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1.
JCI Insight ; 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35015734

RESUMO

The G-protein coupled C-X-C chemokine receptor 4 (CXCR4) is a candidate therapeutic target for tissue fibrosis. A novel fully human single-domain antibody-like scaffold i-body AD-114-PA600 (AD-114) with specific high binding affinity to CXCR4 has been developed. To define the renoprotective role, AD-114 was administrated in a mouse model of renal fibrosis induced by folic acid (FA). Increased extracellular matrix (ECM) accumulation, macrophage infiltration, inflammatory response, transforming growth factor beta-1 (TGF-ß1) expression and fibroblasts activation were observed in kidneys of mice with FA-induced nephropathy. These markers were normalized or partially reversed by AD-114 treatment. In vitro studies demonstrated AD-114 blocked TGF-ß1-induced upregulated expression of ECM, matrix metallopeptidase-2 (MMP-2) and downstream p38 mitogen-activated protein kinases (p38 MAPK) and Phosphoinositide 3-kinases (PI3K)/AKT/ mammalian target of rapamycin (mTOR) signaling pathways in a renal proximal tubular cell line. Additionally, these renoprotective effects were validated in a second model of unilateral ureteral obstruction (UUO) using a second generation of AD-114 (Fc-fused AD-114, also named AD-214). Collectively, these results suggest a renoprotective role of AD-114 as it inhibited the chemotactic function of CXCR4 as well as blocked CXCR4 downstream p38 MAPK and PI3K/AKT/mTOR signaling, which establish a therapeutic strategy for AD-114 targeting CXCR4 to limit renal fibrosis.

2.
Adv Sci (Weinh) ; : e2103829, 2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-34978158

RESUMO

Biomimetic mineralization based on self-assembly has made great progress, providing bottom-up strategies for the construction of new organic-inorganic hybrid materials applied in the treatment of hard tissue defects. Herein, inspired by the cooperative effects of key components in biomineralization microenvironments, a new type of biocompatible peptide scaffold based on flexibly self-assembling low-complexity protein segments (LCPSs) containing phosphate or phosphonate groups is developed. These LCPSs can retard the transformation of amorphous calcium phosphate into hydroxyapatite (HAP), leading to merged mineralization structures. Moreover, the application of phosphonated LCPS over phosphorylated LCPS can prevent hydrolysis by phosphatases that are enriched in extracellular mineralization microenvironments. After being coated on the etched tooth enamel, these LCPSs facilitate the growth of HAP to generate new enamel layers comparable to the natural layers and mitigate the adhesion of Streptococcus mutans. In addition, they can effectively stimulate the differentiation pathways of osteoblasts. These results shed light on the potential biomedical applications of two LCPSs in hard tissue repair.

3.
Lancet Reg Health West Pac ; 18: 100331, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35024660

RESUMO

Background: The national epidemiologic data in mainland China is still absent for moyamoya disease (MMD). Methods: This study was a nationwide hospital-based observational retrospective study to estimate epidemiological characteristics of MMD. The data was based on the Hospital Quality Monitoring System (HQMS), a national database which covers all tertiary hospitals in mainland China. This system consistently collects medical records including demographic characteristics, diagnoses, procedures, and expenses etc. for all inpatients. MMD was identified by ICD-10 code (I67·5) in HQMS. Findings: A total of 47,443 new-onset patients with total 69,680 hospitalization records from 1312 hospitals during 2016 to 2018 were included. The annual incidence rate was 1·14 per 100,000 inhabitants (95% CI, 1·12-1·16) and approximately a 2-fold increase from 2016 to 2018. The incidence in children (0·18 per 100,000 inhabitants per year; 95% CI, 0·17-0·20) was significantly lower than that in adults (1·40 per 100,000; 95% CI, 1·38-1·42) (P<0·001) and the peak incidence was 45-54 years. The distribution model of incidence rate was presented as a clustered regional pattern (Moran's I = 0·155, P = 0·018, Z = 2·375) by global spatial correlation analysis. Interpretation: Our study reported the annual incidence of MMD was 1·14 per 100,000 inhabitants in mainland China during 2016 to 2018, and it was increasing year by year. The geographical distribution of MMD incidence presented as a clustered regional pattern, which may provide new view for future study on the etiology for MMD. Funding: National Natural Science Foundation of China and "13th Five-Year Plan" National Science and Technology Supporting Plan.

4.
Sci Total Environ ; : 153079, 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35033571

RESUMO

Extreme temperature and precipitation indices have important implications for the crop growing season. Whether a coupled regional model with carbon-nitrogen cycling (CN) and vegetation dynamics (DV) can better represent these indices during the growing season compared with a model without these modules remains unknown. This study evaluates the performance of extreme indices in three wheat planting regions (including northeast spring wheat, north winter wheat and south winter wheat regions) over China in the period of 1990-2009 using the Regional Climate Model (RegCM) coupled with the Community Land Model (CLM), which include CN and DV. The results show that relative to the RegCM-CLM, both the RegCM-CLM-CN and RegCM-CLM-CN-DV perform better in simulating summer days (SU), consecutive dry days (CDD), consecutive wet days (CWD), and the interannual variability in all the extreme indices in the three regions but produce larger biases on frost days (FD). The trends of extreme indices in the high-impact risk region of wheat are also better captured by the RegCM-CLM with CN or CN-DV compared with the model without these modules. In the northeast spring wheat and southern winter wheat regions, the greater cold bias of mean daily minimum temperature between RegCM-CLM-CN-DV and RegCM-CLM is consistent with the leaf area index (LAI) difference, which may increase evaporative cooling and thus increasing FD biases. Overestimation of the LAI may have a weaker effect than the surface albedo on the mean daily maximum temperature, leading to decreased SU biases in RegCM-CLM-CN-DV relative to RegCM-CLM.

5.
ACS Nano ; 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35023720

RESUMO

Abnormal metabolism of cancer cells results in complex tumor microenvironments (TME), which play a dominant role in tumor metastasis. Herein, self-delivery ternary bioregulators (designated as TerBio) are constructed for photodynamic amplified immunotherapy against colorectal cancer by TME reprogramming. Specifically, carrier-free TerBio are prepared by the self-assembly of chlorine e6, SB505124 (SB), and lonidamine (Lon), which exhibit improved tumor accumulation, tumor penetration, and cellular uptake behaviors. Interestingly, TerBio-mediated photodynamic therapy (PDT) could not only inhibit the primary tumor growth but also induce immunogenic cell death of tumors to activate the cascade immune response. Furthermore, TerBio are capable of TME reprograming by SB-triggered transforming growth factor (TGF)-ß blockage and Lon-induced lactic acid efflux inhibition. As a consequence, TerBio significantly suppresses distant and metastatic tumor growth by PDT-amplified immunotherapy. This study might advance the development of self-delivery nanomedicine against malignant tumor growth and metastasis.

6.
BMC Infect Dis ; 22(1): 26, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983430

RESUMO

BACKGROUND: Early diagnosis and treatment of patients with sepsis reduce mortality significantly. In terms of exploring new diagnostic tools of sepsis, monocyte distribution width (MDW), as part of the white blood cell (WBC) differential count, was first reported in 2017. MDW greater than 20 and abnormal WBC count together provided a satisfactory accuracy and was proposed as a novel diagnostic tool of sepsis. This study aimed to compare MDW and procalcitonin (PCT)'s diagnostic accuracy on sepsis in the emergency department. METHODS: This was a single-center prospective cohort study. Laboratory examinations including complete blood cell and differentiation count (CBC/DC), MDW, PCT were obtained while arriving at the ED. We divided patients into non-infection, infection without systemic inflammatory response syndrome (SIRS), infection with SIRS, and sepsis-3 groups. This study's primary outcome is the sensitivity and specificity of MDW, PCT, and MDW + WBC in differentiating septic and non-septic patients. In addition, the cut-off value for MDW was established to maximize sensitivity at an optimal level of specificity. RESULTS: From May 2019 to September 2020, 402 patients were enrolled for data analysis. Patient number in each group was: non-infection 64 (15.9%), infection without SIRS 82 (20.4%), infection with SIRS 202 (50.2%), sepsis-3 15 (7.6%). The AUC of MDW, PCT, and MDW + WBC to predict infection with SIRS was 0.753, 0.704, and 0.784, respectively (p < 0.01). The sensitivity, specificity, PPV, and NPV of MDW using 20 as the cutoff were 86.4%, 54.2%, 76.4%, and 70%, compared to 32.9%, 88%, 82.5%, and 43.4% using 0.5 ng/mL as the PCT cutoff value. On combing MDW and WBC count, the sensitivity and NPV further increased to 93.4% and 80.3%, respectively. In terms of predicting sepsis-3, the AUC of MDW, PCT, and MDW + WBC was 0.72, 0.73, and 0.70, respectively. MDW, using 20 as cutoff, exhibited sensitivity, specificity, PPV, and NPV of 90.6%, 37.1%, 18.7%, and 96.1%, respectively, compared to 49.1%, 78.6%, 26.8%, and 90.6% when 0.5 ng/mL PCT was used as cutoff. CONCLUSIONS: In conclusion, MDW is a more sensitive biomarker than PCT in predicting infection-related SIRS and sepsis-3 in the ED. MDW < 20 shows a higher NPV to exclude sepsis-3. Combining MDW and WBC count further improves the accuracy in predicting infection with SIRS but not sepsis-3. Trial registration The study was retrospectively registered to the ClinicalTrial.gov (NCT04322942) on March 26th, 2020.


Assuntos
Pró-Calcitonina , Sepse , Biomarcadores , Proteína C-Reativa/análise , Serviço Hospitalar de Emergência , Humanos , Monócitos , Estudos Prospectivos , Sepse/diagnóstico
7.
BMJ Open ; 12(1): e051888, 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35027417

RESUMO

OBJECTIVE: To evaluate the healthcare resource utilisation for chronic kidney disease (CKD) and other major non-communicable chronic diseases (NCDs) in China. DESIGN: A cross-sectional study. SETTING: A national inpatient database of tertiary hospitals in China. PARTICIPANTS: The study included a total of 19.5 million hospitalisations of adult patients from July 2013 to June 2014. Information on CKD and other major NCDs, including coronary heart disease (CHD), stroke, hypertension, diabetes, chronic obstructive pulmonary disease (COPD) and cancer, was extracted from the unified discharge summary form. OUTCOME MEASURES: Cost, length of hospital stay and in-hospital mortality. RESULTS: The percentages of hospitalisations with CKD, CHD, stroke, hypertension, diabetes, COPD and cancer were 4.5%, 9.2%, 8.2%, 18.8%, 7.9%, 2.3% and 19.4%, respectively. For each major NCD, the presence of CKD was independently associated with longer hospital stay, with increased percentages ranging from 7.69% (95% CI 7.11% to 8.28%) for stroke to 21.60% (95% CI 21.09% to 22.10%) for CHD. Hospital mortality for other NCDs was also higher in the presence of CKD, with fully adjusted relative risk ranging from 1.91 (95% CI 1.82 to 1.99) for stroke to 2.65 (95% CI 2.55 to 2.75) for cancer. Compared with other NCDs, CKD was associated with the longest hospital stay (22.1% increase) and resulted in the second highest in-hospital mortality, only lower than that of cancer (relative risk, 2.23 vs 2.87, respectively). CONCLUSIONS: The presence of diagnosed CKD alongside each major NCD was associated with an additional burden on the healthcare system. Healthcare resource utilisation and prognosis of CKD were comparable with those of other major NCDs, which highlights the importance of CKD as a major public health burden.

9.
Am J Dermatopathol ; 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34991099

RESUMO

ABSTRACT: Cutaneous leukocytoclastic vasculitis (CLV) is a vasculitis that involves mainly small blood vessels in the skin. CLV has different causes (drugs, infections, or neoplastic or systemic inflammatory diseases). Sporotrichosis has rarely been associated with CLV. We report a case of disseminated cutaneous sporotrichosis caused by microorganisms in the Sporothrix clade in a Chinese woman with a tuberculous peritonitis history. Her lesions included many ulcers with crusts on the limbs. A skin biopsy yielded a histologic diagnosis of leukocytoclastic vasculitis. Periodic acid-Schiff and Grocott methenamine silver stains revealed numerous round-to-oval, thick-walled yeast cells in the necrotic tissue of the dermis. Mycological cultures grew pure dark brown wrinkled and villous fungus colonies morphologically and microscopic characteristics suggestive of the pathogenic Sporothrix clade which was followed confirmed as Sporothrix globosa (S. globosa) by the PCR method and sequencing based on calmodulin gene. Although infrequently, Sporothrix clade may cause CLV and should be considered in its differential diagnosis.

10.
J Hazard Mater ; 423(Pt A): 127052, 2022 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-34523492

RESUMO

6:2 fluorotelomer sulfonic acid (6:2 FTSA) is one per- and poly-fluoroalkyl substances commonly detected in the environment. While biotransformation of 6:2 FTSA has been reported, factors affecting desulfonation and defluorination of 6:2 FTSA remain poorly understood. This study elucidated the effects of carbon and sulfur sources on the gene expression of Rhodococcus jostii RHA1 which is responsible for the 6:2 FTSA biotransformation. While alkane monooxygenase and cytochrome P450 were highly expressed in ethanol-, 1-butanol-, and n-octane-grown RHA1 in sulfur-rich medium, these cultures only defluorinated 6:2 fluorotelomer alcohol but not 6:2 FTSA, suggesting that the sulfonate group in 6:2 FTSA hinders enzymatic defluorination. In sulfur-free growth media, alkanesulfonate monooxygenase was linked to desulfonation of 6:2 FTSA; while alkane monooxygenase, haloacid dehalogenase, and cytochrome P450 were linked to defluorination of 6:2 FTSA. The desulfonation and defluorination ability of these enzymes toward 6:2 FTSA were validated through heterologous gene expression and in vitro assays. Four degradation metabolites were confirmed and one was identified as a tentative metabolite. The results provide a new understanding of 6:2 FTSA biotransformation by RHA1. The genes encoding these desulfonating- and defluorinating-enzymes are potential markers to be used to assess 6:2 FTSA biotransformation in the environment.


Assuntos
Rhodococcus , Ácidos Sulfônicos , Carbono , Fluorcarbonetos , Rhodococcus/genética , Enxofre
11.
Spectrochim Acta A Mol Biomol Spectrosc ; 267(Pt 1): 120463, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34673324

RESUMO

The excited state dynamics processes of two diphenylamine substituted symmetric 1,3,4-oxadiazole derivatives in different solvents were studied through femtosecond transient absorption spectroscopy. It was revealed that in cyclohexane, the locally excited (LE) state relaxes to the intramolecular charge transfer (ICT) state within 2 ps timescale, then decays to the ground state. In tetrahydrofuran and acetonitrile, the ICT state can be stabilized via solvation, so besides the LE â†’ ICT conversion within 1 ps, another ICT â†’ solvent stabilized ICT (SSICT) conversion in the 1-200 ps time scale could also be observed, and eventually decay to the ground state. Whereas, ICT â†’ SSICT process in acetonitrile is slower than that in tetrahydrofuran, which leads to radiationless deactivation dominates the ICT state deactivation process and low fluorescence quantum efficiency. These results offer a guidance to understand the relationship of low fluorescence quantum efficiency and excited state deactivation mechanism of organic π-conjugated molecules, which would be very helpful for designing new advanced opto-electronic materials.


Assuntos
Difenilamina , Cinética , Oxidiazóis , Espectrometria de Fluorescência , Termodinâmica
12.
J Phys Chem Lett ; 13(1): 136-141, 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-34962404

RESUMO

Increasing aggregation induced emission (AIE) efficiency is of fundamental interest as it directly reflects performance of multitwist-based luminogens in bioimaging and in the photoelectric device field. However, an effective and convenient methodology to increase AIE efficiency significantly remains a challenge. Here, we present a general strategy to increase AIE efficiency of multitwist-based luminogens by pressure, resulting in a 120.1-fold enhancement of the AIE intensity of tris[4-(diethylamino)phenyl]amine (TDAPA) under high pressure compared to that of the traditional method. AIE efficiency of TDAPA increases from 0.5% to 46.1% during compression. Experimental and theoretical investigations reveal that the AIE efficiency enhancement originates from intramolecular vibration and the twisted intramolecular charge transfer are suppressed under high pressure. High AIE efficiency under high pressure provides an important inspiration for improving performance of multitwist-based luminogens in the lighting and biomedical fields.

13.
Neural Regen Res ; 17(7): 1588-1595, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34916445

RESUMO

Cellular senescence and proliferation are essential for wound healing and tissue remodeling. However, senescence-proliferation cell fate after peripheral nerve injury has not been clearly revealed. Here, post-injury gene expression patterns in rat sciatic nerve stumps (SRP113121) and L4-5 dorsal root ganglia (SRP200823) obtained from the National Center for Biotechnology Information were analyzed to decipher cellular senescence and proliferation-associated genetic changes. We first constructed a rat sciatic nerve crush model. Then, ß-galactosidase activities were determined to indicate the existence of cellular senescence in the injured sciatic nerve. Ki67 and EdU immunostaining was performed to indicate cellular proliferation in the injured sciatic nerve. Both cellular senescence and proliferation were less vigorous in the dorsal root ganglia than in sciatic nerve stumps. These results reveal the dynamic changes of injury-induced cellular senescence and proliferation from both genetic and morphological aspects, and thus extend our understanding of the biological processes following peripheral nerve injury. The study was approved by the Animal Ethics Committee of Nantong University, China (approval No. 20190226-001) on February 26, 2019.

14.
Food Chem ; : 131670, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34848083

RESUMO

Phenolic copigments have important influence on red wine color. In this study, UV-visible spectrophotometer and UHPLC-Q-TOF-MS were combined to investigate the effects of three types of phenolic copigments (gallic acid, (-)-epicatechin, and quercetin-3-O-glucoside) on the stability and color properties of five common 3-O-monoglucosidic anthocyanins in model wine solutions. Results showed low concentrations (0.5 mM) of gallic acid and (-)-epicatechin protected anthocyanins from degradation, whereas high concentrations (8 mM) of them had the opposite effect. Quercetin-3-O-glucoside always improved the stability of anthocyanins despite its additive amount (0.1 mM or 0.4 mM). Even small quantity of (-)-epicatechin led to obvious yellow hue into the solution, and xanthylium derivatives generated from (-)-epicatechin were detected. Antagonistic effect among the three copigments was observed, probably as a result of competition of intermolecular copigmentation. Additionally, the stability of anthocyanins was significantly influenced by their structures: cyanidin-3-O-glucoside, peonidin-3-O-glucoside, and malvidin-3-O-glucoside were more stable than delphinidin-3-O-glucoside and petunidin-3-O-glucoside.

15.
Neoplasma ; 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34881631

RESUMO

The aim of this research was to investigate the role of hyaluronan-binding protein 1 (HABP1) in lung adenocarcinoma. It was demonstrated by bioinformatics analysis that HABP1 was one of the differentially expressed genes in lung adenocarcinoma. Then, it was confirmed by qPCR, western blot, and immunohistochemistry analysis that HABP1 was upregulated in human tissue specimens we collected. Survival analysis showed that HABP1 was promised to serve as a new biomarker to predict the progress and prognosis of lung adenocarcinoma patients. In addition, we further studied the effects of regulating the expression of HABP1 on lung adenocarcinoma cells, indicating that altered expression of HABP1 could adjust cell proliferation and invasion through the NFκB signaling pathway.

16.
Metab Eng ; 69: 163-174, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34864212

RESUMO

The marine alga Nannochloropsis oceanica has been considered as a promising photosynthetic cell factory for synthesizing eicosapentaenoic acid (EPA), yet the accumulation of EPA in triacylglycerol (TAG) is restricted to an extreme low level. Poor channeling of EPA to TAG was observed in N. oceanica under TAG induction conditions, likely due to the weak activity of endogenous diacylglycerol acyltransferases (DGATs) on EPA-CoA. Screening over thirty algal DGATs revealed potent enzymes acting on EPA-CoA. Whilst overexpressing endogenous DGATs had no or slight effect on EPA abundance in TAG, introducing selected DGATs with strong activity on EPA-CoA, particularly the Chlamydomonas-derived CrDGTT1, which resided at the outermost membrane of the chloroplast and provided a strong pulling power to divert EPA to TAG for storage and protection, led to drastic increases in EPA abundance in TAG and TAG-derived EPA level in N. oceanica. They were further promoted by additional overexpression of an elongase gene involved in EPA biosynthesis, reaching 5.9- and 12.3-fold greater than the control strain, respectively. Our results together demonstrate the concept of applying combined pulling and pushing strategies to enrich EPA in algal TAG and provide clues for the enrichment of other desired fatty acids in TAG as well.

17.
Oxid Med Cell Longev ; 2021: 2502324, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34970414

RESUMO

Obstructive sleep apnea (OSA) is highly prevalent in patients with abdominal aortic aneurysm (AAA). However, the effects of OSA on AAA initiation in a murine model of sleep apnea have not been completely studied. In this paper, Apoe-/- C57BL/6 mice infused with angiotensin II (Ang II) were placed in chronic intermittent hypoxia (CIH) condition for inducing OSA-related AAA. CIH significantly promoted the incidence of AAA and inhibited the survival of mice. By performing ultrasonography and elastic Van Gieson staining, CIH was found to be effective in promoting aortic dilation and elastin degradation. Immunohistochemical and zymography results show that CIH upregulated the expression and activity of MMP2 and MMP9 and upregulated MCP1 expression while downregulating α-SMA expression. Also, CIH exposure promoted ROS generation, apoptosis, and mitochondria damage in vascular smooth muscle cells (VSMCs), which were measured by ROS assay, TUNEL staining, and transmission electron microscopy. The result of RNA sequencing of mouse aortas displayed that 232 mRNAs were differently expressed between Ang II and Ang II+CIH groups, and CaMKII-dependent p38/Jnk was confirmed as one downstream signaling of CIH. CaMKII-IN-1, an inhibitor of CaMKII, eliminated the effects of CIH on the loss of primary VSMCs. To conclude, a mouse model of OSA-related AAA, which contains the phenotypes of both AAA and OSA, was established in this study. We suggested CIH as a risk factor of AAA initiation through CaMKII-dependent MAPK signaling.

18.
J Immunother Cancer ; 9(12)2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34933967

RESUMO

BACKGROUND: This study aimed to evaluate the antitumor activity of camrelizumab, an antiprogrammed cell death-1 antibody, in pretreated recurrent or metastatic nasopharyngeal carcinoma (NPC) and to explore predictive biomarkers. METHODS: Patients with recurrent (not amenable to locally curative treatment) or metastatic NPC who had failed at least two lines of chemotherapy were eligible to receive camrelizumab (200 mg intravenously every 2 weeks) for 2 years or until disease progression, intolerable adverse events, withdrawal of consents, or investigator decision. The primary endpoint was objective response rate (ORR) assessed by an independent review committee (IRC). Programmed cell death-ligand 1 (PD-L1) expression was assessed by immunohistochemistry. Other immune-related biomarkers including major histocompatibility complex class I and major histocompatibility complex class II (MHC-II) were assessed by multiplex immunofluorescence staining. RESULTS: Between August 14, 2018, and December 30, 2019, a total of 156 patients were enrolled. The IRC-assessed ORR was 28.2% (95% CI 21.3% to 36.0%). The median progression-free survival was 3.7 months (95% CI 2.0 to 4.1) per IRC, and the median overall survival was 17.4 months (95% CI 15.2 to 21.9). The ORRs were 35.2% (95% CI 25.3% to 46.1%) vs 19.4% (95% CI 10.4% to 31.4%) in patients with tumor PD-L1 expression of ≥10% and<10%, respectively. Patients with durable clinical benefit (DCB), which was defined as complete response, partial response or stable disease of ≥18 weeks, had higher density of MHC-II+ cell in stroma than patients without DCB (median 868.1 (IQR 413.4-2854.0) cells/mm2 vs median 552.4 (IQR 258.4 to 1242.1) cells/mm2). MHC-II+ cell density did not correlate with PD-L1 expression, and a composite of high stromal MHC-II+ cell density and tumor PD-L1 expression further enriched patients who could benefit from camrelizumab. CONCLUSIONS: Camrelizumab had clinically meaningful antitumor activity in patients with recurrent or metastatic NPC. The composition of both MHC-II+ cell density and PD-L1 expression could result in better patient selection.

19.
Front Immunol ; 12: 752657, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34899703

RESUMO

Mycobacteriosis, mostly resulting from Mycobacterium tuberculosis (MTb), nontuberculous mycobacteria (NTM), and Mycobacterium leprae (M. leprae), is the long-standing granulomatous disease that ravages several organs including skin, lung, and peripheral nerves, and it has a spectrum of clinical-pathologic features based on the interaction of bacilli and host immune response. Histiocytes in infectious granulomas mainly consist of infected and uninfected macrophages (Mφs), multinucleated giant cells (MGCs), epithelioid cells (ECs), and foam cells (FCs), which are commonly discovered in lesions in patients with mycobacteriosis. Granuloma Mφ polarization or reprogramming is the crucial appearance of the host immune response to pathogen aggression, which gets a command of endocellular microbe persistence. Herein, we recapitulate the current gaps and challenges during Mφ polarization and the different subpopulations of mycobacteriosis.

20.
J Cell Mol Med ; 2021 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-34935260

RESUMO

Islet ß cell dedifferentiation is one of the most important mechanisms in the occurrence and development of diabetes. We studied the possible effects of chemokine stromal cell-derived factor-1 (SDF-1) in the dedifferentiation of islet ß cells. It was noted that the number of dedifferentiated islet ß cells and the expression of SDF-1 in pancreatic tissues significantly increased with diabetes. In islet ß cell experiments, inhibition of SDF-1 expression resulted in an increase in the number of dedifferentiated cells, while overexpression of SDF-1 resulted in a decrease. This seemed to be contradicted by the effect of diabetes on the expression of SDF-1 in pancreatic tissue, but it was concluded that this may be related to the loss of SDF-1 activity. SDF-1 binds to CXCR4 to form a complex, which activates and phosphorylates AKT, subsequently increases the expression of forkhead box O1 (FOXO1), and inhibits the dedifferentiation of islet ß cells. This suggests that SDF-1 may be a novel target in the treatment of diabetes.

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