-Cov-2. Moreover, raltegravir, an HIV integrase inhibitor, was found to have a relatively high binding score. CONCLUSIONS: A class of compounds, which are from FDA-approved drugs and CM natural compounds, that had high binding energy with RBD of the viral spike protein. Our work provides potential candidates for other researchers to identify inhibitors to prevent SARS-CoV-2 infection, and highlights the importance of CM and integrative application of CM and Western medicine on treating COVID-19.
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Infecciones por Coronavirus/tratamiento farmacológico , Reposicionamiento de Medicamentos/métodos , Medicamentos Herbarios Chinos/farmacología , Glicoproteínas/efectos de los fármacos , Imagenología Tridimensional , Simulación del Acoplamiento Molecular/métodos , Neumonía Viral/tratamiento farmacológico , COVID-19 , China , Simulación por Computador , Infecciones por Coronavirus/diagnóstico , Glicoproteínas/metabolismo , Humanos , Tamizaje Masivo/métodos , Pandemias , Peptidil-Dipeptidasa A/efectos de los fármacos , Neumonía Viral/diagnóstico , Unión Proteica , Estados Unidos , United States Food and Drug AdministrationRESUMEN
A continuous flow reactor (TCFR) with 10 compartments was used to treat domestic sewage. The anaerobic compartments of TCFR were kept at 3. The anoxic compartments of TCFR were reduced from 2 to 0. Therefore, the aerobic compartments of TCFR were increased gradually from 5 to 7. The aerobic compartments were set to continual aeration in Run1 and intermittent aeration from Run2 to Run4. The aeration/non-aeration ratios were 40 min/20 min,40 min/30 min, and 40 min/40 min, respectively. The nitrification liquid reflux ratios were reduced gradually from 150% to 0%. When the average influent concentrations of COD, NH4+-N, TN, and PO43--P were 259.34, 60.26, 64.42, and 6.10 mg·L-1, respectively, the corresponding effluent concentrations were 26.40, 1.03, 5.84, and 0.3 mg·L-1, respectively in Run4. The nitrogen removal amounts increased gradually from 192.30 mg·h-1 in Run1 to 244.00 mg·h-1 in Run4, and the corresponding removal rates increased from 65.40% to 95.30%. The activity of denitrifying phosphorus accumulating organisms (DPAOs) and phosphorus accumulating organisms (PAOs) increased from 36.05% and 38.20% in Run1 to 140.50% and 133.40% in Run4, respectively. Simultaneous nitrification and denitrifying phosphorus removal was achieved in TCFR by adopting intermittent aeration, which provided a reference for the reformation of sewage treatment plants.
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Reactores Biológicos , Desnitrificación , Nitrificación , Nitrógeno/aislamiento & purificación , Fósforo/aislamiento & purificación , Eliminación de Residuos Líquidos/métodos , Aguas del AlcantarilladoAsunto(s)
Rotura Prematura de Membranas Fetales , Trombina , Amnios , Femenino , Humanos , Recién Nacido , EmbarazoRESUMEN
Intrauterine adhesion (IUA) is now recognized as one of the most common diseases in reproductive-age women. Metformin, a well-known frontline oral antidiabetic drug, has been found effective in numerous different diseases. The aim of this study was to determine the effect of metformin on reducing adhesions in an animal model of IUA. Sprague-Dawley rats were randomized into 4 groups: sham operation, control, metformin-treated for 7 days, and metformin-treated for 14 days. To establish the IUA model, mechanical injury to the endometria of rats was induced with a mini curette. Metformin was injected intraperitoneally after surgery. A significant amelioration in both the number of glands and the fibrotic area, compared to those of the control group, was detected 14 days after metformin intervention. The expression levels of antigen KI-67 and vascular endothelial growth factor were increased at 7 and 14 days after treatment. However, the transforming growth factor-ß expression was decreased at 14 days after treatment. Endoplasmic reticulum stress-related apoptosis proteins (glucose-regulated protein 78, caspase-12, and CCAAT/enhancer binding protein (EBP) homologous protein) were downregulated after metformin treatment. Moreover, we determined that the effect of metformin was related to the inhibition of endoplasmic reticulum stress-induced apoptosis via the Phosphatidylinositol 3 kinase (PI3K)/Protein kinase B (AKT) and Extracellular regulated protein kinases1/2 pathways. In conclusion, metformin can attenuate the adhesion and promote the regeneration of the endometrium of the IUA rat, and metformin may serve as a novel therapeutic strategy for IUA patients.
Asunto(s)
Apoptosis/efectos de los fármacos , Endometrio/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Ginatresia/prevención & control , Metformina/administración & dosificación , Regeneración/efectos de los fármacos , Animales , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Endometrio/metabolismo , Endometrio/patología , Femenino , Fibrosis/prevención & control , Ginatresia/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratas Sprague-DawleyRESUMEN
The abuse of amphetamine-type stimulants (ATS) has become a global public health issue in recent years, these new-type drugs can cause addiction and serious cognitive impairment. However, there are no effective methods for the prevention and treatment of ATS addiction at present. Repetitive transcranial magnetic stimulation (rTMS) is a painless and non-invasive new therapeutic approach that has been used for the treatment of depression and other neuropsychiatric disorders, but whether it can be used to treat drug addiction is unclear. In the present study, we investigated the possible effects of rTMS on methamphetamine(METH)-induced conditioned place preference (CPP). High-frequency (10â¯Hz) and low-frequency stimulation patterns (1â¯Hz) were applied to test the effect of rTMS on METH-induced CPP. The results showed that low-frequency but not high-frequency rTMS could block METH-CPP, accompanied with a downregulation of gamma-aminobutyric acid type B receptor subunit 1 (GABABR1) expression in rat dorsolateral striatum. These results suggested that low-frequency rTMS could effectively inhibit the development of METH addiction and shed light on the rTMS as a potential approach for the prevention of drug addiction.