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1.
Medicine (Baltimore) ; 101(2): e28469, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35029193

RESUMO

INTRODUCTION: Gastric adenocarcinoma of the fundic gland type (GA-FG) is characterized by a well-differentiated neoplasm. More than 100 cases have been reported, but only a few cases have been described in China. Therefore, its clinicopathological characteristics need to be investigated further. Herein, we report five cases and briefly review the relevant literature. PATIENT CONCERNS: Five patients, including three women and two men, were identified in the Ningbo Clinical Pathological Diagnosis Center between March 2017 and July 2020. Patients (case 1, case 2, and case 5) underwent gastroscopy due to epigastric pain. Apart from the lesion, others were occasionally discovered on physical examination. DIAGNOSIS: Gastric adenocarcinoma of the fundic gland type (GA-FG). INTERVENTION: Five patients were treated with endoscopic submucosal dissection. OUTCOMES: Surgical outcomes were good. Esophagogastroduodenoscopy showed a scar with no recurrence, and no postoperative symptoms were observed from 3 to 43 months during the follow-up. CONCLUSION: We present five cases of well-differentiated tubular adenocarcinoma that mimicked the fundic glands. Cell differentiation by MUC2, MUC5AC, MUC6, pepsinogen-I, and H+/K+-ATPase. Immunohistochemical findings in GA-FG suggested differentiation of the fundic glands. In addition, it has a low proliferation. p53 and Her-2 were negative, and ß-catenin was positive in the cytoplasm, indicating that the pathogenesis of this tumor was different from that of traditional intestinal and diffuse gastric carcinomas. In summary, this neoplasm is rare and unusual. To better understand this issue, similar cases should be monitored in the future.

2.
Food Chem ; 366: 130593, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34314928

RESUMO

It is a common belief in China that aging could improve the quality of white tea. However, the stored-induced compositional changes remain elusive. In this study, ten subsets of white tea samples, which had been stored for 1-, 2-, 3-, 4-, 5-, 6-, 7-, 10-, 11- and 13- years, were selected. Macro-compositions were quantified firstly. As the results showed, it was interesting to find total flavonoids, thearubigins (TRs), and theabrownines (TBs) increasing, accompanied with a gradual decrease of total polyphenols, which suggest a conversion of phenolic component in the aging process. Then, nontargeted metabolomics was further conducted on selected subsets of samples, including 1-, 7- and 13- years stored to profile their conversion. As a result, most different metabolites were related to flavonol glycosides and flavone glycosides, suggesting dynamic phenolic component changes were vital in aging. The partial least-squares-discriminant analysis (PLS-DA) also identified them as markers in distinguishing.


Assuntos
Metabolômica , Chá , Flavonoides/análise , Polifenóis/análise
3.
World J Surg Oncol ; 19(1): 336, 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34856986

RESUMO

BACKGROUND: Perianal Paget's disease (PPD) is a rare malignancy, often associated with an underlying adenocarcinoma and a poor prognosis. CASE PRESENTATION: A 69-year-old female was presented with a history of perianal pruritus for 6 months and enlarged inguinal lymph nodes in the left side. Paget cells were confirmed by pathology after a wide excision of perianal skin. Radiotherapy was performed covering the bilateral inguinal lymphatic drainage area. Hepatic metastasis was found 8 months after surgery. Hepatic artery embolization (HAE) and high-intensity focused ultrasound therapy (HIFU) were performed successively. However, hepatic metastasis happened again 3 months later. Ultrasound-guided percutaneous radiofrequency ablation (PRFA) was carried out and various means of inspection could not identify the primary tumor. In the case of rapid progression of the tumor, we gave the patient chemotherapy regimens of XELOX. After 4 cycles of chemotherapy, the tumor marker went down continuously and the hepatic metastasis stayed stable. CONCLUSIONS: Hepatic metastasis from perianal Paget's disease without identified underlying carcinoma may benefit from XELOX on the basis of adenocarcinoma.

4.
Int J Mol Sci ; 22(24)2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34948098

RESUMO

Space radiation presents a substantial threat to travel beyond Earth. Relatively low doses of high-energy particle radiation cause physiological and behavioral impairments in rodents and may pose risks to human spaceflight. There is evidence that 56Fe irradiation, a significant component of space radiation, may be more harmful to males than to females and worsen Alzheimer's disease pathology in genetically vulnerable models. Yet, research on the long-term, sex- and genotype-specific effects of 56Fe irradiation is lacking. Here, we irradiated 4-month-old male and female, wild-type and Alzheimer's-like APP/PS1 mice with 0, 0.10, or 0.50 Gy of 56Fe ions (1GeV/u). Mice underwent microPET scans before and 7.5 months after irradiation, a battery of behavioral tests at 11 months of age and were sacrificed for pathological and biochemical analyses at 12 months of age. 56Fe irradiation worsened amyloid-beta (Aß) pathology, gliosis, neuroinflammation and spatial memory, but improved motor coordination, in male transgenic mice and worsened fear memory in wild-type males. Although sham-irradiated female APP/PS1 mice had more cerebral Aß and gliosis than sham-irradiated male transgenics, female mice of both genotypes were relatively spared from radiation effects 8 months later. These results provide evidence for sex-specific, long-term CNS effects of space radiation.


Assuntos
Doença de Alzheimer , Comportamento Animal/efeitos da radiação , Raios gama , Genótipo , Radioisótopos de Ferro , Presenilina-1 , Caracteres Sexuais , Memória Espacial/efeitos da radiação , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Feminino , Masculino , Camundongos , Camundongos Transgênicos , Presenilina-1/genética , Presenilina-1/metabolismo , Fatores de Tempo
5.
Curr Opin Solid State Mater Sci ; 25(6): 100964, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34729031

RESUMO

Coronavirus disease 2019 (COVID-19), caused by the highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become the worst pandemic disease of the current millennium. To address this crisis, therapeutic nanoparticles, including inorganic nanoparticles, lipid nanoparticles, polymeric nanoparticles, virus-like nanoparticles, and cell membrane-coated nanoparticles, have all offered compelling antiviral strategies. This article reviews these strategies in three categories: (1) nanoparticle-enabled detection of SARS-CoV-2, (2) nanoparticle-based treatment for COVID-19, and (3) nanoparticle vaccines against SARS-CoV-2. We discuss how nanoparticles are tailor-made to biointerface with the host and the virus in each category. For each nanoparticle design, we highlight its structure-function relationship that enables effective antiviral activity. Overall, nanoparticles bring numerous new opportunities to improve our response to the current COVID-19 pandemic and enhance our preparedness for future viral outbreaks.

6.
Adv Mater ; : e2107719, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34783078

RESUMO

Biological neutralization represents a general strategy that deploys therapeutic agents to bind with harmful molecules or infectious pathogens, block their bioactivity, and thus prevent them from causing the diseases. This article provides a comprehensive review of using cell membrane-coated nanoparticles, namely 'cellular nanosponges', as host decoys for a wide range of biological neutralization applications. Compared to traditional neutralization strategies, the cellular nanosponges stand out by mimicking susceptible host cells rather than accommodating the structures of the causative agents for the design of therapeutics. As all pathological agents must interact with host cells for bioactivity, nanosponges bypass the diversity of these agents and create function-driven and broad-spectrum neutralization solutions. The review focuses on the recent progress of using this new nanomedicine platform for neutralization against five primary pathological agents, including bacterial toxins, chemical toxicants, inflammatory cytokines, pathological antibodies, and viruses. Existing studies have established cellular nanosponges as versatile tools for biological neutralization. A thorough review of the cellular nanosponge technology is expected to inspire more refined cellular nanosponge designs and unique neutralization applications to address unsolved medical problems. This article is protected by copyright. All rights reserved.

8.
Front Pharmacol ; 12: 762756, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34712143

RESUMO

Tongluo Yishen (TLYS) decoction is an herb that is extensively applied for the treatment of chronic kidney disease (CKD) in traditional Chinese medicine. In this study, 37 different dominant chemical constituents of TLYS were identified. Rats with unilateral ureteral obstruction (UUO) were used as animal models, and TLYS decoction was administered orally for 14 days. TLYS decoction reduced the levels of renal function indicators, serum creatinine levels and blood urea nitrogen levels and alleviated renal pathological changes. Gene Ontology (GO) and KEGG pathway analyses of RNA sequencing data showed that TLYS decoction had significant effects on biological processes, cellular components and molecular functions in UUO rats and that the phagosome (a membrane source in the early stages of autophagy), lysosome (an important component of autolysosome), and oxidation pathways (which contribute to mitochondrial function) might be related to the antifibrotic effects of TLYS decoction. Moreover, we found significant mitochondrial function impairment, including a decreased mitochondrial membrane potential (MMP) and an imbalance in mitochondrial dynamics, excessive oxidative stress, and activation of Pink1/Parkin-mediated mitophagy in UUO rats. Treatment with TLYS decoction significantly increased the MMP, normalized mitochondrial dynamics and ameliorated renal injury. Moreover, TLYS alleviated the mitophagy clearance deficiency. In conclusion, our study showed that TLYS decoction can ameliorate mitochondrial dynamics by reducing oxidative stress and regulating mitophagy, thereby relieving renal injury, protecting renal function, and reducing renal fibrosis. This study provides support for the application of and further research on TLYS decoction.

9.
Open Med (Wars) ; 16(1): 1378-1385, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34595351

RESUMO

Aim: Renal fibrosis (RF) is a common clinical condition leading to irreversible renal function loss. Tyrosine kinase proteins and microRNAs (miRs) are associated with pathogenesis and we aim to investigate the role of Fer and its partner miR(s) in RF. Method: In silico reproduction of Mouse Kidney FibrOmics browser was performed to identify potential miR(s) and target gene(s). In vivo validation was performed in C57BL/6 mice with unilateral ureteral obstruction (UUO). In vitro validation was performed in rat kidney fibroblast NRK-49F cells. Mimics and inhibitors of miR-29c-3p were constructed. The target gene Fer was monitored by RT-PCR and western blotting. The levels of interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α in serum and media were measured by ELISA. Results: The Fer expression and protein level were gradually increased during 14 days of UUO modeling. miR-29c-3p expression was strongly correlated with that of Fer. In vivo validation showed increased expressions of fibrosis-associated genes and increased phospoho-Smad3 level in the UUO model. Fer-knockdown (KD) significantly decreased expressions of fibrosis-associated genes. Pharmaceutical inhibition of Fer showed similar effects to miR-29c-3p, and miR inhibition showed a significant decrease of excretion of inflammatory factors. Conclusion: Dysregulation of miR-29c-3p and Fer plays a role in RF. Pharmaceutical or genetic inhibition of Fer may serve as the potential treatment for RF.

10.
Am J Cancer Res ; 11(9): 4259-4276, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659886

RESUMO

BACKGROUND: Sintilimab is a humanized monoclonal antibody against the programmed cell death 1 (PD-L1). We aimed to assess the safety and activity of sintilimab monotherapy or in combination with chemotherapy in advanced solid tumors. METHODS: This phase Ib study included six cohorts. Cohort A-C were sintilimab monotherapy settings, and enrolled pretreated patients (2/3 L cohorts). Cohort D-F were treatment-naïve patients (1 L cohorts), and received sintilimab plus different chemotherapies. The primary endpoints were safety and objective response rate (ORR). Exploratory endpoints were potential biomarkers for the prognosis after treatment, such as tumor mutation burden scores (TMB), PD-L1 and lymphocyte-to-monocyte ratio (LMR). RESULTS: The ORR was 14.6% in the 2/3 L cohorts (n=146), and 73.2% in the 1 L cohorts (n=61). The incidence of grade 3-4 adverse events occurred in 55 patients (37.7%) in 2/3 L cohorts, and in 38 (62.3%) in 1 L cohorts. 157 patients had available TMB scores, and in 2/3 L cohorts, patients in the high TMB groups (TMB≥10) showed a longer progression-free survival (PFS) and overall survival (OS) than those in the low TMB groups (TMB<10). No significant differences in PFS and OS were observed across different PD-L1 groups in both 1 L and 2/3 L cohorts. A high LMR was significantly associated with an improved PFS in 1 L cohorts (P=0.022). CONCLUSION: Sintilimab alone or combined with chemotherapy had a tolerable safety profile in solid tumors. The combination therapy showed a favorable activity with advanced non-small cell lung cancer and gastric or esophagogastric junction adenocarcinoma. LMR might be a prognostic factor for the combination regimen in these patients. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT02937116. Registered 18 October 2016.

11.
Adv Healthc Mater ; : e2101349, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34468090

RESUMO

White blood cells (WBCs) are immune cells that play essential roles in critical diseases including cancers, infections, and inflammatory disorders. Their dynamic and diverse functions have inspired the development of WBC membrane-coated nanoparticles (denoted "WBC-NPs"), which are formed by fusing the plasma membranes of WBCs, such as macrophages, neutrophils, T cells, and natural killer cells, onto synthetic nanoparticle cores. Inheriting the entire source cell antigens, WBC-NPs act as source cell decoys and simulate their broad biointerfacing properties with intriguing therapeutic potentials. Herein, the recent development and medical applications of WBC-NPs focusing on four areas, including WBC-NPs as carriers for drug delivery, as countermeasures for biological neutralization, as nanovaccines for immune modulation, and as tools for the isolation of circulating tumor cells and fundamental research is reviewed. Overall, the recent development and studies of WBC-NPs have established the platform as versatile nanotherapeutics and tools with broad medical application potentials.

12.
Cell Transplant ; 30: 9636897211041585, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34470528

RESUMO

Global cerebral ischemia induced by cardiac arrest usually leads to poor neurological outcomes. Numerous studies have focused on ways to prevent ischemic damage in the brain, however clinical therapies are still limited. Our previous studies revealed that delta opioid receptor (DOR) activation with [d-Ala2, d-Leu5] enkephalin (DADLE), a DOR agonist, not only significantly promotes neuronal survival on day 3, but also improves spatial memory deficits on days 5-9 after ischemia. However, the neurological mechanism underlying DADLE-induced cognitive recovery remains unclear. This study first examined the changes in neuronal survival in the CA1 region at the advanced time point (day 7) after ischemia/reperfusion (I/R) injury and found a significant amelioration of damaged CA1 neurons in the rats treated with DADLE (2.5 nmol) when administered at the onset of reperfusion. The structure and function of CA1 neurons on days 3 and 7 post-ischemia showed significant improvements in both the density of the injured dendritic spines and the basic transmission of the impaired CA3-CA1 synapses following DADLE treatment. The molecular changes involved in DADLE-mediated synaptic modulation on days 3 and 7 post-ischemia implied the time-related differential regulation of PKCα-MARCKS on the dendritic spine structure and of BDNF- ERK1/2-synapsin I on synaptic function, in response to ischemic/reperfusion injury as well as to DADLE treatment. Importantly, all the beneficial effects of DADLE on ischemia-induced cellular, synaptic, and molecular deficits were eliminated by the DOR inhibitor naltrindole (2.5 nmol). Taken together, this study suggested that DOR activation-induced protective signaling pathways of PKCα-MARCKS involved in the synaptic morphology and BDNF-ERK-synapsin I in synaptic transmission may be engaged in the cognitive recovery in rats suffering from advanced cerebral ischemia.

14.
J Thorac Oncol ; 16(12): 2109-2120, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34358724

RESUMO

INTRODUCTION: Sintilimab plus chemotherapy significantly prolonged progression-free survival (PFS) compared with chemotherapy alone in nonsquamous NSCLC in the ORIENT-11 study. Updated overall survival (OS) and PFS data and corresponding biomarker analyses are reported here. METHODS: In this study, a total of 397 patients with previously untreated, locally advanced or metastatic nonsquamous NSCLC were assigned to sintilimab plus chemotherapy combination treatment (combo) group or placebo plus chemotherapy treatment group. The patients were stratified by programmed death-ligand 1 (PD-L1) expression levels. Immune signature profiles from tumor RNA sequencing and PD-L1 immunohistochemistry were correlated with clinical outcome to identify predictive biomarkers. RESULTS: As of January 2021, with median follow-up of 22.9 months, median OS was significantly improved in the combo group compared with the placebo plus chemotherapy treatment group (not reached versus 16.8 mo; hazard ratio [HR] = 0.60, 95% confidence interval [CI]: 0.45-0.79, p = 0.0003). High or medium immune cell infiltration was strongly associated with improved PFS in the combo group, in contrast to absent or low immune cell infiltration, which suggests that chemotherapy could not prime "immune deserts" to obtain benefit from programmed cell death protein-1 inhibition. In particular, high major histocompatibility complex (MHC) class II presentation pathway expression was significantly correlated with prolonged PFS (HR = 0.32, 95% CI: 0.19-0.54, p < 0.0001) and OS (HR = 0.36, 95% CI: 0.20-0.64, p = 0.0005) in the combo group. Importantly, patients with low or absent PD-L1 but high MHC class II expression could still benefit from the combo treatment. In contrast, MHC class I antigen presentation pathway was less relevant in this combination setting. CONCLUSIONS: The addition of sintilimab to chemotherapy resulted to significantly longer OS in nonsquamous NSCLC. Expression of MHC class II antigen presentation pathway could identify patients benefiting most from this combination.

15.
Bioengineered ; 12(1): 4768-4779, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34348577

RESUMO

Nitrous Oxide (N2O) has been shown to be neurotoxic, but its specific mechanism is still unclear. The purpose of this work is to probe into the impact of N2O on nerve cell injury through regulating thioredoxin-interacting protein (TXNIP)/the NOD-like receptor domain of pyrin containing 3 (NLRP3) pathway. The results indicated that, N2O exposure elevated TXNIP/NLRP3 expression in vivo and in vitro, led to declined learning and memory capabilities in mice, reduced apoptosis rate in hippocampal neuron and Nissl bodies, elevated inflammatory factors TNF-α, IL-1ß and IL-6 levels, as well as cleaved caspase-3 and Bax expressions, and reduced Bcl-2 expression. Overexpressing TXNIP or NLRP3 further aggravated these injuries, but knocking down TXNIP or NLRP3 improved them. CO-IP indicated that TXNIP and NLRP3 can be combined, with interaction relationship. All in all, the results manifested that N2O is available to promote nerve cell inflammation and apoptosis through activating the TXNIP/NLRP3 pathway that can be used as a potential target for N2O-induced nerve damage in the future.

16.
Drug Des Devel Ther ; 15: 2059-2089, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34040346

RESUMO

Purpose: One of the most common types of male infertility is recognized as oligoasthenozoospermia (OA), characterized by low sperm count and quality in males. As a traditional Chinese medicine (TCM), Cuscutae Semen-Mori Fructus coupled-herbs (CSMFCH) has been known to act a curative effect on OA for thousands of years. Nevertheless, the substantial basis and molecular mechanism of CSMFCH in treating OA remain elusive. Methods: Herein, an integrated approach, including network pharmacology, molecular docking, and experiment validation, was utilized to reveal the new candidate active component and mechanism of CSMFCH in treating OA. Results: The results show that kaempferol is the most significant bioactive component of CSMFCH on OA. The mechanism and targets of CSMFCH against OA are relevant to hormone regulation, oxidant stress, and reproductive promotion. In order to validate network pharmacology results, molecular docking and experiment validation were conducted. In detail, molecular docking was employed to verify the strong binding interactions between kaempferol and the core targets. UHPLC-Q-Orbitrap-MS was used to identify kaempferol in the CSMFCH extract. In vitro and in vivo experiments further proved CSMFCH and kaempferol could enhance the mouse Leydig (TM3) and mouse Sertoli (TM4) cell viability, improve the male reproductive organ weights, sperm quality, and decrease testis tissue damage in the OA mouse model induced by CP. Conclusion: Our results not only identify the new candidate active component of CSMFCH in treating OA but also provide new insights into the mechanisms of CSMFCH against OA.


Assuntos
Astenozoospermia/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Simulação de Acoplamento Molecular , Extratos Vegetais/uso terapêutico , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Frutas/química , Masculino , Espectrometria de Massas , Medicina Tradicional Chinesa , Camundongos , Camundongos Endogâmicos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação
17.
Adv Ther (Weinh) ; 4(4)2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33997269

RESUMO

Glioblastoma multiforme (GBM) is the most common and deadliest form of brain tumor and remains amongst the most difficult cancers to treat. Brevican (Bcan), a central nervous system (CNS)-specific extracellular matrix protein, is upregulated in high-grade glioma cells, including GBM. A Bcan isoform lacking most glycosylation, dg-Bcan, is found only in GBM tissues. Here, dg-Bcan is explored as a molecular target for GBM. In this study, we screened a d-peptide library to identify a small 8-amino acid dg-Bcan-Targeting Peptide (BTP) candidate, called BTP-7 that binds dg-Bcan with high affinity and specificity. BTP-7 is preferentially internalized by dg-Bcan-expressing patient-derived GBM cells. To demonstrate GBM targeting, we radiolabeled BTP-7 with 18F, a radioisotope of fluorine, and found increased radiotracer accumulation in intracranial GBM established in mice using positron emission tomography (PET) imaging. dg-Bcan is an attractive molecular target for GBM, and BTP-7 represents a promising lead candidate for further development into novel imaging agents and targeted therapeutics.

18.
J Thorac Oncol ; 16(9): 1501-1511, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34048947

RESUMO

INTRODUCTION: The standard chemotherapy for squamous NSCLC (sqNSCLC) includes platinum plus gemcitabine. Sintilimab, an anti-programmed cell death protein 1 antibody, plus platinum and gemcitabine (GP) has revealed encouraging efficacy as first-line therapy for sqNSCLC in a phase 1b study. We conducted a randomized, double-blind, phase 3 study to further compare the efficacy and safety of sintilimab with placebo, both in combination with GP. METHODS: ORIENT-12, a randomized, double-blind, phase 3 study, was conducted at 42 centers in the People's Republic of China (ClinicalTrials.gov, number NCT03629925). Patients with locally advanced or metastatic sqNSCLC and without EGFR-sensitive mutations or ALK rearrangements were enrolled in the study. The stratification factors included clinical stage, choice of platinum, and programmed death-ligand 1 tumor proportion score. The patients, investigators, research staff, and sponsor team were masked to treatment assignment. Eligible patients were randomized 1:1, using an integrated web-response system, to receive sintilimab 200 mg or placebo plus GP every 3 weeks for four or six cycles, followed by sintilimab or placebo as maintenance therapy until disease progression or 2 years. The primary end point was progression-free survival (PFS), assessed by an independent radiographic review committee. RESULTS: Between September 25, 2018 and July 26, 2019, a total of 543 patients were screened, of whom 357 patients were randomized to the sintilimab-GP group (n = 179) and the placebo-GP group (n = 178). After a median follow-up period of 12.9 months, sintilimab-GP continued to reveal a meaningful improvement in PFS than placebo-GP (hazard ratio = 0.536 [95% confidence interval: 0.422-0.681], p < 0.00001). Treatment-emergent adverse events of grade 3 or worse occurred in 86.6% patients in the sintilimab-GP group and in 83.1% in the placebo-GP group. The incidence of treatment-emergent adverse event leading to death was 4.5% and 6.7% in the two treatment groups, respectively. CONCLUSIONS: Regarding PFS, sintilimab plus GP reveals clinical benefit than GP alone as first-line therapy in patients with locally advanced or metastatic sqNSCLC. The toxicity was acceptable, and no new unexpected safety signals were observed.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Pulmonares , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Desoxicitidina/análogos & derivados , Método Duplo-Cego , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Platina/uso terapêutico
19.
Anim Reprod ; 17(4): e20200521, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33791027

RESUMO

Septin14 is an important spermatogenesis related gene involved in the pathogenesis of male infertility that has not been well studied. Here, full-length Septin14 cDNA of the Banna mini-pig inbred line (BMI) was cloned using the RACE method and expressed in pig kidney epithelial cells (PK15) and E. coli Rosetta (DE3) cells. Septin14 expression was identified in somatic tissues and testis in different developmental stages. The pig Septin14 CDS is 1,299 bp long, and encodes a peptide (or protein) of 432 amino acids (MW=50.4 kDa). Phylogenetic analysis indicated that pig Septin14 was highly evolutionarily conserved. Subcellular localization of GFP-tagged Septin14 fusion protein revealed that Septin14 was distributed throughout the testicular cells. Among 34 pig tissues, Septin14 mRNA was found specifically in testis and seminal vesicle. In six different postnatal developmental stages, the testicular level of Septin14 mRNA was barely detectable on day 2, while the highest level occurred on day 75. The spatiotemporal expression profile of Septin14, reported herein for the first time in pig, indicated that Septin14 might be involved in the division, development and apoptosis of germ cells. Furthermore, using a pET prokaryotic expression system, we expressed and isolated recombinant 67.9 kDa Septin14 protein.

20.
Gen Physiol Biophys ; 40(2): 147-154, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33881001

RESUMO

Renal fibrosis poses critical health problem. We aimed to investigate role of let-7i-5p in renal fibrosis. In silico reproduction of Mouse Kidney FibrOmics browser was used to identify potential target of let-7i-5p. In vivo validation was conducted in C57BL/6 mice with unilateral ureteral obstruction (UUO) and folic acid (FA) induction. In vitro validation was performed in transforming growth factor (TGF)-ß1-treated HK-2 cells. Mimics and inhibitors of let-7i-5p, and target gene polypeptide N-acetylgalactosaminyltransferase 1 (GALNT1) were monitored by RT-PCR and Western blotting. Fibrosis markers, injury markers, and house-keeping genes were evaluated. Levels of interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α in serum and media were measured by ELISA. In silico analysis showed gradual increase of let-7i-5p and decrease of GALNT1 over time and the combination was validated both in mouse and human miR-gene target prediction databases. Expression of GALNT1 decreased while expression of let-7i-5p increased in renal tissues of both UUO and FA mice. Serum IL-6, IL-1ß, and TNF-α levels were elevated in vivo. In vitro models revealed negative correlation between expression levels of let-7i-5p and GALNT1. Overexpression of let-7i-5p inhibited GALNT1 expression and reduced release of inflammatory factors. In conclusion, overexpression of GALNT1 may combat the inflammation induced by let-7i-5p.


Assuntos
Nefropatias , MicroRNAs , Animais , Fibrose , Rim/patologia , Nefropatias/genética , Nefropatias/patologia , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética
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