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1.
Curr Med Sci ; 44(2): 450-461, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38639827

ABSTRACT

OBJECTIVE: Cymbopogon citratus (DC.) Stapf is a medicinal and edible herb that is widely used for the treatment of gastric, nervous and hypertensive disorders. In this study, we investigated the cardioprotective effects and mechanisms of the essential oil, the main active ingredient of Cymbopogon citratus, on isoproterenol (ISO)-induced cardiomyocyte hypertrophy. METHODS: The compositions of Cymbopogon citratus essential oil (CCEO) were determined by gas chromatography-mass spectrometry. Cardiomyocytes were pretreated with 16.9 µg/L CCEO for 1 h followed by 10 µmol/L ISO for 24 h. Cardiac hypertrophy-related indicators and NLRP3 inflammasome expression were evaluated. Subsequently, transcriptome sequencing (RNA-seq) and target verification were used to further explore the underlying mechanism. RESULTS: Our results showed that the CCEO mainly included citronellal (45.66%), geraniol (23.32%), and citronellol (10.37%). CCEO inhibited ISO-induced increases in cell surface area and protein content, as well as the upregulation of fetal gene expression. Moreover, CCEO inhibited ISO-induced NLRP3 inflammasome expression, as evidenced by decreased lactate dehydrogenase content and downregulated mRNA levels of NLRP3, ASC, CASP1, GSDMD, and IL-1ß, as well as reduced protein levels of NLRP3, ASC, pro-caspase-1, caspase-1 (p20), GSDMD-FL, GSDMD-N, and pro-IL-1ß. The RNA-seq results showed that CCEO inhibited the increase in the mRNA levels of 26 oxidative phosphorylation complex subunits in ISO-treated cardiomyocytes. Our further experiments confirmed that CCEO suppressed ISO-induced upregulation of mt-Nd1, Sdhd, mt-Cytb, Uqcrq, and mt-Atp6 but had no obvious effects on mt-Col expression. CONCLUSION: CCEO inhibits ISO-induced cardiomyocyte hypertrophy through the suppression of NLRP3 inflammasome expression and the regulation of several oxidative phosphorylation complex subunits.


Subject(s)
Cymbopogon , Oils, Volatile , Oils, Volatile/pharmacology , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein , Cymbopogon/chemistry , Cymbopogon/metabolism , Isoproterenol , Myocytes, Cardiac/metabolism , Oxidative Phosphorylation , RNA, Messenger/metabolism , Hypertrophy/chemically induced , Hypertrophy/drug therapy , Hypertrophy/metabolism
2.
J Inorg Biochem ; 251: 112433, 2024 02.
Article in English | MEDLINE | ID: mdl-38043136

ABSTRACT

The p53 protein plays a major role in cancer prevention, and over 50% of cancer diagnoses can be attributed to p53 malfunction. p53 incorporates a structural Zn site that is required for proper protein folding and function, and in many cases point mutations can result in loss of the Zn2+ ion, destabilization of the tertiary structure, and eventual amyloid aggregation. Herein, we report a series of compounds designed to act as small molecule stabilizers of mutant p53, and feature Zn-binding fragments to chaperone Zn2+ to the metal depleted site and restore wild-type (WT) function. Many Zn metallochaperones (ZMCs) have been shown to generate intracellular reactive oxygen species (ROS), likely by chelating redox-active metals such as Fe2+/3+ and Cu+/2+ and undergoing associated Fenton chemistry. High levels of ROS can result in off-target effects and general toxicity, and thus, careful tuning of ligand Zn2+ affinity, in comparison to the affinity for other endogenous metals, is important for selective mutant p53 targeting. In this work we show that by using carboxylate donors in place of pyridine we can change the relative Zn2+/Cu2+ binding ability in a series of ligands, and we investigate the impact of donor group changes on metallochaperone activity and overall cytotoxicity in two mutant p53 cancer cell lines (NUGC3 and SKGT2).


Subject(s)
Metallochaperones , Tumor Suppressor Protein p53 , Zinc , Humans , Cell Line, Tumor , Chelating Agents , Metallochaperones/chemistry , Reactive Oxygen Species/metabolism , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Zinc/metabolism , Protein Binding
3.
China Pharmacy ; (12): 744-749, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1013113

ABSTRACT

OBJECTIVE To evaluate the effects of ivabradine on vascular endothelial function in patients with coronary artery disease. METHODS PubMed, Embase, the Cochrane Library, Web of Science, CNKI, Wanfang Data, VIP and CBM databases were retrieved to collect randomized controlled trials (RCTs) about ivabradine (intervention group) versus placebo or β-blocker (control group) from the inception to Mar. 20th 2023. The meta-analysis was performed by using RevMan 5.4 software after literature screening, data extraction and quality evaluation. RESULTS A total of 12 RCTs were included, involving 1 206 patients. The results of meta-analysis showed that the levels of flow-mediated dilation (FMD) [MD=1.71, 95%CI (0.96, 2.46), P<0.000 01] and nitric oxide (NO) [MD=5.80, 95%CI (5.02, 6.59), P<0.000 01] in the intervention group were significantly higher than control group, while endothelin-1(ET-1) level was significantly lower than control group [MD=-7.45, 95%CI (-8.42, -6.47), P<0.000 01]. There was no statistical significance in nitroglycerin-mediated dilation (NMD) level between 2 groups [MD=0.13, 95%CI(-0.74, 1.00), P=0.77]. Subgroup analyses based on the different medications and intervention time in the control group showed better improvement in FMD level of patients receiving ivabradine, compared with placebo (P<0.05); compared with placebo and β-blocker, the level of NO in patients receiving ivabradine was improved significantly (P<0.05), while ET-1 level was decreased significantly (P<0.05). Regardless of the duration of the intervention, the levels of FMD, NO, and ET-1 in the intervention group were significantly improved compared to the control group (P<0.01), while the difference in NMD was not statistically significant (P>0.05). CONCLUSIONS Ivabradine can improve vascular endothelial function in patients with coronary artery disease.

4.
Environ Sci Pollut Res Int ; 30(41): 93731-93743, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37515622

ABSTRACT

The gastrointestinal microbiota, a complex ecosystem, is involved in the physiological activities of hosts and the development of diseases. Birds occupy a critical ecological niche in the ecosystem, performing a variety of ecological functions and possessing a complex gut microbiota composition. However, the gut microbiota of wild and captive birds has received less attention in the same region. We profiled the fecal gut microbiome of wild wintering whooper swans (Cygnus Cygnus; Cyg group, n = 25), captive black swans (Cygnus Atratus; Atr group, n = 20), and mute swans (Cygnus Olor; Olor group, n = 30) using 16S rRNA gene sequencing to reveal differences in the gut microbial ecology. The results revealed that the three species of swans differed significantly in terms of the alpha and beta diversity of their gut microbiota, as measured by ACE, Chao1, Simpson and Shannon indices, principal coordinates analysis (PCoA) and non-metricmulti-dimensional scaling (NMDS) respectively. Based on the results of the linear discriminant analysis effect size (LEfSe) and random forest analysis, we found that there were substantial differences in the relative abundance of Gottschalkia, Trichococcus, Enterococcus, and Kurthia among the three groups. Furthermore, an advantageous pattern of interactions between microorganisms was shown by the association network analysis. Among these, Gottschalkia had the higher area under curve (AUC), which was 0.939 (CI = 0.879-0.999), indicating that it might be used as a biomarker to distinguish between wild and captive black swans. Additionally, PICRUSt2 predictions indicated significant differences in gut microbiota functions between wild and captive trumpeter swans, with the gut microbiota functions of Cyg group focusing on carbohydrate metabolism, membrane transport, cofactor, and vitamin metabolism pathways, the Atr group on lipid metabolism, and the Olor group on cell motility, amino acid metabolism, and replication and repair pathways. These findings showed that the gut microbiota of wild and captive swans differed, which is beneficial to understand the gut microecology of swans and to improve regional wildlife conservation strategies.


Subject(s)
Anseriformes , Gastrointestinal Microbiome , Animals , Wetlands , Ecosystem , RNA, Ribosomal, 16S , Birds , Ducks , China
5.
J Asian Nat Prod Res ; 25(11): 1085-1096, 2023 Nov.
Article in English | MEDLINE | ID: mdl-36951955

ABSTRACT

The efficient total synthesis of anti-tumor natural product pongaflavone (1) was described starting from commercially available 2,4-dihydroxyacetophenone (9) via seven steps and in 16% overall yield. Its two natural analogues pongachromene (2) and 7,8-(2",2"-dimethylpyrano)-5,3',4'-trihydroxy-3-methoxyflavone (3) were also synthesized following the similar procedure with the yields of 11% and 18%, respectively. Their preliminary anti-tumor activities were evaluated by the inhibition effect on A549 cells. The result showed that this kind of natural products exhibited different levels of anti-tumor activity. Among them, pongachromene (2) displayed the best anti-tumor activity.


Subject(s)
Biological Products , Flavonoids , Flavonoids/chemical synthesis
6.
Nutrients ; 15(4)2023 Feb 14.
Article in English | MEDLINE | ID: mdl-36839314

ABSTRACT

Obesity is regarded as an abnormal or excessive buildup of fat that may be bad for health and is influenced by a combination of intestinal flora, genetic background, physical activity level and environment. Symbiotic supplementation may be a realistic and easy therapy for the reversal of obesity and associated metabolic problems. In this study, we chose two Bifidobacterium species, three Lactobacilli species and four prebiotics to make a new symbiotic formulation. High or low doses of the symbiotic were administered to rats, and biochemical indicators were recorded to assess the biological effects in a high-fat-diet-induced rat model. The underlying mechanisms were explored by integrating 16S rRNA sequencing with an extensively targeted metabolome. High-dose symbiotic supplementation was effective in reducing obesity and concomitant metabolic syndrome. The high-dose symbiotic also significantly increased the abundance of Blautia, which was negatively correlated with taurocholic acid and the main differential metabolites involved in amino acid and bile acid metabolism. While the low-dose symbiotic had some therapeutic effects, they were not as strong as those at the high dose, demonstrating that the effects were dose-dependent. Overall, our novel symbiotic combination improved plasma glucose and lipid levels, shrunk adipocyte size, restored liver function, increased the abundance of Blautia and adjusted bile acid and amino acid metabolism.


Subject(s)
Metabolic Syndrome , Rats , Animals , RNA, Ribosomal, 16S , Obesity/metabolism , Diet, High-Fat , Bile Acids and Salts
7.
Fitoterapia ; 165: 105398, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36563762

ABSTRACT

Piper longum has a specific aroma and spicy taste. In addition to edible value, current studies have shown that piper longum also has pharmacological activities such as anti-platelet aggregation, anti-inflammation, anti-cancer, anti-diabetes and anti-depression. Piperlongumine is an alkaloid isolated from Piper longum. Based on our previous studies, four Piperlongumine analogs were synthesized, and their anti-platelet aggregation activities were evaluated. Among them, compound 8 has the strongest anti-platelet aggregation activity. Therefore, compound 8 was docked with stroke-related protein targets, and it was found that compound 8 had good binding affinity to MRTF-A complex and Bcl-2. Through animal experiments, it was found that compound 8 could significantly improve the pathological damage of brain tissue after ischemia and could increase the expression of MRTF-A and Bcl-2 in cerebral cortex in rats. These results suggest that compound 8 may have a good inhibitory effect on apoptosis and tissue structurel disorders induced by cerebral ischemia-reperfusion, so as to reduce the injury caused by ischemic stroke.


Subject(s)
Neuroprotective Agents , Stroke , Rats , Animals , Molecular Structure , Proto-Oncogene Proteins c-bcl-2 , Stroke/drug therapy , Neuroprotective Agents/pharmacology
8.
China Pharmacy ; (12): 724-729, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-965513

ABSTRACT

OBJECTIVE To evaluate the clinical effectiveness and safety of domestic generic and imported original clopidogrel for antiplatelet therapy in patients with acute coronary syndrome (ACS). METHODS The clinical data of ACS patients in Nanjing Drum Tower Hospital of China Pharmaceutical University from January 2020 to June 2021 were retrospectively collected by using electronic medical record system, and the patients were divided into original drug group (321 cases) and generic drug group (328 cases) according to the drug use. Both groups were given dual antiplatelet therapy with clopidogrel and aspirin. The effectiveness and safety outcomes of the two groups were followed up for 12 months and compared, the related influential factors were analyzed. RESULTS Major adverse cardiovascular events (MACE) occurred in 16 and 22 patients in original drug group and generic drug group respectively, including nonfatal myocardial infarction (4 and 5 cases), stroke (2 and 4 cases), revascularization (8 and 3 cases), cardiovascular related death (2 and 4 cases), and all-cause death (4 and 6 cases). There were 12 and 7 patients with major bleeding events, 38 and 29 patients with minor bleeding events, and 33 and 21 patients with non-bleeding adverse events. There was no statistically significant difference in the cumulative incidence of related events (P values of Log-Rank tests were all greater than 0.05). Cox regression analysis showed that the use of generic clopidogrel did not increase the risk of MACE and major bleeding events in ACS patients [hazard ratio of 1.305 and 0.416, 95% confidence interval of (0.678, 2.512) and (0.155, 1.117), respectively, P>0.05], and the combination of proton pump inhibitors (PPI) could reduce the risk of major bleeding events [hazard ratio of 0.196, 95% confidence interval of (0.063, 0.611), P<0.05]. CONCLUSIONS Compared with imported original drug, domestic generic clopidogrel has similar clinical effectiveness and good safety. Combined use of PPI may be a beneficial factor to reduce the occurrence of major bleeding events in patients.

9.
Fitoterapia ; 161: 105256, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35870664

ABSTRACT

Six new sugar esters (1-6), named tenuifolisides F-G (1-2) and tenuifolioses W-Z (3-6), together with 16 known compounds (7-22) were isolated from the roots of Polygala tenuifolia. The chemical structures of the new compounds were elucidated by 1D, 2D NMR and HRESIMS techniques together with chemical methods. All the compounds were evaluated for the cytoprotective activity against hydrogen peroxide (H2O2)-induced oxidative stress in human keratinocyte HaCaT cells. Compounds 4, 5, 13, 20 and 22 showed strong cytoprotective effect.


Subject(s)
Polygala , Xanthones , Humans , Hydrogen Peroxide/analysis , Molecular Structure , Plant Roots/chemistry , Polygala/chemistry , Sugars/analysis , Xanthones/chemistry
10.
Hum Exp Toxicol ; 41: 9603271221108320, 2022.
Article in English | MEDLINE | ID: mdl-35722787

ABSTRACT

Chlorpromazine hydrochloride (CH) and N-acetyl-p-amino-phenoltriptolide (APAP) are typical acentral dopamine receptor antagonists and antipyretic analgesics in clinical applications, respectively. However, it has been reported that these 2 drugs could cause liver damage. Lysophosphatidylcholines (LPCs) have multiple physiological functions and are metabolized primarily in the liver, where it undergoes significant changes when the liver is damaged. In the study, 15 LPCs in the rat serum with CH- and APAP-induced liver injury were quantified based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry, and multivariate statistical analyses including principal component analysis (PCA) and orthogonal partial least squares discriminate analysis (OPLS-DA) were combined to understand CH- and APAP-induced liver injury from the perspective of LPC metabolic profiling. The quantitative results showed that there were significant changes in 10 LPCs and 5 LPCs after CH- and APAP-administration, separately. The results of PCA and OPLS-DA indicated that CH- and APAP-induced liver injury could be well distinguished by the LPC metabolic profiling, and 7 LPCs and 1 LPC biomarkers that could characterize CH- and APAP-induced liver damage in turn had been screened. This study will not only provide a new perspective for the clinical diagnosis of CH- and APAP-induced liver injury, but also offer a reference for further study of their hepatotoxicity mechanisms.


Subject(s)
Chemical and Drug Induced Liver Injury, Chronic , Lysophosphatidylcholines , Animals , Rats , Biomarkers , Chlorpromazine/toxicity , Chromatography, High Pressure Liquid/methods , Chromatography, Liquid , Mass Spectrometry/methods , Metabolomics/methods
11.
Korean J Physiol Pharmacol ; 26(3): 145-155, 2022 May 01.
Article in English | MEDLINE | ID: mdl-35477542

ABSTRACT

Multidrug resistance of tumors has been a severe obstacle to the success of cancer chemotherapy. The study wants to investigate the reversal effects of imperatorin (IMP) on doxorubicin (DOX) resistance in K562/DOX leukemia cells, A2780/Taxol cells and in NOD/SCID mice, to explore the possible molecular mechanisms. K562/DOX and A2780/Taxol cells were treated with various concentrations of DOX and Taol with or without different concentrations of IMP, respectively. K562/DOX xenograft model was used to assess anti-tumor effect of IMP combined with DOX. MTT assay, Rhodamine 123 efflux assay, RT-PCR, and Western blot analysis were determined in vivo and in vitro. Results showed that IMP significantly enhanced the cytotoxicity of DOX and Taxol toward corresponding resistance cells. In vivo results illustrated both the tumor volume and tumor weight were significantly decreased after 2-week treatment with IMP combined with DOX compared to the DOX alone group. Western blotting and RT-PCR analyses indicated that IMP downregulated the expression of P-gp in K562/DOX xenograft tumors in NOD/SCID mice. We also evaluated glycolysis and glutamine metabolism in K562/DOX cells by measuring glucose consumption and lactate production. The results revealed that IMP could significantly reduce the glucose consumption and lactate production of K562/DOX cells. Furthermore, IMP could also remarkably repress the glutamine consumption, α-KG and ATP production of K562/DOX cells. Thus, IMP may sensitize K562/DOX cells to DOX and enhance the anti-tumor effect of DOX in K562/DOX xenograft tumors in NOD/SCID mice. IMP may be an adjuvant therapy to mitigate the multidrug resistance in leukemia chemotherapy.

12.
Cryobiology ; 105: 50-55, 2022 04.
Article in English | MEDLINE | ID: mdl-34919943

ABSTRACT

Cryopreservation of testicular tissue from pre-pubertal boys before gonadotoxic treatment is an important step in fertility preservation. Yet, this approach remains experimental, and there is still few study measuring the effect of tissue size on the graft after cryopreservation and transplantation. The objective of this study is to detect the effect of varying tissue sizes on the efficacy of rat testicular tissue cryopreservation and transplantation. Varying sizes of rat testicular tissues were frozen-thawed and autografted. At the 30th day after grafting, the grafts were collected for histology assessment and immunohistochemistry assay for MAGE-A4 (germ cell marker) and CD34 (blood vessel marker). The transplant recovery, seminiferous tubule integrity, tubular diameter, spermatogonia number, and microsvessel density in testicular fragments sizing in 3 mm in length, 3 mm wide, and 3 mm in thickness were significantly lower than other groups. Whereas, the absorption rate of graft sizing in 1 mm in length, 1 mm in wide, and 1 mm in thickness was significantly higher than other groups. Testicular fragment sizing in 2-3 mm in length, 2-3 mm in wide, and 2 mm in thickness (8 mm3-18 mm3) is suitable for rat testicular tissue cryopreservation and transplantation.


Subject(s)
Cryopreservation , Fertility Preservation , Animals , Cryopreservation/methods , Humans , Immunohistochemistry , Male , Rats , Spermatogonia , Testis/transplantation
13.
Article in English | WPRIM (Western Pacific) | ID: wpr-927099

ABSTRACT

Multidrug resistance of tumors has been a severe obstacle to the success of cancer chemotherapy. The study wants to investigate the reversal effects of imperatorin (IMP) on doxorubicin (DOX) resistance in K562/DOX leukemia cells, A2780/Taxol cells and in NOD/SCID mice, to explore the possible molecular mechanisms. K562/ DOX and A2780/Taxol cells were treated with various concentrations of DOX and Taol with or without different concentrations of IMP, respectively. K562/DOX xenograft model was used to assess anti-tumor effect of IMP combined with DOX. MTT assay, Rhodamine 123 efflux assay, RT-PCR, and Western blot analysis were determined in vivo and in vitro. Results showed that IMP significantly enhanced the cytotoxicity of DOX and Taxol toward corresponding resistance cells. In vivo results illustrated both the tumor volume and tumor weight were significantly decreased after 2-week treatment with IMP combined with DOX compared to the DOX alone group. Western blotting and RT-PCR analyses indicated that IMP downregulated the expression of P-gp in K562/DOX xenograft tumors in NOD/SCID mice. We also evaluated glycolysis and glutamine metabolism in K562/DOX cells by measuring glucose consumption and lactate production. The results revealed that IMP could significantly reduce the glucose consumption and lactate production of K562/DOX cells. Furthermore, IMP could also remarkably repress the glutamine consumption, α-KG and ATP production of K562/DOX cells. Thus, IMP may sensitize K562/DOX cells to DOX and enhance the antitumor effect of DOX in K562/DOX xenograft tumors in NOD/SCID mice. IMP may be an adjuvant therapy to mitigate the multidrug resistance in leukemia chemotherapy.

14.
Angew Chem Int Ed Engl ; 60(51): 26806-26812, 2021 Dec 13.
Article in English | MEDLINE | ID: mdl-34582084

ABSTRACT

The performance of electrode material is correlated with the choice of electrolyte, however, how the solvation has significant impact on electrochemical behavior is underdeveloped. Herein, N-heteropentacenequinone (TAPQ) is investigated to reveal the solvation effect on the performance of sodium-ion batteries in different electrolyte environment. TAPQ cycled in diglyme-based electrolyte exhibits superior electrochemical performance, but experiences a rapid capacity fading in carbonate-based electrolyte. The function of solvation effect is mainly embodied in two aspects: one is the stabilization of anion intermediate via the compatibility of electrode and electrolyte, the other is the interfacial electrochemical characteristics influenced by solvation sheath structure. By revealing the failure mechanism, this work presents an avenue for better understanding electrochemical behavior and enhancing performance from the angle of solvation effect.

15.
Andrologia ; 53(11): e14223, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34423461

ABSTRACT

The objective of the present experiment was to explore the role of NLRP3 inflammasome in the testicular tissue freezing, thawing and grafting; furthermore, the potential effect of a NLRP3 inhibitor on the function of testis transplant was explored. Tissues from male Wistar rats in pre-pubertal age were cryopreserved, thawed and auto-transplanted into the scrotum treated or not treated with the MCC950 (a NLRP3 inhibitor). After grafting, cryopreserved tissue was removed and analysed. Quantitative morphometric, immunohistochemical techniques and Western blotting were used to evaluate the survival of spermatogonia and the activation of the NLRP3 inflammasome after freezing/thawing/grafting. Moreover, serum IL-1ß level was assessed with ELISA kits. The testicular transplants exhibited upregulated expression of the NLRP3 pathway meditors (NLRP3, IL-1ß). In NLRP3 inhibition group, the rate of recovered grafts, the percentage of intact tubules and spermatogonial number were significantly higher than that in cryopreserved graft group. Moreover, serum concentration of IL-1ß in NLRP3 inhibition group was significantly lower than that in cryopreserved graft group. Testicular tissue cryopreservation and transplantation exhibited upregulated expression of NLRP3 pathway and NLRP3 inflammasome blockade improves testicular graft function. These finding suggest that NLRP3 inflammasome is a therapeutic target for testicular tissue cryopreservation and transplantation.


Subject(s)
Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , Animals , Cryopreservation , Interleukin-1beta , Male , Rats , Rats, Wistar , Spermatogonia
16.
Andrologia ; 53(10): e14191, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34278587

ABSTRACT

The aim of this study is to do a study of cryoinjury and ischaemic injury on testicular graft during cryopreservation and transplantation. According to time at 1, 3, 7 and 14 days after transplantation, the grafts were collected for immunohistochemistry assay for CD34 (blood vessel marker), VEGF (neoangiogenesis marker), caspase-3 (apoptosis marker) MAGE-A4 (germ cell marker). A significant increase was observed in the density of VEGF-positive blood vessels on day 3, reached a peak on day 7. On post-transplant day 3, a sharp increase occurred in the rate of spermatogonia-expressing caspase-3 until the day 7. At 14th day after transplantation, the spermatogonia number per round tubule of nonfrozen grafts was 41 ± 5.9% from that of fresh control tissues, while, in frozen-thawed grafts, the spermatogonia number per round tubule was 36.8 ± 4.6% from that of fresh control tissues. In testicular grafts, angiogenesis initiated reperfusion from day 3, and the formation of new blood vessel generally is completed about 7 days after transplantation. Angiogenesis in grafts after transplantation plays a crucial role in the restoration of function. Therefore, minimising ischaemic injury as well as improvement of cryopreservation protocols are needed to improve testicular graft after freezing, thawing and grafting.


Subject(s)
Cryopreservation , Testis , Humans , Male , Spermatogonia
17.
J Recept Signal Transduct Res ; 41(4): 371-377, 2021 Aug.
Article in English | MEDLINE | ID: mdl-32896205

ABSTRACT

Transmembrane proteins (TMEMs), spanning the entire width of lipid bilayers and anchored to them permanently, exist in diverse cell types to implement a series of essential physiological functions. Recently, TMEM48, a member of the TMEM family, has been demonstrated to be closely associated with tumorigenesis. However, little is known about the specific role of TMEM48 in cervical cancer (CC). This study aimed to investigate the biological functions of TMEM48 in CC. The CCK-8 assay was performed to detect CC cell proliferation. The wound healing and transwell assays were conducted to measure cell migration and invasion, respectively. The levels of TMEM48, ß-catenin, T cell factor 1(TCF1) and axis formation inhibitor 2 (AXIN2) were examined by the western blot analysis. Xenograft models were established for the tumorigenesis assay in vivo. The results showed that TMEM48 was overexpressed in CC tissues and cell lines. Knockdown of TMEM48 significantly inhibited CC cell proliferation, migration and invasion in vitro and suppressed CC cell growth in vivo. In addition, the investigation on the molecular mechanisms indicated that TMEM48 down-regulation remarkably decreased the protein levels of ß-catenin, TCF1 and AXIN2 in CC cells and TMEM48 exerted its promoting effect on CC progression via activation of the Wnt/ß-catenin pathway. Taken together, our study suggested TMEM48 as a promising therapeutic target for CC treatment.


Subject(s)
Gene Expression Regulation, Neoplastic , Nuclear Pore Complex Proteins/biosynthesis , Uterine Cervical Neoplasms/metabolism , Wnt Proteins/metabolism , beta Catenin/metabolism , Animals , Axin Protein/biosynthesis , Axin Protein/metabolism , Cell Movement , Cell Proliferation , Disease Progression , Female , HeLa Cells , Hepatocyte Nuclear Factor 1-alpha/biosynthesis , Hepatocyte Nuclear Factor 1-alpha/metabolism , Humans , Immunohistochemistry , Lipid Bilayers , Mice , Mice, Inbred BALB C , Neoplasm Transplantation , Wound Healing
18.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-906412

ABSTRACT

Liver, as a critical organ of metabolism and detoxification, can be damaged by viral infection, drug abuse, and heavy drinking. Liver diseases pose a serious threat to people's health and life in China.At present, drug therapy has been primarily adopted clinically in the treatment of the liver injury.In-depth investigation of the mechanism of liver-protective drugs is of great significance to the prevention and treatment of clinical liver diseases.In recent years, with the development of the medical industry in China, an increasing number of studies have focused on the treatment of liver injury with Chinese medicine.Compared with western medicine, Chinese medicine is advantageous in few side effects and overall regulation, which plays a pivotal role in liver protection.However, its underlying mechanism in liver protection still needs to be further studied due to its complex compositions and diverse targets.Metabolomics, a new approach to studying the metabolic pathway of biological systems, provides integral and systematic views in the investigation of liver protection with Chinese medicine. By virtue of metabolomics, the mechanism of Chinese medicine in multi-target and multi-pathway liver protection can be analyzed comprehensively, and the corresponding biomarkers can also be screened out. The authors analyzed the studies of the treatment of chemical liver injury models induced by carbon tetrachloride (CCl4), dimethylnitrosamine (DMN), α-naphthyl isothiocyanate (ANIT), and alcohol by Chinese medicinal compounds, single herbal medicines, and monomers of Chinese medicine based on metabolomics, and summarized the biomarkers and related metabolic pathways of Chinese medicine in the intervention of each type of liver injury, aiming at providing a reference for the further research and clinical application in the treatment of different types of liver injuries by Chinese medicine.

19.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1014285

ABSTRACT

Liver disease is a kind of common and frequently occurring disease, which seriously threatens human life and health. The study of liver disease has become a hotspot and difficulty in the field of organic diseases. In recent years, scholars have found a close relation between liver disease and the metabolism of lipid compounds in body. Lipomics, an important branch of metabolomics, can evaluate liver diseases by analyzing the level of lipid changes in the body, find biomarkers of liver diseases, and study the possible mechanism of liver diseases. It plays an important role in the study of liver diseases. In order to provide reference for further study of liver diseases and their clinical treatment, the research methods of lipomics have been reviewed, and the application of lipomics in liver diseases summarized and analyzed based on different types of liver diseases in this paper.

20.
Andrology ; 8(1): 110-116, 2020 01.
Article in English | MEDLINE | ID: mdl-31127676

ABSTRACT

BACKGROUND: It has been reported that paternal folic acid deficiency is correlated with male infertility and increased birth defects in the offspring. However, there are few data concerning the influence of folic acid supplementation on male-factor infertility with MTHFR gene polymorphisms. OBJECTIVES: To evaluate whether folic acid supplementation has a beneficial effect on oligozoospermia with MTHFR gene polymorphisms in Chinese infertility population. MATERIALS AND METHODS: The infertile men suffering oligozoospermia with MTHFR gene polymorphisms were randomly divided into the folic acid treatment groups receiving folic acid 0.8 mg daily for 3 months and the placebo groups receiving placebo for 3 months. Semen parameters, seminal MDA, and DNA fragmentation were measured. Furthermore, spontaneous pregnancy rate and live birth rate were evaluated. RESULTS: Administration of folic acid for 3 months could significantly improve the seminal parameters in patients with MTHFR 677 TT genotype in comparison with that receiving placebo. Moreover, seminal MDA and sperm DNA fragmentation index in patients with MTHFR 677 TT genotype significantly declined at the end of treatment. Spontaneous pregnancy rate and live birth rate tended to be significantly higher in couples in which the men with MTHFR 677 TT genotype receiving folic acid than that receiving placebo. However, folic acid treatment did not exhibit any advantage in MTHFR 677 CT, 1298 AC, 1298 CC, 1793 GA, or combined 677 CT/1298 AC genotype. DISCUSSION: The anti-oxidation function of folic acid is one of possible mechanisms invovled in improving seminal parameters and pregnancy outcome. CONCLUSIONS: Folic acid supplementation has a beneficial effect on oligozoospermia with MTHFR 677 TT genotype in term of seminal parameters, seminal MDA, sperm DNA fragmentation, and pregnancy outcome.


Subject(s)
DNA Fragmentation/drug effects , Folic Acid/therapeutic use , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Oligospermia/drug therapy , Vitamin B Complex/therapeutic use , Adult , Double-Blind Method , Female , Folic Acid/pharmacology , Humans , Male , Middle Aged , Oligospermia/genetics , Pharmacogenomic Variants , Pregnancy , Pregnancy Rate , Semen Analysis , Vitamin B Complex/pharmacology , Young Adult
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