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1.
Pharm Biol ; 59(1): 1594-1606, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34808067

RESUMO

CONTEXT: Xiaoyaosan decoction (XYS), a classical Traditional Chinese Medicine (TCM) formula is used to treat liver fibrosis in clinics. OBJECTIVE: This study explores defined compound combinations from XYS decoction to treat liver fibrosis. MATERIALS AND METHODS: Network pharmacology combined with transcriptomics analysis was used to analyze the XYS decoction and liver depression and spleen deficiency syndrome liver fibrosis. From the constructed XYS-Syndrome-liver fibrosis network, the top 10 active formulas were developed by topological analysis according to network stability. The most active formula was determined by in vitro study. The anti-fibrosis effect was evaluated by in vitro and in vivo studies. RESULTS: According to the network XYS-Syndrome-liver fibrosis network, 8 key compounds and 255 combinations were predicted from in XYS. Luteolin, licochalcone A, aloe-emodin and acacetin formula (LLAAF) had a synergistic effect on the proliferation inhibition of hepatic stellate cells compared to individual compounds alone. The treatment of XYS and LLAAF showed a similar anti-liver fibrotic effect that reduced histopathological changes of liver fibrosis, Hyp content and levels of α-SMA and collagen I in CCl4-induced liver fibrosis in rats. Transcriptomics analysis revealed LLAAF regulated PI3K-Akt, AMPK, FoxO, Jak-STAT3, P53, cell cycle, focal adhesion, and PPAR signalling. Furthermore, LLAAF was confirmed to regulate Jak-STAT and PI3K-Akt-FoxO signalling in vitro and in vivo. CONCLUSIONS: This study developed a novel anti-liver formula LLAAF from XYS, and demonstrated its anti-liver fibrotic activity which may be involved in the regulation of Jak-STAT and PI3K-Akt-FoxO signalling.

2.
Pak J Pharm Sci ; 34(3): 957-961, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34602419

RESUMO

The present study was performed in order to investigate the safety and efficacy of different vasoactive drugs combined with enteral nutrition in terms of treating elderly patients with sepsis. A total of 75 elderly patients with sepsis treated with enteral nutrition in our hospital were randomly divided into three groups: group A (n = 25), group B (n = 25) and group C (n = 25). The three groups were treated with dopamine, dobutamine and norepinephrine respectively. One week after treatment, the therapeutic effects of the three groups were compared, the vascular elastic indexes, hemodynamic indexes and levels of inflammatory factors of the three groups were measured. After treatment, the clinical effective rate of group C was evidently higher than that of group A and group B. The vascular elasticity coefficient and stiffness coefficient in group C were significantly lower than those in group A and group B, and the arterial compliance in group C was significantly higher than that in group A and group B (P < 0.05). The levels of MAP and PVRI in group C were significantly higher than those in group A and B, and the levels of CI, CVP and HR in group C were significantly lower than those in group A and group B (P < 0.05). Norepinephrine elicited greater effects in terms of improving hemodynamic indexes, vascular elasticity and reducing the level of inflammatory factors compared with dopamine and dobutamine in elderly patients harboring sepsis.

3.
World J Gastroenterol ; 27(36): 6064-6078, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34629820

RESUMO

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer and the second most common cause of cancer-related death worldwide. The 5-year survival rate of patients with early-stage CRC could reach 90%, but it is very low in patients with advanced-stage CRC. Recent studies have shown that circular RNAs play important roles in regulating the migration and invasion of CRC cells. AIM: To elucidate the role of circRNA_0084927 (circ_0084927) in the migration and invasion of CRC cells and its underlying mechanism. METHODS: Clinical tissue samples and cells were collected, and the expression of circ_0084927 was detected by quantitative polymerase chain reaction (qPCR). The diagnostic performance of circ_0084927 was assessed by receiver operating characteristic curve analysis. The role of circ_0084927 in CRC cell proliferation, migration, and invasion was determined using cell counting kit-8 assay, wound healing assay, and transwell assay, respectively. The regulatory relationship among circ_0084927, miRNA-20b-3p (miR-20b-3p), and glutathione S-transferase mu 5 (GSTM5) was identified using databases, luciferase reporter assay, qPCR, and Western blot analysis. AKT-mTOR signaling was also verified after circ_0084927 knockdown or miR-20b-3p mimic treatment. RESULTS: The expression of circ_0084927 was significantly increased in CRC tissues and cells, and it was higher in advanced-stage CRC compared with early-stage CRC. The area under the curve (AUC) of circ_0084927 was 0.806 [95% confidence interval (CI): 0.683-0.896]. In addition, the AUC was 0.874 (95%CI: 0.738-0.956) in patients with advanced-stage CRC and 0.713 (95%CI: 0.555-0.840) in those with early-stage CRC. Knockdown of circ_0084927 inhibited the migration and invasion of HCT116 cells. Moreover, circ_0084927 was found to act as a sponge of miR-20b-3p. MiR-20b-3p activation reduced the circ_0084927 level, whereas miR-20b-3p inhibition increased the circ_0084927 level. But the effect was not found after circ_0084927 mutation. In addition, miR-20b-3p expression in CRC patients was also reduced and negatively correlated with circ_0084927 expression. The function of circ_0084927 in HCT116 cells with circ_0084927 knockdown was rescued by miR-20b-3p. Moreover, GSTM5 expression was significantly decreased after overexpressing miR-20b-3p or inhibiting circ_0084927, but its expression was rescued when circ_0084927 and miR-20b-3p were both inhibited. Finally, AKT-mTOR signaling was markedly regulated by circ_0084927 and miR-20b-3p. CONCLUSION: The expression of circ_0084927 is significantly increased in CRC and higher in advanced-stage CRC than in early-stage CRC. Moreover, circ_0084927 potentially regulates CRC cell migration and invasion via the miR-20b-3p/GSTM5/ AKT/mTOR pathway.


Assuntos
Neoplasias Colorretais , MicroRNAs , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Glutationa Transferase , Humanos , MicroRNAs/genética , RNA Circular
4.
J Assist Reprod Genet ; 38(11): 2965-2974, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34554361

RESUMO

OBJECTIVES: To examine the association between modifiable lifestyle factors and the main semen parameter values, the number of qualified sperm donors, and to provide some sensible guidance for sperm donors. METHODS: Healthy men screened as potential sperm donors were recruited in the Hunan Province Human Sperm Bank of China from March 2019 to December 2019. Participants were invited to complete interviewer-assisted questionnaires on eleven items of information. Univariate and multivariate analyses were conducted to analyze which lifestyle factors collected by the questionnaire had an impact on the eligibility and main semen parameters of sperm donors. RESULTS: The eligibility of men as sperm donors was strongly influenced by the duration of abstinence (P = 0.002). The rate of eligibility sperm donors increased significantly with the number of days of abstinence. In addition, semen volume increased with abstinence time (P = 0.000). Exercise frequency (P = 0.025) and abstinence time (P = 0.000) were positively correlated with sperm concentration, and masturbation frequency was negatively correlated with sperm concentration (P = 0.013). Progressive sperm motility was significantly affected by abstinence time (P = 0.000) and bedtime (P = 0.047). CONCLUSIONS: Abstinence time was highly associated with semen parameters and donor qualification. Increase the abstinence time before donation may be meaningful in improving the proportion of eligible sperm donors.

5.
Zhongguo Zhen Jiu ; 41(7): 789-91, 2021 Jul 12.
Artigo em Chinês | MEDLINE | ID: mdl-34259413

RESUMO

Professor ZHENG Liang believes that the main pathogenesis of postoperative facial paralysis is related to the retarded circulation of qi and blood and malnutrition of tendons and vessels in local area because of local retention of "stasis" after surgical trauma. In treatment of postoperative facial paralysis with acupotomy, the abnormal facial structure after operation should be considered specially. The region where acupotomy is exerted is determined by taking surgical scar as the center so that the local adhesion can be released and separated. In treatment, the knife needle should be as fine as possible and the attention be paid to the direction of needle insertion and the release amplitude. The frequency of acupotomy should be once per week.


Assuntos
Terapia por Acupuntura , Paralisia Facial , Paralisia Facial/etiologia , Paralisia Facial/terapia , Humanos , Terapias Mente-Corpo , Período Pós-Operatório , Tendões
6.
Front Immunol ; 12: 679090, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34054869

RESUMO

Immune checkpoint inhibitors (ICIs) have become a promising area of research for cancer treatment. In addition to the well-known ICIs targeting PD-1/PD-L1, HLA-G/ILT-2/-4 is relatively new immune checkpoint that has been evaluated in early clinical trials in patients with advanced solid tumors. In this study, the expression of HLA-G (n=157), ILT-2/4 (n=82), and PD-L1 (n=70) in epithelial cell adhesion molecule (EpCAM)-positive colorectal cancer (CRC) cells was analyzed by multicolor flow cytometry, and the prognostic significance of these molecules was evaluated. In EpCAM+ CRC cells, the median percentages of HLA-G, ILT-2, ILT-4, and PD-L1 were 14.90%, 67.70%, 8.55% and 80.30%, respectively. In addition, a positive correlation was observed between them (all p<0.001). Higher levels of these immune checkpoint proteins are associated with lymph node metastasis. In addition to the AJCC stage (p=0.001), Kaplan-Meier survival analysis showed that higher levels of HLA-G (p=0.041), ILT-2 (p=0.060), ILT-4 (p<0.001), PD-L1 (p=0.012), HLA-GILT4 (p<0.001) and ILT-2ILT-4 (p<0.001) were significantly associated with shorter survival of CRC patients. When CRC patients were stratified by early and advanced AJCC stages, HLA-G levels were only related to the survival among CRC patients with early disease stage (p=0.024), while ILT-4 levels were significant for both CRC patients with early (p=0.001) and advanced (p=0.020) disease stages. Multivariate cox regression analysis revealed that advanced AJCC stage (HR=2.435; p=0.005) and higher ILT-4 levels (HR=2.198; p=0.063) were independent risk factors for poor outcomes in patients with CRC. In summary, among the immune checkpoints, HLA-G/ILT-2/4 and PD-L1, ILT-4 is the most significant prognostic indicator of CRC. This finding indicated that a combination of immunotherapy strategies, such as ILT-4 blockade, could improve the clinical outcomes in patients with cancer. Moreover, multicolor flow cytometry can be employed as a reliable and efficient, alternative to immunohistochemistry, for evaluating the immune checkpoint proteins expressed in tumor lesions.


Assuntos
Antígenos CD/metabolismo , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/metabolismo , Antígenos HLA-G/imunologia , Receptor B1 de Leucócitos Semelhante a Imunoglobulina/metabolismo , Glicoproteínas de Membrana/metabolismo , Receptores Imunológicos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/genética , Antígeno B7-H1/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/mortalidade , Suscetibilidade a Doenças , Feminino , Expressão Gênica , Antígenos HLA-G/genética , Humanos , Proteínas de Checkpoint Imunológico/genética , Proteínas de Checkpoint Imunológico/metabolismo , Imunofenotipagem , Estimativa de Kaplan-Meier , Receptor B1 de Leucócitos Semelhante a Imunoglobulina/genética , Masculino , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Receptores Imunológicos/genética
7.
Cryobiology ; 100: 58-62, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33831370

RESUMO

Techniques for the cryopreservation of epididymal sperm was are widely used in clinical practice. However, given the unique characteristics of sperm from patients with obstructive azoospermia, epididymal sperm cryopreservation is more difficult because of low count and weak motility; therefore, conventional methods of sperm cryopreservation may not result in the best outcomes. We used the micro-straw method to store small quantities of sperm obtained from patients with severe oligozoospermia or azoospermia and achieved successful deliveries in the previous study. This retrospective study of ICSI cycles included the first ICSI cycles of fresh or frozen/thawed epididymal sperm that were performed in patients suffering from obstructive azoospermia who were admitted to the CITIC-Xiangya Hospital of Reproduction and Genetics of China from June 1, 2015 to June 31, 2019. A total of 2441 patients with obstructive azoospermia were divided according to the use of fresh (n = 2342) or frozen/thawed (n = 99) epididymal sperm. The results showed that the fertilisation rate was higher with fresh epididymal sperm than that with frozen/thawed epididymal sperm (85.14% vs. 79.26%, respectively; p = 0.000). However, the rates of embryo cleavage, high-quality embryos, clinical pregnancy, miscarriage, singletons and birth defect were similar between fresh and frozen/thawed epididymal sperm (98.28% vs. 99.13%, 60.34% vs. 57.29%, 67.90% vs. 70.51%, 8.12% vs. 10.91%, 57.76% vs. 49.09%, 1.59% vs. 1.45%respectively; p = 0.088, 0.109, 0.628, 0.462,0.203 and 0.686). In addition, the short-term cryostorage of small quantities of epididymal sperm did not affect clinical outcomes. The results indicated that in cases of obstructive azoospermia, cryostorage of small quantities epididymal sperm is a reliable option.


Assuntos
Azoospermia , Oligospermia , China , Criopreservação/métodos , Feminino , Humanos , Masculino , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Espermatozoides , Testículo
8.
Front Pharmacol ; 12: 524663, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33828479

RESUMO

There is a lack of effective therapeutic drugs in patients with postoperative colorectal cancer (PCRC). This study aimed to investigate the therapeutic effect and mechanisms of Bushen-Jianpi-Jiedu decoction (BSJPJDD) combined with chemotherapeutic drugs (oxaliplatin) on PCRC with liver and kidney yin deficiency and spleen deficiency syndrome (LKYD-SDS) through the therapeutic evaluation of clinical therapy and the integrative analysis of network pharmacology, RNA-seq and label-free data, and experiment verification in vitro. In clinical therapy, the median progression-free survival (PFS) and Karnofsky performance score (KPS) were increased in PCRC patients by the aqueous extract of BSJPJDD combined with oxaliplatin treatment for three months, compared to oxaliplatin alone (p < 0.05). The integrative analysis showed that 559 differentially expressed genes (DEGs) and 11 differentially expressed proteins (DEPs) were regulated by BSJPJDD, among which seven bioactive compounds through 39 potential targets were involved in the regulation of multiple signaling pathways including MAPK, PI3K-Akt, and HIF-1, etc. In the experimental verification, an ELISA assay showed that plasma ZEB2, CAT, and KRT78 were decreased, and IL-1Α, CD5L, FBLN5, EGF, and KRT78 were increased in comparison to the above (p < 0.05). Furthermore, the SW620 cell viability was inhibited and the expressions of MAPK and the p-ERK/ERK ratio were significantly downregulated by the aqueous extract of BSJPJDD combined with oxaliplatin treatment, compared with oxaliplatin treatment alone (p < 0.05). These data suggested that BSJPJDD combined with oxaliplatin prolongs the survival and improves Karnofsky performance status of PCRC patients with LKYD-SDS, and may be associated with the regulation of multiple signaling pathways.

9.
Angew Chem Int Ed Engl ; 60(25): 14068-14075, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-33793030

RESUMO

Reductive carboxylation of organo (pseudo)halides with CO2 is a powerful method to provide carboxylic acids quickly. Notably, the catalytic reductive carbo-carboxylation of unsaturated hydrocarbons via CO2 fixation is a highly challenging but desirable approach for structurally diverse carboxylic acids. There are only a few reports and no examples of alkenes via transition metal catalysis. We report the first asymmetric reductive carbo-carboxylation of alkenes with CO2 via nickel catalysis. A variety of aryl (pseudo)halides, such as aryl bromides, aryl triflates and inert aryl chlorides of particular note, undergo the reaction smoothly to give important oxindole-3-acetic acid derivatives bearing a C3-quaternary stereocenter. This transformation features mild reaction conditions, wide substrate scope, facile scalability, good to excellent chemo-, regio- and enantioselectivities. The method highlights the formal synthesis of (-)-Esermethole, (-)-Physostigmine and (-)-Physovenine, and the total synthesis of (-)-Debromoflustramide B, (-)-Debromoflustramine B and (+)-Coixspirolactam A; thereby, opening an avenue for the total synthesis of chiral natural products with CO2 .

10.
Molecules ; 26(8)2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33921192

RESUMO

Triple-negative breast cancer (TNBC) is a refractory type of breast cancer that does not yet have clinically effective drugs. The aim of this study is to investigate the synergistic effects and mechanisms of resveratrol combined with cisplatin on human breast cancer MDA-MB-231 (MDA231) cell viability, migration, and invasion in vivo and in vitro. In vitro, MTS assays showed that resveratrol combined with cisplatin inhibits cell viability as a concentration-dependent manner, and produced synergistic effects (CI < 1). Transwell assay showed that the combined treatment inhibits TGF-ß1-induced cell migration and invasion. Immunofluorescence assays confirmed that resveratrol upregulated E-cadherin expression and downregulated vimentin expression. Western blot assay demonstrated that resveratrol combined with cisplatin significantly reduced the expression of fibronectin, vimentin, P-AKT, P-PI3K, P-JNK, P-ERK, Sma2, and Smad3 induced by TGF-ß1 (p < 0.05), and increased the expression of E-cadherin (p < 0.05), respectively. In vivo, resveratrol enhanced tumor growth inhibition and reduced body weight loss and kidney function impairment by cisplatin in MDA231 xenografts, and significantly reduced the expressions of P-AKT, P-PI3K, Smad2, Smad3, P-JNK, P-ERK, and NF-κB in tumor tissues (p < 0.05). These results indicated that resveratrol combined with cisplatin inhibits the viability of breast cancer MDA231 cells synergistically, and inhibits MDA231 cells invasion and migration through Epithelial-mesenchymal transition (EMT) approach, and resveratrol enhanced anti-tumor effect and reduced side of cisplatin in MDA231 xenografts. The mechanism may be involved in the regulations of PI3K/AKT, JNK, ERK and NF-κB expressions.


Assuntos
Movimento Celular/efeitos dos fármacos , Cisplatino/farmacologia , Resveratrol/farmacologia , Neoplasias de Mama Triplo Negativas/patologia , Animais , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Humanos , Camundongos Endogâmicos BALB C , Invasividade Neoplásica , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta1/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Asian J Androl ; 23(4): 421-428, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33533739

RESUMO

Sperm morphology was once believed as one of the most predictive indicators of pregnancy outcome in assisted reproductive technology (ART). However, the impact of teratozoospermia on in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcomes and its offspring remains inconclusive. In order to evaluate the influence of teratozoospermia on pregnancy outcome and newborn status after IVF and ICSI, a retrospective study was conducted. This was a matched case-control study that included 2202 IVF cycles and 2574 ICSI cycles and was conducted at the Reproductive and Genetic Hospital of CITIC-Xiangya in Changsha, China, from June 2013 to June 2018. Patients were divided into two groups based on sperm morphology: teratozoospermia and normal sperm group. The pregnancy outcome and newborn outcome were analyzed. The results indicated that couples with teratozoospermia had a significantly lower optimal embryo rate compared to those with normal sperm morphology in IVF (P = 0.007), while there were no statistically significant differences between the two groups in terms of the fertilization rate, cleavage rate, implantation rate, and pregnancy rate (all P > 0.05). Additionally, teratozoospermia was associated with lower infant birth weight in multiple births after IVF. With regard to ICSI, there was no significant difference in both pregnancy outcome and newborn outcome between the teratozoospermia and normal groups (both P > 0.05). Furthermore, no increase in the risk of birth defects occurred in the teratozoospermia group after IVF/ICSI. Consequently, we believe that teratozoospermia has limited predictive value for pregnancy outcomes in IVF/ICSI, and has little impact on the resulting offspring if multiple pregnancy is avoided.

12.
Reprod Biomed Online ; 42(3): 589-594, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33384268

RESUMO

RESEARCH QUESTION: What are the risks associated with cryopreserved semen collected during and after the coronavirus disease 2019 (COVID-19) pandemic wave in Wuhan, China? DESIGN: Retrospective cohort study involving young adult men who were qualified sperm donors at the Hunan Province Human Sperm Bank (China) during the pandemic wave (1 January 2020 to 30 January 2020) and after the wave and return to work (7 April 2020 to 30 May 30 2020). One hundred paired semen and blood specimens from 100 donors were included. One-step single-tube nested quantitative real-time polymerase chain reaction (OSN-qRT-PCR) was used to detect SARS-CoV-2. Moreover, to control the unacceptable risk of false-negative results, a second round of screening was performed with pooled RNA from negative semen samples using crystal digital PCR (cd-PCR). RESULTS: For individual blood and semen samples, the target genes, namely the nucleocapsid protein (N) and open reading frame (ORF-1ab) genes, tested negative in all of the 100 paired samples. Further, as per cd-PCR results, there were >20,000 droplets per well in the RNA for each combined sample and no positive droplets were present for either of the aforementioned target genes. A total of 100 paired semen and blood samples from these two groups tested negative for SARS-CoV-2. CONCLUSIONS: Cryopreserved semen at the Hunan Province Human Sperm Bank during and after the COVID-19 pandemic wave was free of SARS-CoV-2 and was judged safe for external use in the future.


Assuntos
COVID-19 , Pandemias , China/epidemiologia , Humanos , Masculino , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , SARS-CoV-2 , Sêmen , Bancos de Esperma , Espermatozoides , Adulto Jovem
13.
Exp Ther Med ; 21(2): 156, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33456523

RESUMO

The present study aimed to compare the efficacy and safety of dexmedetomidine and midazolam in patients that are critically ill. Full text articles reporting the clinical effects and complications of dexmedetomidine and midazolam were retrieved from multiple databases. Review Manager 5.0 was adopted for meta-analysis, sensitivity and bias analysis. Finally, a total of 1,379 patients from 8 studies, which met the eligibility criteria, were included. The meta-analysis suggested that the length of stay at the intensive care unit [mean absolute difference (MD)=-1.80; 95% confidence interval (CI), -2.13, -1.48; P<0.00001; P-value for heterogeneity=0.41; I²=3%], time to extubation (MD=-2.18; 95% CI, -2.66, -1.69; P<0.00001; P-value for heterogeneity=0.84; I²=0%) and delirium (MD=0.46; 95% CI, 0.37, 0.57; P<0.00001; P-value for heterogeneity=0.65; I²=0%) was higher following midazolam treatment compared with dexmedetomidine, while bradycardia [odds ratio (OR)=5.03; 95% CI, 3.86, 6.57; P<0.00001; P-value for heterogeneity=0.13; I²=38%] was higher in dexmedetomidine treated patients compared with midazolam. However, no difference was observed in the incidence of hypotension (OR=0.88; 95% CI, 0.70, 1.10; P=0.26; P-value for heterogeneity=0.99; I²=0%) and mortality (OR=0.96; 95% CI, 0.74, 1.25; P=0.77; P-value for heterogeneity=0.99; I²=0%). Taking clinical effects and safety into account, the present study suggested dexmedetomidine to be the preferred option of anesthesia for patients that are critically ill.

14.
World J Clin Cases ; 9(1): 102-117, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33511176

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) affects more than one-quarter of the global population. Due to the lack of approved chemical agents, many patients seek treatment from traditional Chinese medicine (TCM) formulas. A variety of systematic reviews have been published regarding the effectiveness and safety of TCM formulas for NAFLD. AIM: To critically appraise available systematic reviews and sort out the high-quality evidence on TCM formulas for the management of NAFLD. METHODS: Seven databases were systematically searched from their inception to 28 February 2020. The search terms included "non-alcoholic fatty liver disease," "Chinese medicines," "systematic review," and their synonyms. Systematic reviews involving TCM formulas alone or in combination with conventional medications were included. The methodological quality and risk of bias of eligible systematic reviews were evaluated by using A Measure Tool to Assess Systematic Reviews 2 (AMSTAR 2) and Risk of Bias in Systematic Review (ROBIS). The quality of outcomes was assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: Seven systematic reviews were ultimately included. All systematic reviews were conducted based on randomized controlled trials and published in the last decade. According to the AMSTAR 2 tool, one systematic review was judged as having a moderate confidence level, whereas the other studies were rated as having a low or extremely low level of confidence. The ROBIS tool showed that the included systematic reviews all had a high risk of bias due to insufficient consideration of identified concerns. According to the GRADE system, only two outcomes were determined as high quality; namely, TCM formulas with the HuoXueHuaYu principle were better than conventional medications in ultrasound improvement, and TCM formulas were superior to antioxidants in alanine aminotransferase normalization. Other outcomes were downgraded to lower levels, mainly because of heterogeneity among studies, not meeting optimal information sample size, and inclusion of excessive numbers of small sample studies. Nevertheless, the evidence quality of extracted outcomes should be further downgraded when applying to clinical practice due to indirectness. CONCLUSION: The quality of available systematic reviews was not satisfactory. Researchers should avoid repeatedly conducting systematic reviews in this area and focus on designing rigorous randomized controlled trials to support TCM formula applications.

15.
J Ethnopharmacol ; 264: 113021, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32479885

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Liver fibrosis is an outcome of many chronic liver diseases and often results in cirrhosis, liver failure, and even hepatocarcinoma. Xiaoyaosan decoction (XYS) as a classical Traditional Chinese Medicine (TCM) formula is used to liver fibrosis in clinical practice while its mechanism is unclear. AIM OF THE STUDY: The aim of this study was to investigate the anti-fibrosis effect of XYS and to explore the molecular mechanisms by combining network pharmacology and transcriptomic technologies. MATERIALS AND METHODS: The carbon tetrachloride (CCl4)-induced liver fibrosis rat were treated with three doses of XYS. The liver fibrosis and function were evaluated by histopathological examination and serum biochemical detection. The fibrosis related protein a-SMA and collagen I were assessed by Western blot. Different expressed genes (DEGs) between XYS-treated group and model group were analyzed. The herb-component-target network was constructed combined the network pharmacology. The predict targets and pathways were validated by in vitro and in vivo experiments. RESULTS: With XYS treatment, the liver function was significantly improved, and fibrotic changes were alleviated. The a-SMA and collagen I expression levels in the liver were also decreased in XYS-treated rats compared with CCl4 model rats. 108 active components and 42 targets from 8 herbs constituted herb-compound-target network by transcriptomics and network pharmacology analysis. The KEGG pathway and GO enrichment analyses showed that the FoxO, TGFß, AMPK, MAPK, PPAR, and hepatitis B and C pathways were involved in the anti-fibrosis effects of XYS. In the liver tissues, p-FoxO3a and p-Akt expression levels were significantly increased in the CCl4 model group but decreased in the XYS-treated group. The TGFß1/Smad pathway and Akt/FoxO3 pathway were verified in LX2 cells by inhibiting phosphorylation of Smad3 and Akt activity, respectively. CONCLUSIONS: Our findings suggested that XYS markedly alleviated CCl4-induced liver fibrosis in histopathological and serum liver function analyses, and this effect may occur via the TGFß1/Smad and Akt/FoxO signaling pathways.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Proteína Forkhead Box O3/antagonistas & inibidores , Cirrose Hepática/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteína Smad3/antagonistas & inibidores , Fator de Crescimento Transformador beta/antagonistas & inibidores , Animais , Medicamentos de Ervas Chinesas/farmacologia , Proteína Forkhead Box O3/metabolismo , Cirrose Hepática/metabolismo , Masculino , Mapas de Interação de Proteínas/efeitos dos fármacos , Mapas de Interação de Proteínas/fisiologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta/metabolismo
16.
Front Immunol ; 11: 565759, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33329527

RESUMO

Signaling pathway between human leukocyte antigen (HLA)-G and immune inhibitory receptors immunoglobulin-like transcript (ILT)-2/4 has been acknowledged as one of immune checkpoints, and as a potential target for cancer immunotherapy. Like other immune checkpoints, inter- and even intratumor heterogeneity of HLA-G could render a rather complexity for HLA-G-target immunotherapy. However, little information for intratumor heterogeneity of HLA-G is available. In this study, HLA-G expression in a serial section of colorectal cancer (CRC) lesions from three CRC patients (each sample with serial section of 50 slides, 10 randomized slides for each antibody), three different locations within a same sample (five CRC), and three case-matched blocks that each includes 36 esophageal cancer samples, were evaluated with immunohistochemistry using anti-HLA-G antibodies (mAbs 4H84, MEM-G/1 and MEM-G/2 probing for all denatured HLA-G isoforms, 5A6G7, and 2A12 probing for denatured HLA-G5 and HLA-G6 isoforms). Our results revealed that, in addition to the frequently observed inter-tumor heterogeneity, intratumor heterogeneous expression of HLA-G is common in different areas within a tumor in CRC and esophageal cancer samples included in this study. Moreover, percentage of HLA-G expression probed with different anti-HLA-G antibodies also varies dramatically within a tumor. Given HLA-G has been considered as an important immune checkpoint, intratumor heterogeneity of HLA-G expression, and different specificity of anti-HLA-G antibodies being used among studies, interpretation and clinical significance of HLA-G expression in cancers should be with caution.


Assuntos
Neoplasias Colorretais/imunologia , Neoplasias Esofágicas/imunologia , Antígenos HLA-G/imunologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
17.
Exp Ther Med ; 20(4): 3578-3586, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32855711

RESUMO

The present study aimed to investigate the expression and significance of the mRNA of genes associated with autophagy and long non-coding RNA (lncRNA) GAS5 in peripheral blood mononuclear cells (PBMCs) of patients with ankylosing spondylitis (AS). The mRNA levels of microtubule-associated protein light chain 3 (LC3), Beclin1, autophagy-related gene (ATG)3, ATG5, ATG12, ATG 16 ligand 1 (ATG16L1) and lncRNA growth arrest-specific 5 (GAS5) in PBMCs from 60 patients with AS and 30 healthy controls (HC) were examined by reverse transcription-quantitative PCR. The correlations between the levels of LC3, Beclin1, ATG3, ATG5, ATG12 and ATG16L1 mRNA as well as lncRNA GAS5 levels with disease activity and laboratory parameters in patients with AS were determined by Spearman correlation analysis. In addition, the diagnostic value of lncRNA GAS5 for AS was explored through establishing a receiver operating characteristic (ROC) curve. The results indicated that, compared to the HCs, patients with AS had lower expression levels of LC3, ATG5, ATG12, ATG16L1 and lncRNA GAS5 in their PBMCs. Compared with those in patients with inactive AS, the levels of ATG5 and ATG12 were lower than those in patients with active AS. Of note, ATG5 and ATG12 mRNA levels were negatively correlated with disease activity indexes. lncRNA GAS5 was positively correlated with the expression of Beclin1, ATG3, ATG5, ATG12 and ATG16L1. The area under the ROC curve for the use of lncRNA GAS5 expression to diagnose AS was 0.808 with a 95% CI of 0.714-0.902. In conclusion, patients with AS had decreased expression of genes associated with autophagy and lncRNA GAS5. The extent of the reduction in ATG5 and ATG12 expression levels in patients with AS was correlated with the disease severity and activity. Furthermore, lncRNA GAS5 was a diagnostic indicator of AS.

18.
Fertil Steril ; 114(2): 301-310, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32624215

RESUMO

OBJECTIVE: To evaluate a novel micro-straw as an efficient, simple method for freezing a small number of human spermatozoa for intracytoplasmic sperm injection (ICSI). DESIGN: Prospective cohort study. SETTING: Sperm bank. PATIENT(S): Men with severe oligozoospermia or azoospermia undergoing a total of 143 ICSI cycles at the CITIC-Xiangya Hospital of Reproduction and Genetics from June 1, 2015, to June 31, 2019, and 20 donors at the Hunan Province Human Sperm Bank from 2001 to 2016. INTERVENTION(S): Analysis of sperm samples and clinical outcomes after sperm use. MAIN OUTCOME MEASURE(S): Clinical information, including number of motile sperm before and after freezing, freeze-thaw survival rates, two-pronuclear fertilization rates, clinical pregnancy, and early pregnancy loss rates after sperm use. RESULT(S): In the feasibility experiment using the micro-straw, we found a freeze-thaw survival rate of 73% ± 8.3% and no difference in normal sperm morphology, normal acrosome integrity, or DNA fragmentation index between the micro-straw and 1.8-mL cryotubes. The prospective cohort included 1,325 cases, and we collected sperm from testicular, epididymis, and ejaculation sources. We observed motile sperm in 1,294 (97.6%) of 1,325 frozen-thawed samples. Postthaw sperm were available for ICSI in 140 (97.9%) of 143 of cycles. The fertilization, cleavage, and high-quality embryo rates were 1,007 (81.7%) of 1,233; 995 (98.8%) of 1,007; and 537 (53.9%) of 995, respectively. Sixty-nine (49%) clinical pregnancies were achieved, and the miscarriage rate was 6 (8.6%) of 69. CONCLUSION(S): The micro-straw is suitable and clinically useful for the cryopreservation of small numbers of spermatozoa.


Assuntos
Azoospermia/terapia , Criopreservação/instrumentação , Oligospermia/terapia , Preservação do Sêmen/instrumentação , Injeções de Esperma Intracitoplásmicas , Espermatozoides/patologia , Aborto Espontâneo/etiologia , Azoospermia/patologia , Azoospermia/fisiopatologia , Fragmentação do DNA , Desenho de Equipamento , Estudos de Viabilidade , Feminino , Humanos , Masculino , Miniaturização , Oligospermia/patologia , Oligospermia/fisiopatologia , Gravidez , Taxa de Gravidez , Estudos Prospectivos , Fatores de Risco , Preservação do Sêmen/efeitos adversos , Índice de Gravidade de Doença , Contagem de Espermatozoides , Injeções de Esperma Intracitoplásmicas/efeitos adversos , Motilidade Espermática , Fatores de Tempo , Resultado do Tratamento
19.
Nat Commun ; 11(1): 3263, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32601286

RESUMO

Catalytic reductive coupling of two electrophiles and one unsaturated bond represents an economic and efficient way to construct complex skeletons, which is dominated by transition-metal catalysis via two electron transfer. Herein, we report a strategy of visible-light photoredox-catalyzed successive single electron transfer, realizing dearomative arylcarboxylation of indoles with CO2. This strategy avoids common side reactions in transition-metal catalysis, including ipso-carboxylation of aryl halides and ß-hydride elimination. This visible-light photoredox catalysis shows high chemoselectivity, low loading of photocatalyst, mild reaction conditions (room temperature, 1 atm) and good functional group tolerance, providing great potential for the synthesis of valuable but difficultly accessible indoline-3-carboxylic acids. Mechanistic studies indicate that the benzylic radicals and anions might be generated as the key intermediates, thus providing a direction for reductive couplings with other electrophiles, including D2O and aldehyde.

20.
Chemistry ; 26(66): 15052-15064, 2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-32614093

RESUMO

Over the past decades, organometallic complexes with precious elements, such as ruthenium and iridium, are widely used as visible-light photoredox catalysts. Recently, more and more complexes based on earth-abundant and inexpensive elements have been used as sensitizers in photochemistry. Although the photoexcited state lifetimes of iron complexes are typically shorter than those of traditional photosensitizers, the utilization of iron catalysts in photochemistry has sprung up owing to their abundance, low price, nontoxicity, and novel properties, including exhibiting ligand to metal charge transfer states. This concept focuses on recent advances in light-driven iron catalysis in organic transformations, including iron/photoredox dual catalysis, light-induced iron photoredox catalysis and light-induced generation of active iron catalysts. The prospect for the future of this field is also discussed.

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