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1.
Biol Pharm Bull ; 45(1): 27-33, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34980778

RESUMO

This study aimed to explore the effect of curcumin and hydromorphone hydrochloride (HH) cotreatment on postoperative pain in rats. An incision + formaldehyde-induced pain rat model was established. Rats were treated with vehicle, curcumin, HH, or curcumin + HH. Paw mechanical withdrawal threshold and thermal withdrawal latency were measured at 1 d before surgery as well as 1 , 2 h, 1 , 3 , and 7 d after surgery to assess pain sensitivity. The L4-6 region of the spinal cord was collected from each rat at 2 h, 1 , 3 , and 7 d after surgery. Western blot analysis and immunohistochemical staining were carried out to detect the protein expression of pain-related genes. Quantitative real-time PCR and enzyme-linked immunosorbent assay were conducted to measure the expression and production of proinflammatory mediators. Compared with other groups, Curcumin + HH significantly reduced pain sensitivity in the model rats. Mechanistically, curcumin + HH suppressed protein expression of stromal cell-derived factor-1 (SDF-1), CXC chemokine receptor 4 (CXCR4), p-Akt, and c-fos while enhancing protein expression of nerve growth factor (NGF) in the dorsal root ganglia (DRG) of model rats. Curcumin + HH inhibited the expression and production of interleukin 1ß (IL-1ß), cyclooxygenase-2 (COX-2), tumor necrosis factor α (TNF-α), and p65 nuclear factor kappa B (NF-κB) in the DRG. Coadministration of curcumin and HH alleviates incision + formaldehyde-induced pain in rats, possibly by suppressing the SDF-1/CXCR4 pathway and the production of proinflammatory mediators. Our results provide curcumin and HH cotreatment as a promising therapeutic strategy in the management of postoperative pain.

2.
Microb Cell Fact ; 20(1): 227, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34930257

RESUMO

BACKGROUND: The various advantages associated with the growth properties of Escherichia coli have justified their use in the production of genetically engineered vaccines. However, endotoxin contamination, plasmid vector instability, and the requirement for antibiotic supplementation are frequent bottlenecks in the successful production of recombinant proteins that are safe for industrial-scaled applications. To overcome these drawbacks, we focused on interrupting the expression of several key genes involved in the synthesis of lipopolysaccharide (LPS), an endotoxin frequently responsible for toxicity in recombinant proteins, to eliminate endotoxin contamination and produce better recombinant proteins with E. coli. RESULTS: Of 8 potential target genes associated with LPS synthesis, we successfully constructed 7 LPS biosynthesis-defective recombinant strains to reduce the production of LPS. The endotoxin residue in the protein products from these modified E. coli strains were about two orders of magnitude lower than that produced by the wild-type strain. Further, we found that 6 loci-lpxM, lpxP, lpxL, eptA, gutQ and kdsD-were suitable for chromosomal integrated expression of HPV L1 protein. We found that a single copy of the expression cassette conferred stable expression during long-term antibiotic-free cultivation as compared with the more variable protein production from plasmid-based expression. In large-scale fermentation, we found that recombinant strains bearing 3 to 5 copies of the expression cassette had 1.5- to 2-fold higher overall expression along with lower endotoxin levels as compared with the parental ER2566 strain. Finally, we engineered and constructed 9 recombinant E. coli strains for the later production of an HPV 9-valent capsid protein with desirable purity, VLP morphology, and antigenicity. CONCLUSIONS: Reengineering the LPS synthesis loci in the E. coli ER2566 strain through chromosomal integration of expression cassettes has potential uses for the production of a 9-valent HPV vaccine candidate, with markedly reduced residual endotoxin levels. Our results offer a new strategy for recombinant E. coli strain construction, engineering, and the development of suitable recombinant protein drugs.

3.
Cornea ; 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34759200

RESUMO

PURPOSE: The purpose of this study was to assess the distribution and morphological variation of conjunctiva-associated lymphoid tissue (CALT) in healthy human subjects and patients with meibomian gland dysfunction (MGD) using laserscanningin vivo confocal microscopy. METHODS: A total of 34 healthy subjects and 32 patients with MGD were enrolled. All subjects underwent a conventional examination consisting of slitlamp biomicroscopy, tear film break-up time, and the Schirmer test. In vivo microscopy was applied to analyze the morphological changes in the diffuse lymphoid layer and lymphoid follicles in CALT. Conjunctival impression cytology (CIC) of samples of patients' palpebral conjunctiva and immunofluorescence staining of CD4 and CD8 antibodies were also performed to indicate the immune response status of CALT. RESULTS: In the MGD group, the density of diffuse lymphocytes (P < 0.001), follicles (P < 0.001), and perifollicular lymphocytes was higher (P < 0.001) and the central reflection of the follicles was stronger (P < 0.001) than in the control group, while there was no difference in the follicle area (P = 0.758). Besides, diffuse lymphocyte density was correlated with telangiectasia, and follicular center reflection intensity was correlated with plugging. CIC immunofluorescence staining showed a higher percentage of CD4+ (P < 0.001) and CD8+ (P < 0.001) cells in the MGD group than in the control group. CONCLUSIONS: Using laser scanning in vivo confocal microscopy and CIC immunofluorescence staining, we observed the activation of CALT in patients with MGD, and some CALT-related parameters correlated with the lid margin findings of patients with MGD.

4.
Chem Sci ; 12(34): 11548-11553, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34667557

RESUMO

The visible-light-driven photoreduction of CO2 to value-added chemicals over metal-free photocatalysts without sacrificial reagents is very interesting, but challenging. Herein, we present amide-bridged conjugated organic polymers (amide-COPs) prepared via self-condensation of amino nitriles in combination with hydrolysis, for the photoreduction of CO2 with H2O without any photosensitizers or sacrificial reagents under visible light irradiation. These catalysts can afford CO as the sole carbonaceous product without H2 generation. Especially, amide-DAMN derived from diaminomaleonitrile exhibited the highest activity for the photoreduction of CO2 to CO with a generation rate of 20.6 µmol g-1 h-1. Experiments and DFT calculations confirmed cyano/amide groups as active sites for CO2 reduction and second amine groups for H2O oxidation, and suggested that superior selectivity towards CO may be attributed to the adjacent redox sites. This work presents a new insight into designing photocatalysts for artificial photosynthesis.

5.
Eye (Lond) ; 2021 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-34689182

RESUMO

PURPOSE: To assess the morphologic and clinical features of posterior capsule-intraocular lens (IOL) interaction following cataract surgery with and without primary posterior continuous curvilinear capsulorrhexis (PPCCC) at a three-dimensional (3-D) level using Scheimpflug imaging. METHODS: This prospective intraindividual randomized comparative study comprised 56 patients (112 eyes) with age-related cataract who had bilateral cataract surgery and hydrophobic acrylic IOLs implantation. In randomized order, cataract surgery with PPCCC was performed in 1 eye (PPCCC group), and the posterior capsule was left intact in the fellow eye (NPCCC group). Scheimpflug imaging containing 25 images distributed in 360° was taken 1 day, 1 week, 1 month, and 3 months postoperatively. RESULTS: 46 patients completed 3 months follow-up. Posterior capsule-IOL interaction can be morphologically classified into two types including complete adhesion and floppy shape in PPCCC group, and six types including full area wave, full area flat, concentric ring wave, concentric ring flat, sector, and complete adhesion in NPCCC group. The adhesion index (AI), defined as the proportion of complete adhesion of posterior capsule-IOL in 25 cross-section tomograms, was 0.45 ± 0.45, 0.79 ± 0.37, 0.92 ± 0.26 and 1.00 ± 0.00 in PPCCC group, while 0.05 ± 0.18, 0.41 ± 0.47, 0.87 ± 0.34, and 0.96 ± 0.21 in NPCCC group at 1 day, 1 week, 1 month and 3 months postoperatively, respectively (p = 0.001, 0.001, 0.338 and 0.151). CONCLUSIONS: 3-D Scheimpflug imaging was favorable in observing of posterior capsule-IOL interaction. Faster posterior capsule adhesion to the IOL was found in PPCCC group than in NPCCC group.

6.
Dalton Trans ; 50(43): 15849-15854, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34708848

RESUMO

Uniform lithium deposition is a benefit to achieving high-energy-density lithium metal batteries. There are many effective methods to suppress the dendritic growth of metallic lithium and promote the application of the lithium anode. However, the designation of lithiophilic sites at the atomic level remains a huge challenge. Herein, a two-dimensional porous conjugated porphyrin polymer linked by two acetylenic linkages from an in situ coupling reaction has been prepared on copper foil and employed as the lithiophilic host. The four electron-rich pyrrolic nitrogen atoms in the porphyrin building block and the linkage electron-rich sp-hybridized carbon atoms were regarded as precise lithiophilic sites, resulting in a decreased nucleation overpotential and dendrite free morphology. With uniform lithium deposition, the electrochemical performance of the electrode was significantly improved in regard to the overpotential, coulombic efficiency and lifespan. This work expands the precise construction of lithiophilic sites at the atomic level and benefits to further development of high-energy density lithium metal batteries.

7.
Front Cell Infect Microbiol ; 11: 693981, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34504806

RESUMO

Objective: Macrophages function as key orchestrators in the pathogenesis of acute lung injury (ALI). The current study sets out to investigate the molecular mechanism of transforming growth factor-ß (TGFß1) in the regulation of M1 alveolar macrophage polarization in ALI by modulating DNA methyltransferase 1 (DNMT1), along with the microRNA (miR)-124/Pellino 1 (PELI1)/interferon regulatory factor 5 (IRF5) axis. Methods: First, ALI mouse models were established, and the proportion of M1 and M2 macrophages in mouse lung tissues was detected using flow cytometry. The targeting relationship between miR-124 and PELI1 was verified with the help of a dual luciferase gene reporter assay. Following TGFß1 knockdown, RT-qPCR and Western blot assay were performed to analyze the expression patterns of TGFß1, DNMT1, miR-124, and PELI1 and M1/M2 polarization markers in the lung tissues of ALI mice. Immunofluorescence was further employed to detect nuclear translocation of IRF5 in macrophages. Results: The polarization of M1 macrophages was found to be positively correlated with the severity of lung injury. TGFß1, DNMT1, PELI1 were highly expressed, while miR-124 was down-regulated in ALI mice, and IRF5 was primarily distributed in the nucleus. TGFß1 promoted the polarization of M1 alveolar macrophages by up-regulating DNMT1. Furthermore, DNMT1 down-regulated the expression of miR-124, which led to enhancement of M1 alveolar macrophage polarization. Meanwhile, over-expression of miR-124 inhibited the nuclear translocation of IRF5 and suppressed M1 alveolar macrophage polarization. On the other hand, over-expression of PELI1 reversed the above trends. Conclusion: Collectively, our findings indicated that TGFß1 can promote the expression of DNMT1, which down-regulates miR-124 to activate PELI1 and nuclear translocation of IRF5, thereby aggravating ALI in mice.


Assuntos
Lesão Pulmonar Aguda , MicroRNAs , Animais , Fatores Reguladores de Interferon/genética , Macrófagos/metabolismo , Macrófagos Alveolares , Camundongos , MicroRNAs/genética , Proteínas Nucleares , Fator de Crescimento Transformador beta1 , Ubiquitina-Proteína Ligases
8.
Nat Commun ; 12(1): 5652, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34580306

RESUMO

The emergence of numerous variants of SARS-CoV-2, the causative agent of COVID-19, has presented new challenges to the global efforts to control the COVID-19 pandemic. Here, we obtain two cross-neutralizing antibodies (7D6 and 6D6) that target Sarbecoviruses' receptor-binding domain (RBD) with sub-picomolar affinities and potently neutralize authentic SARS-CoV-2. Crystal structures show that both antibodies bind a cryptic site different from that recognized by existing antibodies and highly conserved across Sarbecovirus isolates. Binding of these two antibodies to the RBD clashes with the adjacent N-terminal domain and disrupts the viral spike. Both antibodies confer good resistance to mutations in the currently circulating SARS-CoV-2 variants. Thus, our results have direct relevance to public health as options for passive antibody therapeutics and even active prophylactics. They can also inform the design of pan-sarbecovirus vaccines.


Assuntos
Anticorpos Antivirais/imunologia , Anticorpos Amplamente Neutralizantes/imunologia , COVID-19/terapia , Imunização Passiva/métodos , SARS-CoV-2/imunologia , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/isolamento & purificação , Anticorpos Monoclonais/metabolismo , Anticorpos Antivirais/administração & dosagem , Anticorpos Antivirais/isolamento & purificação , Anticorpos Antivirais/metabolismo , Sítios de Ligação/genética , Sítios de Ligação/imunologia , Anticorpos Amplamente Neutralizantes/administração & dosagem , Anticorpos Amplamente Neutralizantes/isolamento & purificação , Anticorpos Amplamente Neutralizantes/metabolismo , Células CHO , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/virologia , Chlorocebus aethiops , Cricetulus , Epitopos/imunologia , Células HEK293 , Humanos , Camundongos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Testes de Neutralização , Pandemias/prevenção & controle , Multimerização Proteica , Receptores Virais/metabolismo , SARS-CoV-2/genética , Células Sf9 , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Células Vero
9.
Virol Sin ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34581960

RESUMO

Coxsackievirus B1 (CVB1) is a leading causative agent of severe infectious diseases in humans and has been reported to be associated with outbreaks of aseptic meningitis, myocarditis, and the development of chronic diseases such as type 1 diabetes mellitus (T1DM). There is no approved vaccine or effective antiviral therapy to treat CBV1 infection. And animal models to assess the effects of antiviral agents and vaccine remain limited. In this study, we established a neonatal mouse model of CVB1 using a clinically isolated strain to characterize the pathological manifestations of virus infection and to promote the development of vaccines and antiviral drugs against CVB1. One-day-old BALB/c mice were susceptible to CVB1 infection by intraperitoneal injection. Mice challenged with CVB1 at a low dose [10 median tissue culture infective dose (TCID50)] exhibited a series of clinical symptoms, such as inactivity, emaciation, limb weakness, hair thinning, hunching and even death. Pathological examination and tissue viral load analysis showed that positive signals of CVB1 were detected in the heart, spinal cord, limb muscle and kidney without pathological damage. Particularly, CVB1 had a strong tropism towards the pancreas, causing severe cellular necrosis with inflammatory infiltration, and was spread by viraemia. Notably, the monoclonal antibody (mAb) 6H5 and antisera elicited from CVB1-vaccinated mice effectively protected the mice from CVB1 infection in the mouse model. In summary, the established neonatal mouse model is an effective tool for evaluating the efficacy of CVB1 antiviral reagents and vaccines.

10.
Vaccines (Basel) ; 9(8)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34451954

RESUMO

To date, SARS-CoV-2 pandemic has caused more than 188 million infections and 4.06 million deaths worldwide. The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein has been regarded as an important target for vaccine and therapeutics development because it plays a key role in binding the human cell receptor ACE2 that is required for viral entry. However, it is not easy to detect RBD in Western blot using polyclonal antibody, suggesting that RBD may form a complicated conformation under native condition and bear rare linear epitope. So far, no linear epitope on RBD is reported. Thus, a monoclonal antibody (mAb) that recognizes linear epitope on RBD will become valuable. In the present study, an RBD-specific rabbit antibody named 9E1 was isolated from peripheral blood mononuclear cells (PBMC) of immunized rabbit by RBD-specific single B cell sorting and mapped to a highly conserved linear epitope within twelve amino acids 480CNGVEGFNCYFP491 on RBD. 9E1 works well in Western blot on S protein and immunohistochemistry on the SARS-CoV-2 infected tissue sections. The results demonstrated that 9E1 can be used as a useful tool for pathological and functional studies of SARS-CoV-2.

11.
Invest Ophthalmol Vis Sci ; 62(10): 27, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34427624

RESUMO

Purpose: We aimed to evaluate activation of conjunctiva-associated lymphoid tissue (CALT) in patients with keratitis using in vivo confocal microscopy (IVCM) and conjunctival impression cytology (CIC). Methods: In addition to anterior segment photography and corneal fluorescein staining, IVCM revealed the palpebral conjunctiva in all subjects, and CIC and immunofluorescence staining were performed. Results: Diffuse lymphoid tissue cell density in the eyes of patients with keratitis was significantly greater compared with healthy volunteers (P < 0.001). Similar trends were found in perifollicular lymphocyte density (P < 0.001), follicular density (P = 0.029), follicular center reflection intensity (P = 0.011), and follicular area (P < 0.001). Immunofluorescence staining showed that the proportions of CD4+ (61.7% ± 8.0% vs. 17.3% ± 10.2%, respectively, P < 0.001) and CD8+ (46.9% ± 10.0% vs. 19.6% ± 11.5%, respectively, P < 0.001) cells in patients with keratitis was greater compared with healthy volunteers. Interestingly, we also observed changes in the contralateral eye in subjects with keratitis. Conclusions: Our research suggests that CALT, as an ocular immune structure, is activated and plays an important role in the pathogenesis of keratitis. This has been overlooked previously. CALT is also active in the contralateral eye of subjects with keratitis.


Assuntos
Túnica Conjuntiva/patologia , Córnea/patologia , Infecções Oculares Bacterianas/patologia , Imunidade Celular , Ceratite/patologia , Tecido Linfoide/patologia , Adulto , Túnica Conjuntiva/imunologia , Córnea/metabolismo , Infecções Oculares Bacterianas/imunologia , Infecções Oculares Bacterianas/metabolismo , Feminino , Humanos , Ceratite/imunologia , Ceratite/metabolismo , Tecido Linfoide/imunologia , Tecido Linfoide/metabolismo , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Estudos Retrospectivos
12.
Arch. endocrinol. metab. (Online) ; 65(4): 421-427, July-Aug. 2021. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1339104

RESUMO

ABSTRACT Objective: To evaluate the effect of beinaglutide on weight loss and plasma protein patterns of inflammation/obesity relevant cytokines and biomarkers. Materials and methods: This study involved 36 adult patients with a body mass index (BMI) of ≥ 24 kg/m2 and T2DM. Beinaglutide was administered for three months. Changes in body weight, fasting plasma glucose (FPG) level, 2 h postprandial plasma glucose (2h-PG) level, glycosylated hemoglobin (HbA1c) level, BMI and visceral and subcutaneous fat areas were measured at baseline and after three months of treatment. In addition, relevant inflammation/obesity cytokines and biomarkers were measured. Results: After three months, beinaglutide treatment led to significant changes, including in body weight, BMI, FPG level, HbA1c level, visceral and subcutaneous fat areas. In addition, serpin E1, leptin, C-reaction protein (CRP) and tumor necrosis factor-α (TNF-α) also decreased significantly. The plasma protein concentrations of CRP (Log2 transformed) were found to be positively correlated with the percentage of weight loss (R = 0.514 and p-value = 0.021). Conclusion: Beinaglutide treatment resulted in weight loss, plasma glucose control and anti-inflammatory effects in patients with T2DM and overweight/obesity.

13.
Arch Endocrinol Metab ; 65(4): 421-427, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34283904

RESUMO

Objective: To evaluate the effect of beinaglutide on weight loss and plasma protein patterns of inflammation/obesity relevant cytokines and biomarkers. Methods: This study involved 36 adult patients with a body mass index (BMI) of ≥ 24 kg/m2 and T2DM. Beinaglutide was administered for three months. Changes in body weight, fasting plasma glucose (FPG) level, 2 h postprandial plasma glucose (2h-PG) level, glycosylated hemoglobin (HbA1c) level, BMI and visceral and subcutaneous fat areas were measured at baseline and after three months of treatment. In addition, relevant inflammation/obesity cytokines and biomarkers were measured. Results: After three months, beinaglutide treatment led to significant changes, including in body weight, BMI, FPG level, HbA1c level, visceral and subcutaneous fat areas. In addition, serpin E1, leptin, C-reaction protein (CRP) and tumor necrosis factor-α (TNF-α) also decreased significantly. The plasma protein concentrations of CRP (Log2 transformed) were found to be positively correlated with the percentage of weight loss (R = 0.514 and p-value = 0.021). Conclusion: Beinaglutide treatment resulted in weight loss, plasma glucose control and anti-inflammatory effects in patients with T2DM and overweight/obesity.


Assuntos
Diabetes Mellitus Tipo 2 , Adulto , Glicemia , Índice de Massa Corporal , China , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Perda de Peso
14.
BMC Ophthalmol ; 21(1): 259, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34130654

RESUMO

BACKGROUND: Diabetic retinopathy is the most common microvascular complication of diabetes; however, early changes in retinal microvessels are difficult to detect clinically, and a patient's vision may have begun to deteriorate by the time a problem is identified. Optical coherence tomography angiography (OCTA) is an innovative tool for observing capillaries in vivo. The aim of this study was to analyze retinal vessel density and thickness changes in patients with diabetes. METHODS: This was a retrospective, observational cross-sectional study. Between August 2018 and February 2019, we collected OCTA data from healthy participants and diabetics from the First Affiliated Hospital of Harbin Medical University. Analyzed their retinal vessel density and thickness changes. RESULTS: A total of 97 diabetic patients with diabetes at different severity stages of diabetic retinopathy and 85 controls were involved in the experiment. Diabetic patients exhibited significantly lower retinal VD (particularly in the deep vascular complexes), thickening of the neurosensory retina, and thinning of the retinal pigment epithelium compared with controls. In the control group, nondiabetic retinopathy group and mild diabetic retinopathy group, superficial VD was significantly correlated with retinal thickness (r = 0.3886, P < 0.0001; r = 0.3276, P = 0.0019; r = 0.4614, P = 0.0024, respectively). CONCLUSIONS: Patients with diabetes exhibit ischemia of the retinal capillaries and morphologic changes in vivo prior to vision loss. Therefore, OCTA may be useful as a quantitative method for the early detection of diabetic retinopathy.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Estudos Transversais , Retinopatia Diabética/diagnóstico por imagem , Angiofluoresceinografia , Fundo de Olho , Humanos , Vasos Retinianos/diagnóstico por imagem , Estudos Retrospectivos , Tomografia de Coerência Óptica
15.
Invest Ophthalmol Vis Sci ; 62(6): 12, 2021 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-33974047

RESUMO

Purpose: The purpose of this study was to investigate the limbal changes in the palisades of Vogt (POV) in patients with herpes simplex keratitis (HSK) and herpes zoster ophthalmicus (HZO) with the application of in vivo confocal microscopy (IVCM). Methods: We enrolled 35 eyes of 35 consecutive patients with HSK and 4 patients with HZO in this observational study. Thirty-five participants were also recruited from a healthy population as the control group. All subjects were examined by IVCM in addition to routine slit-lamp biomicroscopy. The IVCM images of the corneal basal epithelial cells, corneal nerve, and the corneoscleral limbus were acquired and then were analyzed semiquantitatively. Results: The rate of absent and atypical POV was significantly higher in the affected eyes of patients with HSK than in the contralateral eyes and eyes of controls (88.57% vs. 65.71% vs. 17.14%, P < 0.01). In the HZO group, the rate of absent and atypical POV was 100% in the affected eyes and 50% in the contralateral eyes. When compared to the contralateral unaffected eyes and control eyes, the average density of the central basal epithelial cells and the sub-basal nerve plexus density and the total number of nerves in the central area of the affected eyes were significantly lower in the HSK group (1541 ± 704.4 vs. 2510 ± 746.8 vs. 3650 ± 746.1 cells/mm2, P < 0.0001). Spearman's rank correlation showed that the presence of absent and atypical POV had a significant negative correlation with central corneal basal epithelial cells (rs = -0.44979, P < 0.0001), the density of total nerves (rs = -0.49742, P < 0.0001), and the total nerve numbers (rs = -0.48437, P < 0.0001). A significant positive correlation was established between the presence of absent and atypical POV and HSK severity in affected eyes in the superior, inferior, nasal, and temporal quadrants (rs = 0.68940, rs = 0.78715, rs = 0.65591, and rs = 0.75481, respectively, P < 0.0001) and the contralateral eyes (rs = 0.51636, rs = 0.36207, rs = 0.36990, rs = 0.51241, correspondingly, P < 0.0001). Conclusions: Both eyes of patients with unilateral HSK and HZO demonstrated a profound and significant loss of limbal stem cells, which may explain the fact that HSK and HZO are risk factors for limbal stem cell deficiency (LSCD) in both eyes. The loss of LSCs was strongly correlated with the sub-basal nerve plexus and central basal epithelial cell alterations as shown by IVCM.


Assuntos
Infecções Oculares Virais/patologia , Herpes Zoster Oftálmico/patologia , Ceratite Herpética/patologia , Limbo da Córnea/patologia , Células-Tronco/patologia , Adulto , Contagem de Células , Estudos Transversais , Infecções Oculares Virais/diagnóstico por imagem , Feminino , Herpes Zoster Oftálmico/diagnóstico por imagem , Humanos , Ceratite Herpética/diagnóstico por imagem , Limbo da Córnea/diagnóstico por imagem , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Estudos Prospectivos
16.
Theranostics ; 11(13): 6607-6615, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995679

RESUMO

SARS-CoV-2 infection, which is responsible for the current COVID-19 pandemic, can cause life-threatening pneumonia, respiratory failure and even death. Characterizing SARS-CoV-2 pathogenesis in primary human target cells and tissues is crucial for developing vaccines and therapeutics. However, given the limited access to clinical samples from COVID-19 patients, there is a pressing need for in vitro/in vivo models to investigate authentic SARS-CoV-2 infection in primary human lung cells or tissues with mature structures. The present study was designed to evaluate a humanized mouse model carrying human lung xenografts for SARS-CoV-2 infection in vivo. Methods: Human fetal lung tissue surgically grafted under the dorsal skin of SCID mice were assessed for growth and development after 8 weeks. Following SARS-CoV-2 inoculation into the differentiated lung xenografts, viral replication, cell-type tropism and histopathology of SARS-CoV-2 infection, and local cytokine/chemokine expression were determined over a 6-day period. The effect of IFN-α treatment against SARS-CoV-2 infection was tested in the lung xenografts. Results: Human lung xenografts expanded and developed mature structures closely resembling normal human lung. SARS-CoV-2 replicated and spread efficiently in the lung xenografts with the epithelial cells as the main target, caused severe lung damage, and induced a robust pro-inflammatory response. IFN-α treatment effectively inhibited SARS-CoV-2 replication in the lung xenografts. Conclusions: These data support the human lung xenograft mouse model as a useful and biological relevant tool that should facilitate studies on the pathogenesis of SARS-CoV-2 lung infection and the evaluation of potential antiviral therapies.


Assuntos
COVID-19/imunologia , Modelos Animais de Doenças , Pulmão/patologia , Mucosa Respiratória/citologia , SARS-CoV-2/imunologia , Feto Abortado , Animais , COVID-19/patologia , COVID-19/virologia , Células Cultivadas , Células Epiteliais/virologia , Xenoenxertos , Humanos , Pulmão/imunologia , Pulmão/virologia , Transplante de Pulmão , Masculino , Camundongos , Camundongos SCID , Cultura Primária de Células , SARS-CoV-2/patogenicidade , Replicação Viral
17.
PeerJ ; 9: e11350, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34026352

RESUMO

Background: Gliomas are the most common primary tumors of the central nervous system. The complexity and heterogeneity of the tumor makes it difficult to obtain good biomarkers for drug development. In this study, through The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA), we analyze the common diagnostic and prognostic moleculer markers in Caucasian and Asian populations, which can be used as drug targets in the future. Methods: The RNA-seq data from Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) were analyzed to identify signatures. Based on the signatures, the prognosis index (PI) of every patient was constructed to predict the prognostic risk. Also, gene ontology (GO) functional enrichment analysis and KEGG analysis were conducted to investigate the biological functions of these mRNAs. Glioma patients' data in the CGGA database were introduced to validate the effectiveness of the signatures among Chinese populations. Excluding the previously reported prognostic markers of gliomas from this study, the expression of HSPA5 and MTPN were examined by qRT-PCR and immunohistochemical assay. Results: In total, 20 mRNAs were finally selected to build PI for patients from TCGA, including 16 high-risk genes and four low-risk genes. For Chinese patients, the log-rank test p values of PI were both less than 0.0001 in two independent datasets. And the AUCs were 0.831 and 0.907 for 3 years of two datasets, respectively. Moreover, among these 20 mRNAs, 10 and 15 mRNAs also had a significant predictive effect via univariate COX analysis in CGGA_693 and CGGA_325, respectively. qRT-PCR and Immunohistochemistry assay indicated that HSPA5 and MTPN over-expressed in Glioma samples compared to normal samples. Conclusion: The 20-gene signature can forecast the risk of Glioma in TCGA effectively, moreover it can also predict the risks of Chinese patients through validation in the CGGA database. HSPA5 and MTPN are possible biomarkers of gliomas suitable for all populations to improve the prognosis of these patients.

18.
J Biomed Nanotechnol ; 17(3): 426-438, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33875077

RESUMO

Ovarian cancer has been the most lethal gynaecological malignancy worldwide. Additionally, triptolide is an active substance that has been extracted from the Chinese herbal medicine T. wilfordii Hook F. , which possesses anti-tumor, immunomodulatory and anti-inflammatory properties. In recent years, TP has attracted increasing attention because of its broad-spectrum efficient anti-tumor activity. Nevertheless, its clinical utility is limited due to its severe side effects. In this study, we constructed an exosome-encapsulated TP targeted drug delivery systems, studying its anti-tumor effects and mechanisms in vivo and in vitro . We observed that compared with free TP, TP-Exos significantly enhanced anti-ovarian cancer effects and reduce toxicity to important organs. We further demonstrated that TP-Exos induced apoptosis of ovarian cancer cells, regulated tumor immunity by activating the mitochondrial apoptosis pathway and selectively inhibited M2 tumor-associated macrophages and their tumor-promoting mediators in the tumor microenvironment. In summary, TP-Exos are a promising treatment for ovarian cancer.


Assuntos
Diterpenos , Exossomos , Neoplasias Ovarianas , Fenantrenos , Apoptose , Compostos de Epóxi , Feminino , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Microambiente Tumoral
19.
Acta Ophthalmol ; 99(8): 909-915, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33565253

RESUMO

PURPOSE: Understanding the spectrum of ocular pathogens in a given geographic region is important for devising appropriate practical treatment. Therefore, we examined the pathogen spectrum and antibiotic resistance of microbial keratitis in northeast China. METHODS: In this retrospective observational study, we reviewed the microbiology laboratory records of patients diagnosed with microbial keratitis in a tertiary eye hospital in Harbin, northeast China, between 2017 and 2019, and analysed the pathogen spectrum and antibiotic susceptibility. RESULTS: We collected 462 specimens, of which 282 exhibited positive cultures. Among these cultures, 257 were bacterial and 25 were fungal. Of the 257 bacterial isolates, 214 (83.27%) were gram positive whereas 43 (16.73%) were gram negative. The most prevalent gram-positive pathogen was coagulase-negative staphylococcus (CoNS; 58.37%), followed by Staphylococcus aureus (S. aureus; 20.62%) and Streptococcus pneumoniae (2.33%). Of the gram-negative bacterial isolates, 10 were Pseudomonas aeruginosa (3.89%). The most frequently detected ocular pathogens from fungal isolates were Fusarium species (40%). We also found more culture-positive cases of bacterial keratitis in summer. Overall, 16.98% S. aureus and 64.00% CoNS isolates were methicillin resistant. These methicillin-resistant bacteria were also more likely to be resistant to other antibiotics, with multidrug resistance found in 77.78% methicillin-resistant S. aureus and 90.63% methicillin-resistant CoNS. However, all gram-positive isolates were sensitive to vancomycin and linezolid. CONCLUSION: Coagulase-negative staphylococcus are the most common ocular pathogens in northeast China. We also show the prevalence of methicillin resistance and concurrent multidrug resistance among staphylococcal isolates. Monitoring the patterns of antimicrobial resistance could help in the management selection.

20.
J Biomed Inform ; 116: 103721, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33631382

RESUMO

A phenomenon called White Coat Hypertension (WCH) often occurs when measuring blood pressure (BP) in a real medical environment. Utilizing virtual reality (VR) technology to present appropriate relaxation scenes can isolate the real medical environments and may provide a new method to avoid WCH and improve the accuracy of BP measurement. In this study, we designed four immersive VR relaxation scenes and conducted an experiment to explore the role of VR scenes in eliminating/detecting WCH in BP measurement. Results from the current sample showed that both systolic BP and diastolic BP measured in the simulated medical environment were significantly higher than the baseline level and the VR scene condition, while there were no significant differences between the BPs measured in VR scenes and the baseline level. It can be concluded that VR provides an effective approach to avoid WCH in BP measurement by visually and aurally isolating the real environment and assisting relaxation and provides a new approach to detect the occurrence of WCH by the comparison of BPs measured in the VR scene condition and real medical environments.


Assuntos
Hipertensão , Realidade Virtual , Hipertensão do Jaleco Branco , Pressão Sanguínea , Determinação da Pressão Arterial , Humanos , Hipertensão/diagnóstico , Hipertensão do Jaleco Branco/diagnóstico
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