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1.
Fitoterapia ; : 104547, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32173419

RESUMO

Five new indole alkaloids, kopsiofficines H-L (1-5), along with fourteen known alkaloids (6-19) were isolated from the stems of Kopsia officinalis. Their structures were elucidated by extensive NMR, mass spectroscopic analyses and comparison to the reported data. All the isolated compounds were evaluated their anti-inflammatory activities by inhibiting IL-1ß, PGE2 and TNF-α secretion in lipopolysaccharide (LPS)-activated RAW264.7 cells. Compounds 2, 3, 6, 7, 11, 12, 15, and 17 show significant anti-inflammatory activities. These results demonstrate pharmacodynamic substance basis of these folkloric claims.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32173525

RESUMO

Diabetic nephropathy (DN), the primary cause of end-stage renal disease (ESRD), is often accompanied by dyslipidemia, which is closely related to the occurrence and development of DN and even the progression to ESRD. Mitophagy, the selective degradation of damaged and dysfunctional mitochondria by autophagy, is a crucial mitochondrial quality control mechanism, and largely regulated by PINK1 (PTEN-induced putative kinase 1)/Parkin signaling pathway. In the present study, we demonstrated that PA induced mitochondrial damage and excessive mitoROS generation in podocytes. We also found PA treatment resulted in the activation of mitophagy by increasing co-localization of GFP-LC3 with mitochondria and enhancing the formation of mitophagosome, stabilization of PINK1 and mitochondrial translocation of Parkin, which indicated that PINK1/Parkin pathway was involved in PA-induced mitophagy in podocytes. Furthermore, inhibition of mitophagy by silencing Parkin dramatically aggravated PA-induced mitochondrial dysfunction, mitoROS production, and further enhanced PA-induced apoptosis of podocytes. Finally, we showed that PINK1/Parkin pathway were up-regulated in kidney of high fat diet (HFD)-induced obese rats. Taken together, our results suggest that PINK1/Parkin mediated mitophagy plays a protective role in PA-induced podocytes apoptosis through reducing mitochondrial ROS production and that enhancing mitophagy provides a potential therapeutic strategy for kidney diseases with hyperlipidemia, such as DN.

3.
Zhen Ci Yan Jiu ; 45(1): 74-6, 2020 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-32144913

RESUMO

OBJECTIVE: To dig the knowledge structure of lumbago's symptoms and acupoints in book Zhenjiu Jiayi Jing (A-B Classic of Acupuncture and Moxibustion) and Zhenjiu Dacheng (Compendium of Acupuncture and Moxibustion) in order to provide a possible scientific method for exploring their combination regularities in ancient Chinese medical books about acupuncture-moxibustion, and to investigate the feasibility and scientificity of the "association rule" in trimming the related ancient medical books and records. METHODS: The articles about lumbago's symptoms and employed acupoints were screened from classic me-dical book Zhenjiu Jiayi Jing and Zhenjiu Dacheng, followed by establishing a database. Then, the bidimensional correlation analysis about the lumbago-symptoms and symptoms-acupoints was conducted by using Apriori algorithm of Weka3.9.0 platform. RESULTS: A total of 153 entries about symptoms as spinalgia (31.68%) and cold limbs (25.74%) and the employed acupoints as Weizhong (BL40,17.60%), Shenshu (BL23, 9.60%) and Kunlun (BL60, 6.40%) are found. The top 3 supplemented acupoints are BL40 for concomitant symptoms of spinalgia, BL23 for cold limbs, and BL60 for dizzy symptoms. Regarding the paired acupoints for lumbago, the most frequently used ones are BL23-BL40 (30.40%).. CONCLUSION: In book Zhenjiu Jiayi Jing and Zhenjiu Dacheng, lumbago has chief symptoms of spinalgia and cold limbs that are mainly disorders of the Bladder Meridian of Foot Taiyang and Governor Vessel, and the acupoints of these two meridians are frequently selected in combination with some specific acupoints.


Assuntos
Dor Lombar , Meridianos , Moxibustão , Pontos de Acupuntura , Livros , Humanos
4.
Einstein (Sao Paulo) ; 18: e0AO5052, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-32159606

RESUMO

OBJECTIVE: To compare screw fixation strength for subtalar arthrodesis. METHODS: Eight matched pairs of cadaver feet underwent subtalar joint arthrodesis with two 7.3mm cannulated screws. Randomization was used to assign screw orientation, such that one foot in each pair was assigned dorsal to plantar screw orientation (DP Group), and the other foot, plantar to dorsal orientation (PD Group). Standard surgical technique with fluoroscopy was used for each approach. Following fixation, each specimen was loaded to failure with a Bionix ® 858 MTS device, applying a downward axial force at a distance to create torque. Torque to failure was compared between DP and PD Groups using Student's t test, with p=0.05 used to determine statistical significance. RESULTS: Statistical analysis demonstrated that the mean torque to failure slightly favored the DP Group (37.3Nm) to the PD Group (32.2Nm). However, the difference between the two groups was not statistically significant (p=0.55). CONCLUSION: In subtalar arthrodesis, there is no significant difference in construct strength between dorsal-to-plantar and plantar-to-dorsal screw orientation. The approach chosen by the surgeon should be based on factors other than the biomechanical strength of the screw orientation.

5.
J Natl Med Assoc ; 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32197898

RESUMO

PURPOSE: Black breast cancer patients delay and underutilize adjuvant breast cancer therapies; yet, very few studies have specifically examined Black women's attitudes toward breast cancer therapy. This study observed the influence of self-reported interpersonal processes of care (e.g. self-efficacy) clinical and sociodemographic factors and sociocultural (e.g. religiosity), related to Black breast cancer patients' attitudes toward radiation and systemic therapies (chemotherapy and adjuvant endocrine therapy - "AET"). METHODS: This was a secondary analysis of data from the Narrowing Gaps in Adjuvant Therapy Study (2006-2011). The analysis included 210 Black women who were newly diagnosed with breast cancer. Bivariate and multiple regression analyses were performed between independent variables (e.g., demographics) and three outcome variables (chemotherapy, AET, and radiation therapy) to asses women's perceptions of therapy type. The lasso method was used to select variables correlated with therapy attitudes. RESULTS: Most women reported negative attitudes toward AET (56%) and radiation (54%); fewer negative attitudes were observed toward chemotherapy (47%). Higher education and greater perceived susceptibility of a recurrence were associated with more positive attitudes toward chemotherapy. Regarding radiation therapy, women with greater patient satisfaction were more likely to have more positive attitudes. CONCLUSIONS: Our study findings may aid in the development of behavioral interventions targeted to mitigate Black women breast cancer treatment disparities. We found modifiable factors (e.g. communication, satisfaction ratings) that support opportunities for clinicians to better address Black women's needs regarding adjuvant treatment options. The development of tailored interventions for newly diagnosed Black breast cancer patients on patient related factors in health care are warranted for Black women with lower educational levels.

6.
Neurochem Int ; : 104731, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32201280

RESUMO

Increasing evidences support that glial connexins are involved in the demyelination pathology of multiple sclerosis (MS), a chronic inflammatory demyelinating disorder. Here, we review the data from patients with MS and animal models of MS that implicate connexins in demyelination. Connexins expressed in oligodendrocytes and astrocytes show diverse changes at the different phases of MS. Loss of oligodendrocyte or astrocyte connexins contributes to demyelination and exaggerates the pathology of MS. Channel-dependent and -independent connexins are involved in the pathology of demyelination, which is related with myelin integrity, metabolic homeostasis, the brain-blood barrier, the immune cell infiltration, and the inflammatory response. A comprehensive understanding of connexin function in demyelination may provide new therapeutic targets for MS.

7.
J Food Sci ; 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32180223

RESUMO

Variations in the taste quality of no-added-nitrite Chinese bacon (unsmoked) during processing were investigated using 1 H-NMR and multivariate data analysis. The results showed that 21 metabolites were dominant during processing, which involved marinating, air-drying, fermentation, and baking, including amino acids, sugars, organic acids, nucleic acids and their derivatives, and alkaloids. The contents of isoleucine, leucine, valine, alanine, acetate, glutamate, succinate, glycine, sucrose, tyrosine, and phenylalanine increased continuously throughout the process. The lactate, creatine, carnosine, betaine, taurine, hypoxanthine, and AMP contents all significantly increased after baking; the inosine content significantly increased after fermentation and then decreased; the histamine content significantly increased after air-drying and then decreased; and the histidine content decreased. Each processing treatment promoted taste formation in no-added-nitrite Chinese bacon (unsmoked), especially baking. The baking point owned relatively higher levels of metabolites and sensory evaluation compared to other treatments. Sensory evaluation revealed that the ultimate taste of Chinese bacon (unsmoked) at the end of baking tended toward umami (glutamate), sweetness (AMP), and sourness (lactate). The first and second principal components explained 74.0% and 13.4% of the variables, respectively. These findings indicated the potential of NMR-based metabolomics for assessing the taste quality of no-added-nitrite Chinese bacon (unsmoked), which could contribute to a better understanding of taste compound changes in meat products. PRACTICAL APPLICATION: Nitrite is commonly used in Chinese bacon (unsmoked), but excessive intake is not good for human health. Nitrite has been replaced with nitrite substitutes to prepare no-added-nitrite Chinese bacon (unsmoked). The metabolites of no-added-nitrite Chinese bacon (unsmoked) were detected to determine the key treatment that contributes to the formation of taste during processing. This study determined the main taste components of no-added-nitrite Chinese bacon (unsmoked) and its formation process, which provides new insight into the production and characteristics of flavor in Chinese bacon (unsmoked).

8.
Hand (N Y) ; : 1558944719901319, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32036706

RESUMO

Background: Although the diagnosis of thoracic outlet syndrome (TOS) is often missed, outcomes from surgical intervention significantly improve patient satisfaction. This article seeks to highlight patient characteristics, intraoperative findings, and both short and long-term outcomes of thoracic outlet decompression in the adolescent population. Methods: A retrospective chart review of patients between the ages of 13 and 21 years with a clinical diagnosis of neurogenic thoracic outlet syndrome (NTOS) who were treated surgically between 2000 and 2015 was performed. Data points including preoperative patient characteristics and intraoperative findings were collected. In addition, patient-reported outcome scores, including Visual Analog Scale (VAS), Single Assessment Numeric Evaluation (SANE), Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) questionnaire, Cervical Brachial Symptom Questionnaire (CBSQ), and NTOS index, were obtained for a cohort of patients with follow-up ranging from 2 to 15 years. Results: The study population consisted of 54 patients involving 61 extremities. The most common procedures included neurolysis of the supraclavicular brachial plexus (60, 98.4%), anterior scalenectomy (59, 96.7%), and middle scalenectomy (54, 88.5%). First rib resection (FRR) was performed in 28 patients (45.9%). Long-term outcomes were collected for 24 (44%) of 54 patients with an average follow-up of 69.5 months (range, 24-180 months). The average VAS improved from 7.5 preoperatively to 1.8 postoperatively. The average SANE increased from 28.9 preoperatively to 85.4 postoperatively. The average postoperative scores were 11.4 for the QuickDASH, 27.4 for the CBSQ, and 17.2 for the NTOS index. Subgroup analysis of patients having FRR (28, 45.9%) demonstrated no difference in clinical outcome measures compared with patients who did not have FRR. Conclusion: Surgical treatment of NTOS in adolescent patients has favorable intermediate and long-term outcomes.

9.
Nanoscale ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32022050

RESUMO

Self-driven and continuous directional transport of water droplets in an oil environment has great potential applications in microfluidics, oil-water separation, etc. Nevertheless, most current studies exploit water behaviors occurring in air, and the directional regulation of water in a viscous oil medium remains a challenge. In this work, a superhydrophilic geometry-gradient stainless steel platform with nanoparticle-covered nanoripple structures is proposed using femtosecond laser direct writing technology. The as-prepared platform spontaneously and directionally transported water droplets in the oil environment from the minor side to the large side of the trapezoidal platform surface, but not in the opposite direction. The transport velocity of water droplets as a function of trapezoid angle and tilt angle of the as-prepared platform was investigated in detail. In addition, a pumpless under-oil water transport platform was successfully prepared on other substrates including Ti and Ni sheets, polyimide film, and C cloth, and exhibited transport capabilities when the platform was flexed and combined into various shapes. This work offers insight into the simple fabrication of a flexible and substrate-independent pumpless under-oil directional transport device for water.

10.
Arthroscopy ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32057988

RESUMO

PURPOSE: To evaluate the feasibility of arthroscopic reduction percutaneous fixation (ARPF) in the treatment of isolated medial malleolar fracture and to compare the results with those of conventional open reduction internal fixation (ORIF). METHODS: This prospective study enrolled 77 patients with isolated medial malleolar fracture between November 2011 and February 2016. The patients were assigned to the ARPF (n = 34) and ORIF (n = 43) groups. The Olerud-Molander Ankle Score (OMAS), ankle range of motion (ROM), visual analog scale, and radiographic evaluation were determined at the scheduled follow-up. RESULTS: In the ARPF group, 11 of 34 (32.4%) patients had chondral lesions. Tears of the deltoid ligament and anterior inferior tibiofibular ligament were noted in 3 (8.8%) and 15 (44.1%) patients, respectively. The mean follow-up was 5 years. The mean OMAS was higher in the ARPF group than in the ORIF group. The differences were statistically significant at 6 months (80.2 ± 4.0 for ARPF vs. 77.2 ± 4.1 for ORIF, P = 0.005) and 1 year (92.9 ± 4.9 vs. 88.1 ± 4.6, P < 0.001), but not at the latest follow-up (P = 0.081). Ankle ROM was markedly improved in the ARPF group unlike in the ORIF group at 6 months (dorsiflexion: P = 0.025; plantar flexion: P < 0.001) and 1 year (dorsiflexion and plantar flexion: P < 0.001). The improvement remained present at the latest follow-up in plantar flexion (P = 0.001) but not in dorsiflexion (P = 0.354). CONCLUSIONS: Arthroscopy-assisted reduction is a feasible alternative modality with superior short-term outcomes for treating isolated medial malleolar fracture, but its superiority may be attenuated in the intermediate term.

11.
PeerJ ; 8: e8543, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32110485

RESUMO

Classical swine fever (CSF) is a disease that is characterized by diffuse hemorrhaging, high fever, and high mortality rates. The pro-inflammatory characteristics of allograft inflammatory factor 1 (AIF1) have been well documented; however, insufficient attention has been given to porcine AIF1. In the present study, AIF1 was identified as a key player contributing to CSFV Shimen infection in porcine alveolar macrophage (PAM) 3D4/21 cell line. Our evaluation showed that AIF1 mRNA and protein are expressed at a time-dependent high level in CSFV Shimen-infected PAM 3D4/21 cells. The transcription and translation of IL6 were also significantly upregulated in infected PAM 3D4/21 cells. By utilizing overexpression RNAs approach, we showed that the cellular AIF1 induced an increased IL6 in PAM 3D4/21 cells. Furthermore, silencing of AIF1 suppressed CSFV Shimen-induced IL6 production in PAM 3D4/21 cells and also inhibited CSFV replication, whereas overexpression of recombinant AIF1 was beneficial for the replication of CSFV Shimen and promoting IL6 production in CSFV Shimen-infected PAM 3D4/21 cells. It is suggested CSFV Shimen induced IL6 in PAM 3D4/21 cells via AIF1 activation, which help clarify the AIF1-related inflammatory processes that occur on CSFV Shimen infected macrophages.

12.
Mol Microbiol ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32039533

RESUMO

The Lyme disease bacterium Borrelia burgdorferi has 7-11 periplasmic flagella (PF) that arise from the cell poles and extend toward the midcell as a flat-ribbon, which is distinct from other bacteria. FlhF, a signal recognition particle (SRP)-like GTPase, has been found to regulate the flagellar number and polarity; however, its role in B. burgdorferi remains unknown. B. burgdorferi has an FlhF homolog (BB0270). Structural and biochemical analyses show that BB0270 has a similar structure and enzymatic activity as its counterparts from other bacteria. Genetics and cryo-electron tomography studies reveal that deletion of BB0270 leads to mutant cells that have less PF (4 ± 2 PF per cell tip) and fail to form a flat-ribbon, indicative of a role of BB0270 in the control of PF number and configuration. Mechanistically, we demonstrate that BB0270 localizes at the cell poles and controls the number and position of PF via regulating the flagellar protein stability and the polar localization of the MS-ring protein FliF. Our study not only provides the detailed characterizations of BB0270 and its profound impacts on flagellar assembly, morphology and motility in B. burgdorferi, but also unveils mechanistic insights into how spirochetes control their unique flagellar patterns.

13.
Instr Course Lect ; 69: 509-522, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32017749

RESUMO

Numerous nerve disorders affect the foot and ankle, and specificity is essential for diagnosis. We review a systematic process to conduct a history and physical examination for nerve disorders and how to categorize these pathologies. Several common nerve-related pathologies of the foot and ankle are then described. Finally, we discuss systemic neurologic conditions which can cause symptoms in the foot and ankle. A vast array of treatment options exist for painful nerve lesions of the foot: both nonsurgical and surgical. Treatment options depend on the affected nerve's function and location within the foot. Essential nerves will be managed much differently than nonessential nerves. Also important to consider is whether this is the initial treatment, treatment following one recurrence, or treatment following multiple recurrences. After the proper diagnosis is made, consideration of these principles should allow for early and effective interventions to be made. Recalcitrant nerve conditions of the foot and ankle can represent a management challenge. As with primary nerve disorders, surgical management is warranted in cases where conservative management fails. Furthermore, patients may continue to experience neurologic complications or recurrence of symptoms even after surgical intervention, at which point further surgical procedures may be undertaken. Neurolysis, transection with or without containment, barrier procedures, and peripheral nerve stimulation are viable potential surgical options for patients with chronic or recurrent nerve pain, depending upon patient-specific underlying pathology.


Assuntos
Tornozelo , , Neuralgia/terapia , Articulação do Tornozelo , Humanos , Exame Físico
14.
Chem Commun (Camb) ; 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32108193

RESUMO

The black, small-bandgap semiconducting framework Eu-dfdmat features extensive Eu3+-sulfur bridges from the linear linker 2,5-difluoro-3,6-dimercaptoterephthalate (dfdmt). Each Eu center is chelated to four dfdmt linkers to form an anionic coordination sphere involving four carboxyl O and four mercapto S centers (EuO4S4), wherein the charge buildup can be alleviated by the electron-withdrawing fluoro groups. The extensive metal-linker bonding, together with a trace of Eu2+ species, appears to boost electronic interaction in the 2D net, generating a small band gap of 1.31 eV (946 nm), albeit a modest conductivity (e.g., 10-6 S m-1). The crystals also exhibit persistent EPR signals indicative of organic radicals (g = 2.002). The Eu-dfdmt solid are stable in air and can be exfoliated into ultrathin nanosheets (ca. 5 nm; 6-8 layers).

15.
Food Funct ; 11(2): 1845-1855, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32067021

RESUMO

Short chain fatty acids (SCFAs) are produced when indigestible carbohydrates, such as fiber and resistant starch, undergo fermentation by specific microbiota in the hindgut. This study was designed to investigate the effects of different SCFAs on the glucolipid metabolism and appetite regulation of pigs. In a 28-day experiment, 30 barrows were divided into five groups: (1) control, (2) 0.1% sodium acetate, (3) 0.1% sodium propionate, (4) 0.1% sodium butyrate, and (5) 0.1% mixed sodium SCFAs (in the ratio of 3 : 1 : 1, respectively). Acetate administration reduced the average daily feed intake and average daily body weight gain of pigs (P < 0.05), decreased serum triglyceride (TG), total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-c) concentrations (P < 0.05), increased serum glucagon-like peptide 1 (GLP-1), peptide YY (PYY) and leptin concentrations (P < 0.05), down-regulated fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC) and sterol regulatory element binding protein 1c (SREBP-1c) mRNA expressions in the liver (P < 0.05), enhanced silent information regulator1 (SIRT1) mRNA expression in the longissimus dorsi (P < 0.05), and up-regulated free fatty acids receptor 2 (FFAR2) and PYY mRNA expressions in the colon (P < 0.05). Propionate administration also decreased serum TG, TC, and LDL-c concentrations (P < 0.05), increased serum GLP-1, PYY and leptin concentrations (P < 0.05), down-regulated glucose-6-phosphatase (G6PC) mRNA expression in the liver (P < 0.05), enhanced PPARγ coactivator-1α (PGC-1α) mRNA expression in the liver (P < 0.05), stimulated SIRT1 mRNA expression in the longissimus dorsi (P < 0.05), and up-regulated G6PC and glucagon mRNA expressions in the colon (P < 0.05). Butyrate administration down-regulated G6PC mRNA expression in the liver (P < 0.05), enhanced PGC-1α mRNA expression in the liver (P < 0.05), and increased lipase hormone-sensitive (LIPE) and carnitine palmitoyltransferase-1α (CPT-1α) mRNA expressions in the longissimus dorsi (P < 0.05). Overall, these results suggested that SCFAs could reduce lipogenesis, and enhance lipolysis in different tissues of pigs via regulating related hormones and genes, which would further illustrate the mechanisms underlying the beneficial effects of SCFAs on appetite and body weight control.

16.
Parasit Vectors ; 13(1): 84, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32070423

RESUMO

BACKGROUND: Infection with the apicomplexan protozoan parasite T. gondii can cause severe and potentially fatal cerebral and ocular disease, especially in immunocompromised individuals. The anticoccidial ionophore drug monensin has been shown to have anti-Toxoplasma gondii properties. However, the comprehensive molecular mechanisms that underlie the effect of monensin on T. gondii are still largely unknown. We hypothesized that analysis of T. gondii transcriptional changes induced by monensin treatment can reveal new aspects of the mechanism of action of monensin against T. gondii. METHODS: Porcine kidney (PK)-15 cells were infected with tachyzoites of T. gondii RH strain. Three hours post-infection, PK-15 cells were treated with 0.1 µM monensin, while control cells were treated with medium only. PK-15 cells containing intracellular tachyzoites were harvested at 6 and 24 h post-treatment, and the transcriptomic profiles of T. gondii-infected PK-15 cells were examined using high-throughput RNA sequencing (RNA-seq). Quantitative real-time PCR was used to verify the expression of 15 differentially expressed genes (DEGs) identified by RNA-seq analysis. RESULTS: A total of 4868 downregulated genes and three upregulated genes were identified in monensin-treated T. gondii, indicating that most of T. gondii genes were suppressed by monensin. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of T. gondii DEGs showed that T. gondii metabolic and cellular pathways were significantly downregulated. Spliceosome, ribosome, and protein processing in endoplasmic reticulum were the top three most significantly enriched pathways out of the 30 highly enriched pathways detected in T. gondii. This result suggests that monensin, via down-regulation of protein biosynthesis in T. gondii, can limit the parasite growth and proliferation. CONCLUSIONS: Our findings provide a comprehensive insight into T. gondii genes and pathways with altered expression following monensin treatment. These data can be further explored to achieve better understanding of the specific mechanism of action of monensin against T. gondii.

17.
J Nutr Biochem ; 77: 108297, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32006744

RESUMO

This study investigated the effects of resveratrol and miR-22-3p on muscle fiber type conversion in mouse C2C12 myotubes. Here we showed that resveratrol significantly increased the protein level of slow myosin heavy chain (MyHC) and the activities of succinic dehydrogenase and malate dehydrogenase, as well as markedly decreased the protein level of fast MyHC and the activity of lactate dehydrogenase. Immunofluorescence staining showed that resveratrol remarkably upregulated the number of slow MyHC-positive myotubes and downregulated the number of fast MyHC-positive myotubes, suggesting that resveratrol promoted muscle fiber type conversion from fast-twitch to slow-twitch in C2C12 myotubes. We also showed that miR-22-3p had an opposite function on muscle fiber type conversion and resveratrol was able to repress the expression of miR-22-3p. Furthermore, AMP-activated protein kinase (AMPK) inhibitor Compound C and miR-22-3p mimics could attenuate and eliminate muscle fiber type conversion from fast-twitch to slow-twitch cause by resveratrol, respectively. Together, we provided the first evidence that resveratrol promotes muscle fiber type conversion from fast-twitch to slow-twitch via miR-22-3p and AMPK/SIRT1/PGC-1α pathway in C2C12 myotubes.

18.
J Mol Med (Berl) ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32072231

RESUMO

Embryo implantation is an essential and complex process in mammalian reproduction. However, little evidence has indicated the involvement of autophagy during embryo implantation. To determine the possible role of autophagy in uterine of pregnant mice during the peri-implantation stage, we first examined the expression of autophagy-related markers ATG5 and LC3 on day 4, 5, and 6 of pregnancy (D4, D5, and D6, respectively). Compared with expression on D4, downregulation of the autophagy-related markers was observed on D5 and D6, the days after the embryo attached to the receptivity endometrium. Further examination showed that autophagy-related markers ATG5, ATG12, LC3, cathepsin B, and P62 at the implantation site were significantly decreased when comparing with the inter-implantation site. Fewer number of autophagosomes at the implantation site were also observed by transmission electron microscopy. To confirm the functional role of autophagy during embryo implantation in mice, we administered the autophagy inhibitor 3-methyladenine and chloroquine to mice. After treated with 3-methyladenine, the expression of decidual markers HOXA10 and progesterone receptor were significantly reduced. Furthermore, a reduction in implantation sites and increase in the HOXA10 and PR protein levels were observed in response to chloroquine treatment. In addition, impaired uterine decidualization and dysregulation of the PR and HOXA10 protein levels was observed after autophagy inhibited by 3-methyladenine and chloroquine in in vivo artificial decidualization mouse model. In the last, LC3 and P62 were also observed in normal human proliferative, secretory, and decidua tissues. In conclusion, endometrial autophagy may be essential for embryo implantation, and it may be associated with endometrial decidualization during early pregnancy. KEY MESSAGE: • Autophagy-related markers were significantly decreased at implantation site. • Autophagy inhibition results in abnormal decidualization. • Autophagy is essential for embryo implantation.

19.
Regul Toxicol Pharmacol ; 113: 104623, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32088183

RESUMO

In the current study, to support the safety assessment of ethanamizuril as a new potent anticoccidial agent of triazine compounds, a reproductive toxicity and teratogenic potential assay of ethanamizuril was investigated. Groups of 30 males and 30 females were administered 0, 0.02, 0.1 or 0.2 mg/ml ethanamizuril by gastric incubation through a 10-week prebreed period as well as during mating, gestation, parturition and lactation in any generation. Compared to the control group, no test compound-related changes in copulation index, fertility index, gestation length, litter size, pup weight, pup sex ratio, pup viability, epididymal sperm counts or motility or other functional reproductive measures were noted in any generation, except few significant changes in high dose group in the number of sperm motility at III level in F0 males and the body weights of GD14 and GD21 in F1 rats. There were no compound-related necropsy findings or effects on organ weight. Histopathologic examinations revealed no evidence of compound-related changes in any organs including the reproductive organs of both sexes. In conclusion, long-term administrated 0.2, 1.0 and 2.0 mg/kg of ethanamizuril by means of oral gavage did not affect the reproduction of Sprague-Dawley rats and the development ability of their offspring under the experimental conditions.

20.
Int J Biochem Cell Biol ; 122: 105731, 2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32097728

RESUMO

Pancreatic cancer is a leading cause of cancer-related death worldwide. Cisplatin is an essential drug treating patients with BRCA1/2 or PALB2 mutations. Whether other genetic determinants of cisplatin sensitivity exist and their underlying mechanisms remain unclear. Immunohistochemistry was used to determine METTL14 expression in pancreatic cancer tissues and non-tumoural tissues. Cell proliferation was detected with CCK-8 assays. Apoptosis was analysed via Western blotting and flow cytometry, and autophagy was analysed via Western blotting and immunofluorescence. In this work, we found higher METTL14 expression in pancreatic cancer tissues than in non-tumoural tissues, and METTL14 expression was associated with pathological characteristics. Downregulation of METTL14 with siRNA sensitized pancreatic cancer cells to cisplatin. Specifically, apoptosis and autophagy were significantly enhanced in METT14 knockdown cells compared with control cells after treatment with cisplatin. Mechanistically, the AMPKα, ERK1/2 and mTOR signalling pathways were disturbed by downregulation of METTL14. We further found that METTL14 knockdown-mediated autophagy was dependent on mTOR signalling and that mTOR activation decreased autophagy to the level observed in the control group. Collectively, our results indicate that METTL14 is upregulated in pancreatic cancer, downregulation of METTL14 sensitizes pancreatic cancer cells to cisplatin by enhancing apoptosis, and autophagy is improved via an mTOR signalling-dependent pathway.

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