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1.
Indian J Hematol Blood Transfus ; 40(2): 220-230, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38708154

ABSTRACT

Despite being the most common primary tumor of the spleen, in the past, few studies have predicted the prognosis of primary spleen diffuse large B cell lymphoma. This study aimed to establish a nomogram prediction model of overall survival in primary DLBCL of the spleen. We screened out 347 patients with primary splenic DLBCL from surveillance, epidemiology, and end results database. According to the Cox regression results (age, Ann Arbor Stage, splenectomy and chemotherapy was the independent risk factor for primary splenic DLBCL), the nomogram was constructed. We evaluated the predictive ability of nomogram with C-Index (training cohort: 0.719 [0.669-0.769]; validation cohort: 0.711 [0.641-0.781]) and 3-year/5-year receiver operating characteristic area under curve (3-year/5-year ROCAUC, training cohort: 0.731/0.742; validation cohort: 0.721/0.742). Calibratioin plot shows that our predicted values fluctuate around the actual value, indicating good agreement with nomogram. The decision curve analysis (DCA) results showed that our nomogram could benefit more than Ann Arbor Stage for predicts the prognosis of the primary splenic DLBCL. The Kaplan-Meier and landmark analysis showed that a great discrimination between high-risk group and low-risk group (P < 0.05) and indicating that our nomogram has the good ability to identify high-risk patients. In this study, a nomogram prediction model for primary spleen DLBCL was established, which has good ability of prediction and generalization. It can help clinicians carry out individualized treatment measures.

4.
J Biochem Mol Toxicol ; 38(3): e23669, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38459698

ABSTRACT

Paclitaxel (PTX) is a chemotherapeutic agent that is widely used for the treatment of several types of tumors. However, PTX-induced peripheral neuropathy (PIPN) is an adverse effect generally induced by long-term PTX use that significantly impairs the quality of life. Necroptosis has been implicated in various neurodegenerative disorders. Necroptosis of dorsal root ganglion neurons triggers the pathogenesis of PIPN. Therefore, the present study aims to investigate the role of spinal neuronal necroptosis in PIPN. It also explores the potential role of microglial polarization in necroptosis. We established rat models of PIPN via quartic PTX administration on alternate days (accumulated dose: 8 mg/kg). PTX induced obvious neuronal necroptosis and upregulated the expression of receptor-interacting protein kinase (RIP3) and mixed lineage kinase domain-like protein (MLKL) in the spinal dorsal horn. These effects were inhibited with a necroptosis pathway inhibitor, necrostatin-1 (Nec-1). The effect of microglial polarization on the regulation of spinal necroptosis was elucidated by administering minocycline to inhibit PTX-induced M1 polarization of spinal microglia caused by PTX. We observed a significant inhibitory effect of minocycline on PTX-induced necroptosis in spinal cord cells, based on the downregulation of RIP3 and MLKL expression, and suppression of tumor necrosis factor-α and IL-ß synthesis. Additionally, minocycline improved hyperalgesia symptoms in PIPN rats. Overall, this study suggests that PTX-induced polarization of spinal microglia leads to RIP3/MLKL-regulated necroptosis, resulting in PIPN. These findings suggest a potential target for the prevention and treatment of neuropathic pain.


Subject(s)
Neuralgia , Paclitaxel , Rats , Animals , Paclitaxel/adverse effects , Microglia/pathology , Necroptosis , Minocycline/adverse effects , Quality of Life , Neuralgia/chemically induced
5.
ACS Appl Mater Interfaces ; 16(13): 16011-16028, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38529951

ABSTRACT

Superbug infections and transmission have become major challenges in the contemporary medical field. The development of novel antibacterial strategies to efficiently treat bacterial infections and conquer the problem of antimicrobial resistance (AMR) is extremely important. In this paper, a bimetallic CuCo-doped nitrogen-carbon nanozyme-functionalized hydrogel (CuCo/NC-HG) has been successfully constructed. It exhibits photoresponsive-enhanced enzymatic effects under near-infrared (NIR) irradiation (808 nm) with strong peroxidase (POD)-like and oxidase (OXD)-like activities. Upon NIR irradiation, CuCo/NC-HG possesses photodynamic activity for producing singlet oxygen(1O2), and it also has a high photothermal conversion effect, which not only facilitates the elimination of bacteria but also improves the efficiency of reactive oxygen species (ROS) production and accelerates the consumption of GSH. CuCo/NC-HG shows a lower hemolytic rate and better cytocompatibility than CuCo/NC and possesses a positive charge and macroporous skeleton for restricting negatively charged bacteria in the range of ROS destruction, strengthening the antibacterial efficiency. Comparatively, CuCo/NC and CuCo/NC-HG have stronger bactericidal ability against methicillin-resistant Staphylococcus aureus (MRSA) and ampicillin-resistant Escherichia coli (AmprE. coli) through destroying the cell membranes with a negligible occurrence of AMR. More importantly, CuCo/NC-HG plus NIR irradiation can exhibit satisfactory bactericidal performance in the absence of H2O2, avoiding the toxicity from high-concentration H2O2. In vivo evaluation has been conducted using a mouse wound infection model and histological analyses, and the results show that CuCo/NC-HG upon NIR irradiation can efficiently suppress bacterial infections and promote wound healing, without causing inflammation and tissue adhesions.


Subject(s)
Bacterial Infections , Methicillin-Resistant Staphylococcus aureus , Animals , Hydrogels/pharmacology , Escherichia coli , Hydrogen Peroxide , Reactive Oxygen Species , Phototherapy , Bacterial Infections/drug therapy , Anti-Bacterial Agents/pharmacology , Carbon , Disease Models, Animal , Nitrogen
6.
World J Hepatol ; 16(2): 229-240, 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38495269

ABSTRACT

BACKGROUND: Echinococcosis is prevalent in 9 provinces in Western and Northern China. An epidemiological survey of echinococcosis in 2012 and 2016 showed cases of echinococcosis in Yunnan Province. AIM: To understand the spatial distribution and epidemiological characteristics of echinococcosis in Yunnan for the prevention and control of echinococcosis and to reduce the risk of infection in Yunnan Province. METHODS: Based on the China Information System for Disease Control and Prevention (CISDCP), echinococcosis cases reported from 36 hospitals and 34 Centers for Disease Control were investigated and epidemiologically analyzed from 2021 to 2022. The exclusion criteria included suspected cases, same case only counted once and cases not from Yunnan. A total of 705 cases were investigated, of which 397 cases were suitable for statistical analysis. In these 397 cases, epidemiological investigation was tracked in 187 cases. All data were inputted using double entry in the Excel database, with error correction by double-entry comparison. The data on echinococcosis cases in Yunnan Province were analyzed by ArcGIS 10.1 software to generate a density map of echinococcosis distribution. All statistical analyses were conducted using SPSS 17.0, including the chi-square test, linear regression test and logistic univariate and multivariate regression analyses. RESULTS: A total of 397 cases were found in 89 counties in Yunnan Province. The number of cases in the top three prefectures were Dali (38.1%), Diqing (10.1%), and Kunming (8.3%), and the top five counties were Jianchuan (9.1%), Shangri La (8.3%), Eryuan (7. 6%), Heqing (6.9%), and Dali Districts (5.0%). There were significant differences between the different areas. The case reporting rate by CISDCP (33.8%) was low; the first case was reported by CISDCP in 2002, and the highest number of cases was 50 (2017). Confirmed and clinical cases accounted for 62.5% and 37.5%, respectively. However, 90.9% of the cases of hydatid disease were reported by the hospital system, and only 9.1% of the cases of hydatid disease were found in the community through active screening. The difference between the two methods of case detection was statistically significant. Most of the cases of echinococcosis were found in farmers/herdsmen (75.1%) and students (9.1%). In addition, Han (43.6%) and Bai (26.2%) had a higher incidence of infection than other nationalities, and the liver (87.7%) and lung (6.8%) were the most common sites of cyst formation. Among the analyzed cases, 187 were epidemiologically analyzed and the clinical symptoms were not obvious in the early stage in 47.1% of cases. The results of logistic regression analysis showed that the age group, education level, presence of dogs in the family (either previously or currently), and handwashing (occasionally or not) were factors related to echinococcosis infection. 55.6% of cases were in endemic areas, and 44.4% of cases were in non-endemic areas. Among 83 cases in non-endemic areas, only 4 cases had been to endemic areas and had a history of living, working, travelling, or hunting in echinococcosis epidemic areas. CONCLUSION: Cases of echinococcosis were reported throughout the entire Yunnan province, with the majority distributed in Western Yunnan, suggesting that echinococcosis control should be strengthened in this area. We suggest that an epidemiological investigation should be carried out in the future, based on the clues from newly discovered cases in hospitals or from the CISDCP. The newly discovered cases in the hospital provided clues to comprehensively determine the location of cases and where epidemic spot investigation should be conducted.

7.
Biochem Genet ; 2024 Jan 21.
Article in English | MEDLINE | ID: mdl-38245888

ABSTRACT

Hepatocellular carcinoma (HCC) represents an estrogen-dependent tumor. The action of estrogen is regulated via estrogen receptor (ER). Polymorphisms in ERα gene, ESR1, are known to be related to HCC susceptibility among people carrying chronic hepatitis B (CHB). But the effect of ERß on HCC is still largely unclear, and studies about the genetic variability of ESR2 and HCC are rare. For understanding ESR2's effect on HCC, this work tested two polymorphisms in the ESR2 gene promoter as well as the associations with CHB, HCC, and hepatitis B virus (HBV)-related liver cirrhosis (LC) among the Guangxi population. This work enrolled a total of 137 CHB, 136 LC, and 149 HBV-related HCC patients, together with 146 normal subjects. ESR2 polymorphisms rs3020449 and rs2978381 were examined using the SNaPshot genotyping technique. The AG genotype and dominant model of rs3020449 were related to the decreased CHB susceptibility. In both the overall and subgroup analyses, no associations were observed with the remaining models in all patient groups (those with CHB, HBV-related LC, and HCC), but associations were found between the dominant (TC+CC vs TT) and allele models (C vs T) of rs2978381 and increased HBV-related LC and HCC susceptibility, but not CHB. These findings suggest that rs3020449 polymorphism of ESR2 gene makes great contribution to the decreased CHB risk and that rs2978381 significantly contributed to higher risks of HBV-related LC and HCC.

8.
Plant Biotechnol J ; 22(6): 1504-1515, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38206288

ABSTRACT

Professor Rajeev K. Varshney's transformative impact on crop genomics, genetics, and agriculture is the result of his passion, dedication, and unyielding commitment to harnessing the potential of genomics to address the most pressing challenges faced by the global agricultural community. Starting from a small town in India and reaching the global stage, Professor Varshney's academic and professional trajectory has inspired many scientists active in research today. His ground-breaking work, especially his effort to list orphan tropical crops to genomic resource-rich entities, has been transformative. Beyond his scientific achievements, Professor Varshney is recognized by his colleagues as an exemplary mentor, fostering the growth of future researchers, building institutional capacity, and strengthening scientific capability. His focus on translational genomics and strengthening seed system in developing countries for the improvement of agriculture has made a tangible impact on farmers' lives. His skills have been best utilized in roles at leading research centres where he has applied his expertise to deliver a new vision for crop improvement. These efforts have now been recognized by the Royal Society with the award of the Fellowship (FRS). As we mark this significant milestone in his career, we not only celebrate Professor Varshney's accomplishments but also his wider contributions that continue to transform the agricultural landscape.


Subject(s)
Crops, Agricultural , Genomics , Portraits as Topic , Agriculture/history , Crops, Agricultural/genetics , Genomics/history , History, 20th Century , History, 21st Century , Portraits as Topic , Societies, Scientific/organization & administration
9.
Medicine (Baltimore) ; 103(4): e36859, 2024 Jan 26.
Article in English | MEDLINE | ID: mdl-38277570

ABSTRACT

BACKGROUND: Laparoscopic total mesorectal excision (LaTME) and transanal total mesorectal excision (TaTME) are popular mid and low rectal cancer trends. However, there is currently no systematic comparison between LaTME and TaTME of mid and low rectal cancer. Therefore, we systematically study the perioperative and pathological outcomes of LaTME and TaTME in mid and low rectal cancer. METHODS: Articles included searching through the Embase, Cochrane Library, PubMed, Medline, and Web of science for articles on LaTME and TaTME. We calculated pooled standard mean difference (SMD), relative risk (RR), and 95% confidence intervals (CIs). The protocol for this review has been registered on PROSPERO (CRD42022380067). RESULTS: There are 8761 participants included in 33 articles. Compared with TaTME, patients who underwent LaTME had no statistical difference in operation time (OP), estimated blood loss (EBL), postoperative hospital stay, over complications, intraoperative complications, postoperative complications, anastomotic stenosis, wound infection, circumferential resection margin, distal resection margin, major low anterior resection syndrom, lymph node yield, loop ileostomy, and diverting ileostomy. There are similarities between LaTME and TaTME for 2-year DFS rate, 2-year OS rate, distant metastasis rat, and local recurrence rate. However, patients who underwent LaTME had less anastomotic leak rates (RR 0.82; 95% CI: 0.70-0.97; I2 = 10.6%, P = .019) but TaTME had less end colostomy (RR 1.96; 95% CI: 1.19-3.23; I2 = 0%, P = .008). CONCLUSION: This study comprehensively and systematically evaluated the differences in safety and effectiveness between LaTME and TaTME in the treatment of mid and low rectal cancer through meta-analysis. Patients who underwent LaTME had less anastomotic leak rate but TaTME had less end colostomy. There is no difference in other aspects. Of course, in the future, more scientific and rigorous conclusions need to be drawn from multi-center RCT research.


Subject(s)
Laparoscopy , Rectal Neoplasms , Transanal Endoscopic Surgery , Humans , Animals , Rats , Rectum/surgery , Rectum/pathology , Anastomotic Leak/epidemiology , Anastomotic Leak/etiology , Anastomotic Leak/surgery , Margins of Excision , Transanal Endoscopic Surgery/adverse effects , Transanal Endoscopic Surgery/methods , Rectal Neoplasms/pathology , Laparoscopy/adverse effects , Laparoscopy/methods , Postoperative Complications/etiology , Treatment Outcome
10.
Int J Biol Macromol ; 257(Pt 1): 128615, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38070798

ABSTRACT

Nowadays, highly toxic antimony has severely posed threat to water sources and jeopardized human health. Fabricating adsorbents with the capability of easy separation, high efficiency and large adsorption capacity remains a major challenge. In this paper, zirconium functionalized chitosan melamine foam (ZCMF) was fabricated with zirconium and chitosan crosslinked onto melamine foam, then utilized for the removal of antimony(III/V) in water. The characterization of SEM and EDS collectively showed that ZCMF has a porous structure which could boost the mass transfer rate and zirconium ions on the surface could provide plentiful active adsorption sites. Systematic adsorption experiments demonstrated that the experimental data of Sb(III) and Sb(V) were consistent with the pseudo-second-order and Elovich kinetic models, respectively, and the Langmuir maximum adsorption capacities were separately 255.35 mg g-1 (Sb(III)) and 414.41 mg g-1 (Sb(V)), which displayed prominent performance among adsorbents derived from biomass. Combining the XPS and FTIR characterization with experimental data, it is rational to speculate that ZCMF could remove Sb from aqueous solution through ligand exchange, electrostatic attraction, and surface complexation mechanisms. ZCMF exhibited excellent performance, including large adsorption capacity, easy separation, facile preparation and eco-friendliness. It could be a promising new adsorbent for the treatment of antimony-containing wastewater.


Subject(s)
Chitosan , Triazines , Water Pollutants, Chemical , Humans , Antimony/chemistry , Zirconium/chemistry , Water , Adsorption , Water Pollutants, Chemical/chemistry , Kinetics
11.
Plant Genome ; 17(1): e20333, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37122200

ABSTRACT

Terminal drought is one of the major constraints to crop production in chickpea (Cicer arietinum L.). In order to map drought tolerance related traits at high resolution, we sequenced multi-parent advanced generation intercross (MAGIC) population using whole genome resequencing approach and phenotyped it under drought stress environments for two consecutive years (2013-14 and 2014-15). A total of 52.02 billion clean reads containing 4.67 TB clean data were generated on the 1136 MAGIC lines and eight parental lines. Alignment of clean data on to the reference genome enabled identification of a total, 932,172 of SNPs, 35,973 insertions, and 35,726 deletions among the parental lines. A high-density genetic map was constructed using 57,180 SNPs spanning a map distance of 1606.69 cM. Using compressed mixed linear model, genome-wide association study (GWAS) enabled us to identify 737 markers significantly associated with days to 50% flowering, days to maturity, plant height, 100 seed weight, biomass, and harvest index. In addition to the GWAS approach, an identity-by-descent (IBD)-based mixed model approach was used to map quantitative trait loci (QTLs). The IBD-based mixed model approach detected major QTLs that were comparable to those from the GWAS analysis as well as some exclusive QTLs with smaller effects. The candidate genes like FRIGIDA and CaTIFY4b can be used for enhancing drought tolerance in chickpea. The genomic resources, genetic map, marker-trait associations, and QTLs identified in the study are valuable resources for the chickpea community for developing climate resilient chickpeas.


Subject(s)
Cicer , Chromosome Mapping , Cicer/genetics , Genome, Plant , Genome-Wide Association Study , Drought Resistance
12.
JOURNAL OF RARE DISEASES ; (4): 108-113, 2024.
Article in English | WPRIM (Western Pacific) | ID: wpr-1006905

ABSTRACT

We studied the patients diagnosed with X-linked hypophosphatemicrickets(XLH) and treated with burosumab in Peking Union Medical College Hospital from January 2021 to December 2022. In addition, we described the clinical characteristics of the patients, the changes of clinical indexes before and after burosumab treatment, and the adverse drug reactions during treatment. We also evaluated the efficacy and safety of burosumab for XLH. The results showed that three children XLH patients and one adult XLH patients received burosumab treatment. After treatment, the serum phosphorus level of all patients increased; the serum phosphorus of 3 children patients increased above the lower limit of the reference value range; the serum alkaline phosphatase(ALP) of all patients was lower than that of before treatment; the serum ALP of one adult patient was close to the normal range after 2.5 years of treatment. One child patient showed small crystals in kidney through ultrasound 48 weeks after treatment; one child and one adult showed increased serum parathyroid hormone(PTH)level before treatment and serum PTH continued increasing after treatment. Finally, it may be concluded that burosumab increased serum phosphorus levels in XLH patients, kept the level relatively stable, and reduced serum ALP levels. No serious adverse reactions occurred during treatment, in order to provide reference for the use of burosumab in patients with XLH.

13.
China Pharmacy ; (12): 192-197, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1006177

ABSTRACT

OBJECTIVE To investigate the effects of anlotinib on the malignant phenotype of glioma cells by regulating the nuclear factor-κB (NF-κB) signaling pathway. METHODS Human glioma T98G cells were cultured in vitro, and 5-fluorouracil was used as positive control to investigate the effects of different concentrations of anlotinib (5, 10, 20 μmol/L) on the ability of proliferation, adhesion, migration and invasion, the expressions of epithelial-mesenchymal transition (EMT) related proteins [E-cadherin, N-cadherin, vimentin and fibronectin (FN)]. NF- κB signaling pathway inhibitor (BAY 11-7082) and activator (prostratin) were additionally used to verify the possible mechanism of the above effects of anlotinib. RESULTS Anlotinib with 5, 10, 20 μmol/L could significantly decrease the activity of cell proliferation (except for 5 μmol/L anlotinib group), migration rate, and the number of adherent cells and invasive cells, could significantly up-regulate the expression of E-cadherin protein while down-regulate the expressions of N-cadherin, vimentin and FN protein (P<0.05); the effect of 20 μmol/L anlotinib was similar to that of positive control (P>0.05). Compared with 10 μmol/L anlotinib, pathway inhibitor could significantly decrease the ability of proliferation, adhesion, migration and invasion, and the expressions of N-cadherin, vimentin, FN and phosphorylated NF-κB p65 protein, while could significantly up-regulate the expression of E-cadherin protein (P<0.05); above indexes were reversed significantly by pathway activator (P<0.05). CONCLUSIONS Anlotinib may inhibit the proliferation, adhesion, migration and invasion of human glioma T98G cells, which may be associated with the inhibition of the NF-κB signaling pathway, thus inhibiting cell EMT-like processes.

14.
International Eye Science ; (12): 225-229, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1005385

ABSTRACT

Transient receptor potential vanilloid receptor 4(TRPV4)is a non-selective cation channel responsible for sensing changes in cell swelling, temperature, mechanical stretch, shear stress and osmotic pressure by regulating transmembrane calcium signaling and thereby influencing gene expression, cell morphology, and cytoskeletal construction. TRPV4 is widely expressed throughout the body. Intraocularly, TRPV4 is functionally expressed in the cornea, lens, ciliary body, trabecular meshwork and retina. In this article, the expression and physiopathological functions of TRPV4 in various tissues of the eye were described. With the in-depth study of TRPV4 in ocular pathophysiological functions, TRPV4 may become a potential drug target in corneal injury repair, glaucoma and retinal angiogenesis, but further in-depth study is still needed.

15.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1003427

ABSTRACT

Reflux esophagitis is an inflammatory disease of esophageal mucosa damage caused by the reflux of gastric contents into the esophagus. Its incidence is on the rise, and it has become an important precancerous disease of esophageal cancer. Studies have shown that the continuous inflammatory response stimulates the esophageal mucosa, causing abnormal proliferation of esophageal epithelial cells and damage to esophageal mucosal tissue, which eventually leads to the occurrence of heterogeneous hyperplasia and even carcinogenesis. The nuclear transcription factor-kappa B (NF-κB) signaling pathway is one of the most classical inflammatory and cancer signaling pathways. It has been found that abnormal activation of the NF-κB signaling pathway is crucial to the development and prognosis of reflux esophagitis and esophageal cancer. It is widely involved in the proliferation, autophagy, apoptosis, and inflammatory response of esophageal epithelial cells and tumor cells, accelerating the transformation of reflux esophagitis to esophageal cancer and making it a potential target for the treatment of reflux esophagitis and esophageal cancer. Currently, there is no specific treatment for reflux esophagitis and esophageal cancer, and large side effects often appear. Therefore, finding a promising and safe drug remains a top priority. In recent years, traditional Chinese medicine scholars have conducted a lot of research on NF-κB signaling pathway, and the results indicate that NF-κB signaling pathway is an important potential target for traditional Chinese medicine to prevent and treat reflux esophagitis and esophageal cancer, but there is a lack of comprehensive and systematic elaboration. Therefore, this paper summarized the relevant studies in recent years, analyzed the relationship among NF-κB signaling pathway, reflux esophagitis, esophageal cancer, and transformation from inflammation to cancer, and reviewed the research literature on the regulation of the NF-κB signaling pathway in traditional Chinese medicine to prevent and treat reflux esophagitis and esophageal cancer, so as to provide new ideas for the prevention and treatment of reflux esophagitis and esophageal cancer.

16.
China Pharmacy ; (12): 1016-1022, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1016729

ABSTRACT

Esophageal cancer (EC) is a common malignant tumor of the digestive system with an extremely poor prognosis. MicroRNA (miRNA) is an important regulator in tumor occurrence and development, and can participate in malignant biological behaviors such as tumor cell proliferation, invasion, metastasis and apoptosis. Traditional Chinese medicine has the characteristics of accurate curative effects, wide range of effects, and few side effects. The review uses miRNA as the entry point to systematically elaborate on the mechanism of traditional Chinese medicine-mediated miRNA intervening in EC. The results showed that active ingredients of traditional Chinese medicine (including curcumin, Tussilago farfara polysaccharides, Atractylodes macrocephala polysaccharides and ophiopogonin B) and Dougen guanshitong oral liquid could up-regulate the expressions of miRNAs such as miRNA-532-3p (miR-532-3p), miR-551b-3p, miR-99a, miR-34a, miR-199a-3p and miR-377; and the active ingredients/parts of traditional Chinese medicine (including chrysin and Actinidia arguta extract), and Chinese herbal formulas (including Chaihu shugan san combined with Xuanfu daizhe decoction and Modified jupi zhuru decoction) could down-regulate the expressions of miRNAs such as miR-199a-3p, miR-451 and miR-21, which could regulate the expressions of signaling pathways (phosphoinositide 3-kinase/protein kinase B, etc.) or their downstream protein(zinc-finger and homeobox protein 1, etc.) or enzymes(thymidine kinase-1, etc.), inhibit the proliferation, invasion and metastasis of EC cells and induce apoptosis, thereby ultimately achieving the purpose of preventing the disease from aggravating.

17.
Acta Pharmaceutica Sinica ; (12): 374-381, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1016650

ABSTRACT

This study aims to investigate the effect of salvianolic acid B (Sal B), the active ingredient of Salvia miltiorrhiza, on H9C2 cardiomyocytes injured by oxygen and glucose deprivation/reperfusion (OGD/R) through regulating mitochondrial fission and fusion. The process of myocardial ischemia-reperfusion injury was simulated by establishing OGD/R model. The cell proliferation and cytotoxicity detection kit (cell counting kit-8, CCK-8) was used to detect cell viability; the kit method was used to detect intracellular reactive oxygen species (ROS), total glutathione (t-GSH), nitric oxide (NO) content, protein expression levels of mitochondrial fission and fusion, apoptosis-related detection by Western blot. Mitochondrial permeability transition pore (MPTP) detection kit and Hoechst 33342 fluorescence was used to observe the opening level of MPTP, and molecular docking technology was used to determine the molecular target of Sal B. The results showed that relative to control group, OGD/R injury reduced cell viability, increased the content of ROS, decreased the content of t-GSH and NO. Furthermore, OGD/R injury increased the protein expression levels of dynamin-related protein 1 (Drp1), mitofusions 2 (Mfn2), Bcl-2 associated X protein (Bax) and cysteinyl aspartate specific proteinase 3 (caspase 3), and decreased the protein expression levels of Mfn1, increased MPTP opening level. Compared with the OGD/R group, it was observed that Sal B had a protective effect at concentrations ranging from 6.25 to 100 μmol·L-1. Sal B decreased the content of ROS, increased the content of t-GSH and NO, and Western blot showed that Sal B decreased the protein expression levels of Drp1, Mfn2, Bax and caspase 3, increased the protein expression level of Mfn1, and decreased the opening level of MPTP. In summary, Sal B may inhibit the opening of MPTP, reduce cell apoptosis and reduce OGD/R damage in H9C2 cells by regulating the balance of oxidation and anti-oxidation, mitochondrial fission and fusion, thereby providing a scientific basis for the use of Sal B in the treatment of myocardial ischemia reperfusion injury.

18.
Acta Pharmaceutica Sinica ; (12): 336-349, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1016648

ABSTRACT

Small-molecule phenolic substances widely exist in animals and plants, and have some shared biological activities. The metabolism of phenylalanine and tyrosine in the human body, and especially the metabolism of catecholamine neurotransmitters, produces endogenous small-molecule phenols. Endogenous small-molecule phenolic substances are functionally related to the important physiological processes and the occurrence of mental diseases in humans and some animals, which are systematically sorts and summarized in this review. Integrating the previous experimental research and literature analysis on natural small-molecule phenols by our research group, the understanding of the hypothesis that "small-molecule phenol are pharmacological signal carriers" was deepened. Based on above, the concept of "phenolomics" was further proposed, analyzed the research direction and research content which can bring into the knowledge framework of phenolomics. The induction of phenolomics will provide wider perspectives on explaining the pharmacological mechanism of drugs, discovering new drug targets, and finding biomarkers of mental diseases.

19.
China Pharmacy ; (12): 707-711, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1013106

ABSTRACT

OBJECTIVE To investigate the ameliorative effects and mechanism of Sanwei ganlu on hepatic fibrosis in rats. METHODS The rats were randomly divided into normal group, model group, silibinin group (positive control, 50 mg/kg), and Sanwei ganlu low-dose, medium-dose, and high-dose groups (80, 250, 800 mg/kg). Except for normal group, hepatic fibrosis rat models were established by intraperitoneal injection of CCl4 in the other groups of rats. Starting from the 6th week of modeling administration, they were given normal saline or corresponding drugs intragastrically at the same time. At the end of the ninth-week experiment, liver and spleen indexes of rats were calculated; the pathological structure and fibrosis changes of liver tissue were observed by HE, Masson and Sirus Red staining. The contents of alanine transaminase (ALT), aspartate transaminase (AST), procollagen type Ⅲ (PC Ⅲ), collagen type Ⅳ (COL-Ⅳ), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and IL-1β in serum, and hyaluronic acid (HA) and laminin (LN) in liver tissue were all detected. RESULTS Compared with the model group, the liver injury and collagen fiber deposition of rats were improved to different extents in Sanwei ganlu groups and silibinin group; the contents of ALT, AST, PC Ⅲ, COL-Ⅳ, IL-6, TNF-α and IL-1β in serum as well as the contents of HA and LN in liver tissue significantly decreased (P<0.05 or P<0.01). CONCLUSIONS Sanwei ganlu can alleviate the progression of hepatic fibrosis in rats, possibly by inhibiting the synthesis of collagen fiber, reducing transaminase content, down-regulating the levels of HA, LN, PC Ⅲ and COL-Ⅳ, and reducing the inflammatory response.

20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(6): 1787-1790, 2023 Dec.
Article in Chinese | MEDLINE | ID: mdl-38071061

ABSTRACT

OBJECTIVE: To calculate the pharmacokinetic parameters of recombinant human coagulation factor Ⅷ using myPKFiT in patients with severe hemophilia A, and provide an individualized treatment plan for patients. METHODS: A total of 42 patients with severe hemophilia A who were treated with recombinant human coagulation factor Ⅷ were included from January 2021 to December 2021. myPKFiT was used to calculate the pharmacokinetic parameters of FⅧ, and the individualized treatment plan for hemophilia A patients was formulated. RESULTS: The median age of 42 patients with severe hemophilia A was 31(16-50) years old, the average weight was 54.0±9.9 kg, the half-life of FⅧ was 12.05±1.6 h, the time to more than 1% of the baseline was 62.3±15.3 h, and the 0 bleeding rate after the guidance of myPKFiT was significantly increased from 39% to 49%, the Annual bleeding rate was reduced from 3.6±2.5 to 2.1±2.0, and the Annual joint bleeding rate was reduced from 3.2±2.2 to 1.9±0.9, all of which were statistically different (P<0.05). CONCLUSION: Individualized therapy in patients with severe hemophilia A who were guided by myPKFiT assay of pharmacokinetics parameters can significantly reduce the annual bleeding rate and annual joint bleeding rate of patients.


Subject(s)
Factor VIII , Hemophilia A , Adult , Humans , Middle Aged , Blood Coagulation Factors , Factor VIII/pharmacokinetics , Hemorrhage , Recombinant Proteins/pharmacokinetics , Adolescent , Young Adult
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