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1.
Polymers (Basel) ; 16(1)2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38201822

RESUMO

In the pursuit of advancing materials for methane storage, a critical consideration arises given the prominence of natural gas (NG) as a clean transportation fuel, which holds substantial potential for alleviating the strain on both energy resources and the environment in the forthcoming decade. In this context, a novel approach is undertaken, employing the rigid triptycene as a foundational building block. This strategy is coupled with the incorporation of dichloromethane and 1,3-dichloropropane, serving as rigid and flexible linkers, respectively. This combination not only enables cost-effective fabrication but also expedites the creation of two distinct triptycene-based hypercrosslinked polymers (HCPs), identified as PTN-70 and PTN-71. Surprisingly, despite PTN-71 manifesting an inferior Brunauer-Emmett-Teller (BET) surface area when compared to the rigidly linked PTN-70, it showcases remarkably enhanced methane adsorption capabilities, particularly under high-pressure conditions. At a temperature of 275 K and a pressure of 95 bars, PTN-71 demonstrates an impressive methane adsorption capacity of 329 cm3 g-1. This exceptional performance is attributed to the unique flexible network structure of PTN-71, which exhibits a pronounced swelling response when subjected to elevated pressure conditions, thus elucidating its superior methane adsorption characteristics. The development of these advanced materials not only signifies a significant stride in the realm of methane storage but also underscores the importance of tailoring the structural attributes of hypercrosslinked polymers for optimized gas adsorption performance.

2.
J Nat Prod ; 87(1): 141-151, 2024 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-38128907

RESUMO

Twelve new austalide meroterpenoids (1-12) were isolated from the endophytic fungus Diaporthe sp. XC1211. Their structures were elucidated by extensive spectroscopic analysis. The absolute configurations of compounds 1, 3, 4, and 6 were established by single-crystal X-ray diffraction, whereas those for the others were established by experimental electronic circular dichroism (ECD) data analysis. Compounds 1-12 represent a rare class of austalides with a 24α-CH3. Compounds 2 and 5 demonstrated potent proliferation inhibitory effects against LPS-induced B cells with IC50 values of 6.7 (SI = 3.6) and 3.8 (SI > 13) µM, respectively. Compounds 2 and 5 decreased the secretion of IL-6 in LPS-induced B cells in a dose-dependent manner.


Assuntos
Fungos , Lipopolissacarídeos , Estrutura Molecular , Lipopolissacarídeos/farmacologia , Cristalografia por Raios X , Dicroísmo Circular
3.
Front Cell Neurosci ; 17: 1257347, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38026694

RESUMO

The Drosophila larval neuromuscular junction (NMJ) is a well-known model system and is often used to study synapse development. Here, we show synaptic degeneration at NMJ boutons, primarily based on transmission electron microscopy (TEM) studies. When degeneration starts, the subsynaptic reticulum (SSR) swells, retracts and folds inward, and the residual SSR then degenerates into a disordered, thin or linear membrane. The axon terminal begins to degenerate from the central region, and the T-bar detaches from the presynaptic membrane with clustered synaptic vesicles to accelerate large-scale degeneration. There are two degeneration modes for clear synaptic vesicles. In the first mode, synaptic vesicles without actin filaments degenerate on the membrane with ultrafine spots and collapse and disperse to form an irregular profile with dark ultrafine particles. In the second mode, clear synaptic vesicles with actin filaments degenerate into dense synaptic vesicles, form irregular dark clumps without a membrane, and collapse and disperse to form an irregular profile with dark ultrafine particles. Last, all residual membranes in NMJ boutons degenerate into a linear shape, and all the residual elements in axon terminals degenerate and eventually form a cluster of dark ultrafine particles. Swelling and retraction of the SSR occurs prior to degradation of the axon terminal, which degenerates faster and with more intensity than the SSR. NMJ bouton degeneration occurs under normal physiological conditions but is accelerated in Drosophila neurexin (dnrx) dnrx273, Drosophila neuroligin (dnlg) dnlg1 and dnlg4 mutants and dnrx83;dnlg3 and dnlg2;dnlg3 double mutants, which suggests that both neurexin and neuroligins play a vital role in preventing synaptic degeneration.

4.
BMC Cancer ; 23(1): 854, 2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37697271

RESUMO

BACKGROUND: Dysbiosis of gut microbiota has been linked to numerous diseases, including cancer. The unique role of gut microbiota in urological tumors is gaining prominence. However, it is still controversial whether the dysbiosis of gut microbiota should be one of the etiological factors of bladder cancer (BCa), prostate cancer (PCa) or kidney cancer (KCa). MATERIALS AND METHODS: The microbiome genome-wide association study (GWAS) from the MiBioGen consortium (18,340 samples of 24 population-based cohorts) was utilized as the exposure data. Additionally, outcomes data (951 BCa cases and 307,092 controls; 1,631 KCa cases and 238,678 controls; 79,148 PCa cases and 61,106 controls) were extracted from the GWAS of the FinnGen and PRACTICAL consortia. To detect the potential causative bacterial traits for BCa, PCa, and KCa, a two-sample Mendelian randomization (MR) analysis was performed, employing the inverse-variance weighted or Wald ratio method. Sensitivity analyses were subsequently conducted to explore the robustness of the primary results. Finally, the reverse MR analysis was undertaken to mitigate the reverse causation. RESULTS: This study suggested that Bifidobacterium (p = 0.030), Actinobacteria (p = 0.037 for phylum, 0.041 for class), and Ruminococcustorques group (p = 0.018), exhibited an association with an increased risk of BCa using either the inverse-variance weighted or Wald ratio method. By utilizing the Wald ratio method, Allisonella (p = 0.004, p = 0.038) was associated with a decreased risk of BCa and PCa, respectively. Furthermore, Ruminococcustorques group (p = 0.028) and Erysipelatoclostridium (p = 0.048) were causally linked to an elevated risk of KCa. CONCLUSIONS: This MR study supports that genetically predicted gut microbiota is causally related to BCa, PCa and KCa. Additionally, distinct bacterial traits are identified in relation to each tumor type.


Assuntos
Carcinoma de Células Renais , Microbioma Gastrointestinal , Neoplasias Renais , Neoplasias Urológicas , Masculino , Humanos , Microbioma Gastrointestinal/genética , Disbiose , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana
5.
Front Immunol ; 14: 1077003, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37033917

RESUMO

Background: Osteoarthritis (OA) is a prevalent senescence-related disease with substantial joint pain, loss of joint function, and cartilage degeneration. Because of the paucity of single-cell studies of OA and the gene dropout problem of single-cell RNA sequencing, it is difficult to acquire an in-depth understanding of the molecular characteristics of various chondrocyte clusters. Methods: Here, we aimed to provide new insights into chondrocyte senescence and a rationale for the development of effective intervention strategies for OA by using published single-cell RNA-sequencing data sets and the metaVIPER algorithm (Virtual Inference of Protein activity by Enriched Regulon). This algorithm was employed to present a proteome catalog of 62,449 chondrocytes from the cartilage of healthy individuals and OA patients at single-cell resolution. Furthermore, histopathologic analysis was carried out in cartilage samples from clinical patients and experimental mouse models of OA to validate above results. Results: We identified 16 protein-activity-based chondrocyte clusters as well as the underlying master regulators in each cluster. By assessing the enrichment score of each cluster in bulk RNA-sequencing data, followed by gene-set variation analysis, we preliminarily identified a novel subpopulation of chondrocytes (cluster 3). This clinically relevant cluster was predicted to be the main chondrocyte cluster responsible for maintaining cellular homeostasis and anti-senescence. Specifically, we uncovered a set of the key leading-edge proteins of cluster 3 by validating the robustness of the above results using another human chondrocyte single-cell RNA-sequencing data set, consisting of 24,675 chondrocytes. Furthermore, cartilage samples from clinical patients and experimental mouse models of OA were used to evaluate the expression patterns of these leading-edge proteins, and the results indicated that NDRG2, TSPYL2, JMJD6 and HMGB2 are closely associated with OA pathogenesis and might play critical roles in modulating cellular homeostasis and anti-senescence in chondrocytes. Conclusion: Our study revealed a novel subpopulation of chondrocytes that are critical for anti-progression of OA and the corresponding master regulator proteins, which might serve as therapeutic targets in OA.


Assuntos
Cartilagem Articular , Osteoartrite , Humanos , Camundongos , Animais , Condrócitos/metabolismo , Cartilagem Articular/metabolismo , Osteoartrite/metabolismo , RNA/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Histona Desmetilases com o Domínio Jumonji/metabolismo
6.
BMC Complement Med Ther ; 23(1): 37, 2023 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-36747185

RESUMO

OBJECTIVE: A multicriteria decision analysis (MCDA) model was used to evaluate the benefits and risks of traditional Chinese medicine preparations of sinomenine alone or in combination with conventional drugs in the treatment of rheumatoid arthritis (RA) and to provide a basis for the rational clinical application of sinomenine. METHODS: A study search was performed using six major databases, and Review Manager 5.3 was used for data analysis. Then, an MCDA model evaluation system was established for the treatment of RA with sinomenine preparations, and the benefit values, risk values, and total benefit-risk values of sinomenine preparations alone or in combination with conventional drugs were calculated using Hiview 3.2 software. Finally, Monte Carlo simulations were performed using Crystal Ball embedded in Excel software to calculate the 95% confidence intervals (95% CI), and the probability of the differences between the 2 drug regimens was determined to optimize the evaluation results. RESULTS: Forty-four randomized controlled trials (RCTs) were included. Quantitative assessment of the MCDA model showed that the sinomenine preparation alone offered less benefits than when combined with conventional drugs with a benefit difference of 20 (95% CI 3.06, 35.71). However, the risk of the combination was significantly lower with a risk difference of 13(95% CI -10.26, 27.52). The total value of the benefit-risk of sinomenine alone and in combination with conventional drugs was 46 and 53 at 60% and 40% of the benefit-risk ratio of the two dosing regimens, respectively, with a difference of 7 (95% CI -4.26, 22.12). The probability that the comprehensive score of the combined regimen is greater than that of sinomenine alone is 90.1%, and the evaluation was steady. CONCLUSION: The benefit-risk of the combined application regimen of sinomenine is greater than that of sinomenine alone.


Assuntos
Artrite Reumatoide , Medicina Tradicional Chinesa , Humanos , Artrite Reumatoide/tratamento farmacológico , Técnicas de Apoio para a Decisão , Medição de Risco
7.
Front Psychol ; 13: 1037786, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36467242

RESUMO

This study examines depressive symptoms faced by non-native international medical students studying in China during the COVID-19 pandemic. The targeted population for this cross-sectional study included non-native medical students studying in Chinese universities. This study used convenience sampling. An online, self-administered questionnaire was distributed to international medical students studying in Chinese universities from February 2020 to June 2021. The questionnaire collected demographic data, information regarding struggles faced, and used the CES-D-10 Likert scale to assess both the challenges and depression symptoms, respectively. By analyzing the 1,207 students' responses, the study found that students with poor Chinese language were two times more likely to suffer from depressive symptoms (OR = 2.67; value of p 0.00). Moreover, female students were found more prone (76.35%) than their male counterparts (44.96%). The study found that food adaptability, health issues, accommodation issues, and financial issues were related factors contributing to depressive symptoms among non-native international medical students during the COVID-19 pandemic. The study tried to highlight the factors that resulted in depressive symptoms among non-native international medical students, and the findings may help diplomatic representatives take necessary actions to help their citizens during this difficult time.

8.
World J Gastrointest Oncol ; 14(9): 1711-1726, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36187388

RESUMO

BACKGROUND: The effects of consolidation chemotherapy (CC) in neoadjuvant therapy in locally advanced rectal cancer (LARC) have been explored. However, the optimal neoadjuvant chemoradiotherapy (NCRT) and surgery interval, regimen, and cycles of chemotherapy remains unclear. AIM: To evaluate the effects of one to two cycles of CC with capecitabine on high-risk patients with LARC without extending NCRT and surgery interval. METHODS: We retrospectively evaluated high-risk patients with LARC, who were defined as having at least one of the following factors by magnetic resonance imaging: depth of invasion beyond the muscularis propria of more than 5 mm (cT3c-cT3d), T4, meso-rectal fascia or extramural vascular invasion positive, and treatment date between January 2015 and July 2019 in our center. Patients were divided into the CC and non-CC group according to whether they received CC (capecitabine 1000 mg/m2 twice daily from days 1 to 14 every 21 d) after NCRT. Propensity score matching (PSM) and inverse probability of treatment weight (IPTW) were used to balance the differences between the two groups. The main outcome was the complete response (CR) rate. RESULTS: A total of 265 patients were enrolled: 136 patients in the CC group and 129 patients in the non-CC group. The median interval was 70 d (range, 37-168). The CR rate was 24.3% and 16.3% (P = 0.107) in the CC and non-CC groups' original samples, respectively. After PSM and IPTW, the CR rate in the CC group was higher than that in non-CC group (27.6% vs 16.2%, P = 0.045; 25.9% vs 16.3%, P = 0.045). The median follow-up was 39.8 mo (range, 2.9-74.8), and there were no differences in 3-year non-regrowth disease-free survival nor overall survival in the original samples (73.2% vs 71.9%, P = 0.913; 92.3% vs 86.7%, P = 0.294), PSM (73.2% vs 73.5%, P = 0.865; 92.5% vs 89.3%, P = 0.612), and IPTW (73.8% vs 72.1%, P = 0.913; 92.4% vs 87.4%, P = 0.294). There was also no difference in grade 2 or higher acute toxicity during neoadjuvant therapy in the two groups (49.3% vs 53.5%, P = 0.492). CONCLUSION: One to two cycles of CC with capecitabine after NCRT was safe and increased the CR rate in high-risk LARC but failed to improve the long-term outcomes.

9.
World J Gastrointest Oncol ; 14(5): 1027-1036, 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35646284

RESUMO

BACKGROUND: Accurate target volume delineation is the premise for the implementation of precise radiotherapy. Inadequate target volume delineation may diminish tumor control or increase toxicity. Although several clinical target volume (CTV) delineation guidelines for rectal cancer have been published in recent years, significant interobserver variation (IOV) in CTV delineation still exists among radiation oncologists. However, proper education may serve as a bridge that connects complex guidelines with clinical practice. AIM: To examine whether an education program could improve the accuracy and consistency of preoperative radiotherapy CTV delineation for rectal cancer. METHODS: The study consisted of a baseline target volume delineation, a 150-min education intervention, and a follow-up evaluation. A 42-year-old man diagnosed with stage IIIC (T3N2bM0) rectal adenocarcinoma was selected for target volume delineation. CTVs obtained before and after the program were compared. Dice similarity coefficient (DSC), inclusiveness index (IncI), conformal index (CI), and relative volume difference [ΔV (%)] were analyzed to quantitatively evaluate the disparities between the participants' delineation and the standard CTV. Maximum volume ratio (MVR) and coefficient of variation (CV) were calculated to assess the IOV. Qualitative analysis included four common controversies in CTV delineation concerning the upper boundary of the target volume, external iliac area, groin area, and ischiorectal fossa. RESULTS: Of the 18 radiation oncologists from 10 provinces in China, 13 completed two sets of CTVs. In quantitative analysis, the average CTV volume decreased from 809.82 cm3 to 705.21 cm3 (P = 0.001) after the education program. Regarding the indices for geometric comparison, the mean DSC, IncI, and CI increased significantly, while ΔV (%) decreased remarkably, indicating improved agreement between participants' delineation and the standard CTV. Moreover, an 11.80% reduction in MVR and 18.19% reduction in CV were noted, demonstrating a smaller IOV in delineation after the education program. Regarding qualitative analysis, the greatest variations in baseline were observed at the external iliac area and ischiorectal fossa; 61.54% (8/13) and 53.85% (7/13) of the participants unnecessarily delineated the external iliac area and the ischiorectal fossa, respectively. However, the education program reduced these variations. CONCLUSION: Wide variations in CTV delineation for rectal cancer are present among radiation oncologists in mainland China. A well-structured education program could improve delineation accuracy and reduce IOVs.

10.
BMC Vet Res ; 17(1): 374, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34872574

RESUMO

BACKGROUND: Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals. As a transboundary animal disease, the prevention and control of FMD are important. This study was based on spatial multi-criteria decision analysis (MCDA) to assess FMD risk areas in mainland China. Ten risk factors were identified for constructing risk maps by scoring, and the analytic hierarchy process (AHP) was used to calculate the criteria weights of all factors. Different risk factors had different units and attributes, and fuzzy membership was used to standardize the risk factors. The weighted linear combination (WLC) and one-at-a-time (OAT) were used to obtain risk and uncertainty maps as well as to perform sensitivity analysis. RESULTS: Four major risk areas were identified in mainland China, including western (parts of Xinjiang and Tibet), southern (parts of Yunnan, Guizhou, Guangxi, Sichuan and Guangdong), northern (parts of Gansu, Ningxia and Inner Mongolia), and eastern (parts of Hebei, Henan, Anhui, Jiangsu and Shandong). Spring is the main season for FMD outbreaks. Risk areas were associated with the distance to previous outbreak points, grazing areas and cattle density. Receiver operating characteristic (ROC) analysis indicated that the risk map had good predictive power (AUC=0.8634). CONCLUSIONS: These results can be used to delineate FMD risk areas in mainland China, and veterinary services can adopt the targeted preventive measures and control strategies.


Assuntos
Doenças dos Bovinos , Febre Aftosa , Animais , Bovinos , Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/prevenção & controle , China/epidemiologia , Técnicas de Apoio para a Decisão , Febre Aftosa/epidemiologia , Febre Aftosa/prevenção & controle
11.
J Nat Prod ; 84(7): 1904-1914, 2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34176266

RESUMO

Twelve new [11]-chaetoglobosins, chaetopseudeurins A-L (1-12), were identified from the fermentation of the endophytic fungus Pseudeurotium bakeri P1-1-1. Their structures with absolute configurations were elucidated by detailed interpretation of NMR spectroscopy, mass spectrometry, and single-crystal X-ray diffraction. Compounds 2 and 5-7 exhibited significant cytotoxicities against seven human cancer cell lines, with IC50 values ranging from 4.7 ± 1.0 to 12.2 ± 0.7 µM, and induced G2/M cell cycle arrest and apoptosis in MCF-7 and A427 cells dose dependently. Western blot analysis showed that compound 2 induced apoptosis of MCF-7 cells via the Bcl-2/caspase-3/PARP pathway.


Assuntos
Apoptose/efeitos dos fármacos , Ascomicetos/química , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Alcaloides Indólicos/farmacologia , Linhagem Celular Tumoral , China , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Alcaloides Indólicos/isolamento & purificação , Células MCF-7 , Estrutura Molecular
12.
Radiother Oncol ; 161: 132-139, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34126137

RESUMO

BACKGROUND AND PURPOSE: Elective irradiation of the external iliac lymph nodes (EIN) has always been advocated for T4b rectal cancer with anterior organ invasion without convincing evidence. This study aimed to explore the patterns of treatment failure for locally advanced T4b rectal cancer treated using neoadjuvant chemoradiotherapy (NCRT) and surgery. This information may help to clarify whether the current definition of the clinical target volume (CTV) is still appropriate. MATERIALS AND METHODS: We retrospectively analyzed data from 126 patients with locally advanced T4b rectal cancer who received NCRT, without elective EIN irradiation, followed by surgery between January 2010 and October 2018. Pretreatment magnetic resonance imaging was used to identify the T4b disease in all cases. The locoregional recurrence (LRR) rate and EIN failure rate were evaluated, and the LRR locations were identified using a three-dimensional model. RESULTS: After a median follow-up of 53.9 months, LRR occurred in 11.1% of patients (14/126). All LRRs were located in the previously irradiated fields and below the S2-S3 junction. The EIN failure rate was 0.8% (1/126) among all patients and 1.8% (1/56) in the group with anterior genitourinary organ invasion. The estimated 4-year distant relapse-free survival, disease-free survival and overall survival were 79.3%, 73.2% and 86.9%, respectively. CONCLUSIONS: It may be feasible to exclude the external iliac region from the CTV during NCRT for locally advanced T4b rectal cancer. However, further studies are needed to clarify whether the cranial border of the CTV can be lowered.


Assuntos
Terapia Neoadjuvante , Neoplasias Retais , Quimiorradioterapia , Humanos , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Estudos Retrospectivos
13.
Ann Transl Med ; 9(3): 217, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33708844

RESUMO

BACKGROUND: Lateral pelvic lymph node (LPLN) is approximately 11-14% and always associated with poorer prognosis. This study investigated the efficacy and safety of simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT) based on neoadjuvant chemoradiotherapy (NCRT) on locally advanced rectal cancer (LARC) patients with clinically suspected positive LPLNs. METHODS: We retrospectively screened distal LARC patients with NCRT in our center from May 2016 and June 2019. The diagnostic criteria of positive LPLN were nodes of over 7 mm in short axis and irregular border or mixed-signal intensity. All patients with clinically suspected positive LPLN received 56-60 Gy SIB-IMRT in the LPLN area. Concurrent chemotherapy regimens were capecitabine as monotherapy treatment or in combination with oxaliplatin. The toxicities, local-regional recurrence (LRR), and disease-free survival (DFS) were investigated. RESULTS: Fifty-two eligible patients with clinically suspected positive LPLN were screened and analyzed. The median distance from the distal tumor to the anal verge was 4 cm (range, 0-8 cm), while magnetic resonance imaging (MRI) analysis revealed the median short diameter of the pelvic LPLN to be 8 mm (range, 7-20 mm). There were 28 (53.8%) mesorectal fascia (MRF) positive and 22 (42.3%) extramural venous invasion (EMVI) positive patients. A radiotherapy dose of 41.8 Gy was administered to the pelvic area, while the LPLN received a median SIB dose of 60.0 Gy (range, 56-60 Gy) across 22 fractions. Synchronous capecitabine with or without oxaliplatin was administered during radiotherapy. In summary, 15 (28.8%) patients displayed grade 2-3 radiation-related toxicity, 8 (15.4%) patients underwent additional LPLN dissection, and positive nodes (26 nodes in total) were not observed. One patient suffered a LLR in the presacral region. The median follow-up duration was 21.2 months (range, 4.7-45.0 months), while the duration of 1- and 2-year DFS were 89.9% and 74.6%, respectively. Patients did not display LPLN recurrence. CONCLUSIONS: The safety and efficacy of SIB-IMRT on clinically suspected positive LPLN of LARC patients were deemed acceptable. Patients did not exhibit in-field LPLN recurrence after NCRT combined with single total mesorectal excision (TME).

14.
J Nat Prod ; 84(2): 483-494, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33544615

RESUMO

Twelve new hypothemycin-type resorcylic acid lactones, three 10-membered (1-3) and nine 14-membered (4-12), together with seven known analogues (13-19), were obtained from the solid rice-based culture of Podospora sp. G214. Their structures were elucidated utilizing spectroscopic analysis, and the absolute configurations were determined by modified Mosher's method, Mo2(OAc)4-induced electronic circular dichroism experiments, and single-crystal X-ray diffraction. Compounds 1, 5, 10, and 12-19 exhibited potent immunosuppressive activities against concanavalin A-induced T cell proliferation with IC50 values ranging from 6.0 to 25.1 µM and lipopolysaccharide-induced B cell proliferation with IC50 values ranging from 6.2 to 29.1 µM. Further studies revealed that 1 induced apoptosis in activated T cells through the JNK-mediated mitochondrial pathway.


Assuntos
Linfócitos B/efeitos dos fármacos , Imunossupressores/farmacologia , Lactonas/farmacologia , Podospora/química , Linfócitos T/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , China , Imunossupressores/isolamento & purificação , Lactonas/isolamento & purificação , Masculino , Camundongos Endogâmicos BALB C , Estrutura Molecular , Raízes de Plantas/microbiologia , Sanguisorba/microbiologia , Baço/citologia , Zearalenona/análogos & derivados , Zearalenona/isolamento & purificação , Zearalenona/farmacologia
15.
RSC Adv ; 11(41): 25738-25751, 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35478872

RESUMO

A series of novel piperine-resveratrol hybrids 5a-h was designed, synthesized, and structurally elucidated by IR, and 1H, 13C, and 19F NMR. Antiproliferative activities of 5a-h were evaluated by NCI against sixty cancer cell lines. Compound 5b, possessing resveratrol pharmacophoric phenolic moieties, showed a complete cell death against leukemia HL-60 (TB) and Breast cancer MDA-MB-468 with growth inhibition percentage of -0.49 and -2.83, respectively. In addition, 5b recorded significant activity against the other cancer cell lines with growth inhibition percentage between 80 to 95. New 5a-h hybrids were evaluated for their inhibitory activities against Sirt-1 and Sirt-2 as molecular targets for their antiproliferative action. Results showed that compounds 5a-h were more potent inhibitors of Sirt-2 than Sirt-1 at 5 µm and 50 µm. Compound 5b showed the strongest inhibition of Sirt-2 (78 ± 3% and 26 ± 3% inhibition at 50 µM and 5 µM, respectively). Investigation of intermolecular interaction via Hirschfeld surface analysis indicates that these close contacts are mainly ascribed to the O-H⋯O hydrogen bonding. To get insights into the Sirt-2 inhibitory mechanism, a docking study was performed where 5b was found to fit nicely inside both extended C-pocket and selectivity pocket and could compete with the substrate acyl-Lys. Another possible binding pattern showed that 5b could act by partial occlusion of the NAD+ C-pocket. Collectively, these findings would contribute significantly to better understanding the Sirt-2 inhibitory mechanism in order to develop a new generation of refined and selective Sirt-2 inhibitors.

16.
J Infect Dev Ctries ; 14(10): 1217-1220, 2020 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-33175720

RESUMO

INTRODUCTION: In some developing countries, tuberculosis and brucellosis, which are commom causes of spinal infections, are still common infectious diseases. However, co-occurrence of spinal tuberculosis and brucellosis is rare. METHODOLOGY: We report a case a 47-year-old male engaged in aquaculture with a medical history of numbness, weakness, fever, and night sweats in both upper limbs for about 10 days. Serum agglutination test (SAT) for Brucella revealed brucella infection. Cervical computed tomography (CT) scan and magnetic resonance imaging (MRI) suggested C6, C7 vertebral destruction and corresponding segmental nerve compression. Based on preoperative clinical symptoms and auxiliary examination, brucellar spondylitis was first suspected. According to the postoperative pathological examination, the patient was finally diagnosed as cervical spinal tuberculosis combined with brucellosis. RESULTS: The preoperative symptoms of the patient decreased significantly after surgery, and the patient recovered and leaved hospital within two weeks of starting treatment. At the 6-month follow-up, the patient's clinical symptoms completely disappeared, and all laboratory tests returned to normal. CONCLUSION: Cervical spinal tuberculosis combined with brucellosis is a relatively rare condition. In areas with high rates of tuberculosis and brucellosis, we should conduct comprehensive examinations to avoid misdiagnosis and missed diagnosis.


Assuntos
Brucelose/diagnóstico , Coinfecção/diagnóstico , Espondilite/microbiologia , Tuberculose da Coluna Vertebral/diagnóstico , Coinfecção/microbiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Espondilite/diagnóstico por imagem , Espondilite/cirurgia , Tomografia Computadorizada por Raios X
17.
J Nat Prod ; 83(5): 1505-1514, 2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32323537

RESUMO

Twelve new resorcylic acid lactones (RALs) including three new 16-membered RALs (1a, 1b and 2), eight new 14-membered RALs (3-10), and one new 12-membered RAL (11), along with five known 14-membered RALs (12-16), were identified from the fermentation of the soil-derived fungus Ilyonectria sp. sb65. Their structures were established by detailed analyses of 1D and 2D NMR, HRESIMS, and X-ray diffraction crystallography. All new compounds were evaluated for their cytotoxic effects against three human cancer cell lines, along with their potential as TRAIL sensitizers in TRAIL-resistant A549 human lung adenocarcinoma cells and their in vitro immunosuppressive effects against ConA-induced T-cell and LPS-induced B-cell proliferation.


Assuntos
Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacologia , Hypocreales/química , Lactonas/química , Lactonas/farmacologia , Resorcinóis/química , Animais , Linhagem Celular Tumoral , Cristalografia por Raios X , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Fermentação , Células HeLa , Humanos , Imunossupressores/farmacologia , Espectroscopia de Ressonância Magnética , Masculino , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Resorcinóis/farmacologia
18.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 34(3): 399-403, 2020 Mar 15.
Artigo em Chinês | MEDLINE | ID: mdl-32174090

RESUMO

OBJECTIVE: To review the research progress of the role and mechanism of adipokines in intervertebral disc degeneration (IVDD) in recent years. METHODS: The domestic and foreign literature related to adipokines in the process of IVDD was extensively reviewed. The types and functions of adipokines, the role and mechanism in the process of IVDD, and the application prospects of intervertebral disc biotherapy were reviewed. RESULTS: As a kind of bioactive substance secreted by adipose tissue, adipokine plays an important role in bone and joint diseases, metabolic diseases, and breast cancer. During IVDD, most adipokines can activate multiple signaling pathways by binding to autoreceptors, cause the proliferation and apoptosis of cells and proinflammatory and anti-inflammatory factors parasecretions in the intervertebral disc, and lead to imbalance of intradiscal metabolism and establishment of the initial inflammatory environment, and finally cause the IVDD. CONCLUSION: Adipokines, as a biologically active substance with metabolic and immunomodulatory functions, play important roles in the occurrence, development, and biological treatment of IVDD.


Assuntos
Adipocinas/fisiologia , Degeneração do Disco Intervertebral , Transdução de Sinais , Tecido Adiposo , Humanos , Disco Intervertebral
19.
Br J Radiol ; 93(1109): 20190571, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32017601

RESUMO

OBJECTIVE: (1) To evaluate the value of CT-guided microcoil implantation for localizing pulmonary ground-glass nodules (GGNs) before video-assisted thoracoscopic surgery (VATS). (2) To evaluate the feasibility, safety and accuracy of cephalic-caudal oblique approach for lesions difficult to access on axial images owing to overlying bony structures, large vessels or interlober fissures. METHODS: From June 2016 to March 2019, all patients with GGNs resected by VATS after marking using CT-guided microcoil implantation in China-Japan friendship hospital were enrolled and clinical and imaging data were retrospectively analyzed. According to the microcoil marked path, the GGNs were divided into cephalic-caudal oblique group (oblique group) and non-oblique group. The success rate of marking, the time required for marking and the incidence of complications between the two groups were compared. RESULTS: 258 GGNs from 215 consecutive patients were included in this study. The diameter of GGNs was 1.22 ± 0.50 cm, and the shortest distance from GGNs to the pleura was 1.56 ± 1.09 cm. All 258 GGNs were successfully resected by VATS under the guidance of implanted microcoils, and no case was converted to thoracotomy. During CT-guided microcoil implantation, cephalic- caudal oblique approach was taken in 56 GGNs (oblique group) to avoid bone, interlobar fissure and blood vessels. The time required for marking was significantly longer for oblique group compared with non-oblique group (16.6 ± 2.4 vs. 13.1 ± 1.9 min, p<0.01). No significant differences in the success rate of marking (94.6% vs 91.6%), the incidence of pneumothorax (19.6% vs 17.8%), the bleeding rate (10.7% vs 8.9%), and the hemoptysis rate (1.8% vs 1.5%) were observed between the two groups. CONCLUSION: CT-guided microcoil implantation can effectively guide VATS to resect GGNs. For GGNs difficult to access on axial images, CT-guided cephalic-caudal oblique approach is feasible, safe, and accurate. ADVANCES IN KNOWLEDGE: CT-guided microcoil implantation can effectively guide VATS to resect GGNs. The marked path with cephalic-caudal obliquity can effectively avoid bone, interlobar fissure and blood vessels, successfully mark GGNs difficult to access on axial images, while keeping the distance from the pleura to the lesion on the marked path as short as possible at the same time.


Assuntos
Neoplasias Pulmonares/cirurgia , Nódulos Pulmonares Múltiplos/cirurgia , Cirurgia Torácica Vídeoassistida/métodos , Estudos de Viabilidade , Feminino , Marcadores Fiduciais , Humanos , Masculino , Pessoa de Meia-Idade , Implantação de Prótese , Radiografia Intervencionista , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
20.
Clin Chim Acta ; 503: 151-156, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31978409

RESUMO

More and more evidence indicates that long non-coding RNAs (lncRNAs), as a kind of non-coding endogenous single-stranded RNA, play an essential role as oncogenes or tumour suppressors in the occurrence and development of human cancers. The tumour protein P73 antisense RNA 1 (TP73-AS1) was initially found to be down-regulated in oligodendroglioma and may act as a non-protein-encoding RNA. Since its discovery, TP73-AS1 has been identified as a carcinogenic regulator of many malignancies. At the same time, the high expression of TP73-AS1 is related to the clinicopathological features of patients with cancer. It also regulates cell proliferation, anti-apoptosis, invasion and metastasis through a variety of potential mechanisms, suggesting that it may be a promising biomarker and therapeutic target for cancer. In this review, we summarize the biological functions, mechanisms, and potential clinical implications of TP73-AS1 dysregulation in tumourigenesis and progression.


Assuntos
Neoplasias/genética , RNA Antissenso/fisiologia , RNA Longo não Codificante/fisiologia , Proteína Tumoral p73/genética , Apoptose , Carcinogênese/genética , Proliferação de Células , Progressão da Doença , Humanos , Invasividade Neoplásica , RNA Antissenso/metabolismo
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