Background: Benzothiazole and its derivatives have been extensive studied due to their versatile biological properties and pharmaceutical applications. We recently found that the BMP326 (1-(1,3-benzothiazol-2-yl)-3-(2-methoxyphenyl)-1H-pyrazol-5-ol), a novel benzothiazole derivative, have anti-inflammatory properties in lipopolysaccharide(LPS)-induced RAW264.7 macrophages and there were no relevant reports previously. Methods and Results: Treatment with BMP326(5, 10 and 20 μM) can significantly inhibit nitric oxide production and down-regulate mRNA expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) but did not cause significant cytotoxicity on RAW264.7 macrophages. It is also observed BMP326 can inhibit LPS-stimulated interleukin (IL)-6, interleukin(IL)-1β, tumor necrosis factor (TNF)-α production depending on its dosage. The gene transcription levels of IL-6, IL-1β and TNF-α were reduced under BMP326 exposure in LPS-treated RAW264.7 cells. In addition, we explored the inhibitory mechanisms of BMP326 on the production of pro-inflammatory mediators. The results showed that BMP326 inhibited nuclear factor kappa B (NF-κB) activation by reducing the phosphorylation of p65 and IκBα. Moreover, the phosphorylation of p38 MAPK (p38), extracellular signal-regulated kinases 1/2 (ERK1/2), and c-Jun N-terminal kinase (JNK) in RAW264.7 cells which are stimulated with LPS were suppressed in a dose-dependent manner. Conclusions: In summary, these results suggest that BMP326 exerts anti-inflammatory properties via suppression of the NF-κB and MAPKs signaling pathways.

Background: Peripheral blood-derived natural killer (NK) cells spontaneously lyse tumor cells without prior sensitization. However, NK cells in peripheral blood (PBNK cells) are in a resting state and exhibit inhibitory phenotypes and impaired cytotoxicity. Thus, strengthening the cytotoxic effector function of PBNK cells and improving NK cell expansion in vitro for a convenient allogeneic therapy are essential. Materials and Methods: Pure cytokine activation and expansion of NK cells [super NK (SNK)] from peripheral blood mononuclear cells were studied. Markers of activated and inhibited NK cells and cytokine secretion by NK cells were examined using flow cytometry. NK cell antitumor activity in vitro was assessed using lactate dehydrogenase (LDH) cytotoxicity assay and an Incucyte real-time imaging system. Additionally, the function of SNK cells against ascites caused by ovarian cancer in NOD-Prkdc(em26Cd52)il2rg(em26Cd22)/Nju (NCG) mice were determined. In a further investigation of the differences between PBNK and SNK, the mRNA of both cells was sequenced and analyzed. Results: Human peripheral blood mononuclear cells showed selective NK cell expansion upon cytokine activation and culture. Both SNK and PBNK cells expressed activation markers, but at different levels, and SNK cells secreted more cytokines related to cytotoxicity than PBNK cells did. Accordingly, SNK cells exhibited strong antitumor activity ex vivo and improved NCG mice survival after intraperitoneal ovarian cancer transplantation. Mechanistically, SNK cells expressed more genes associated with nucleotide metabolism, fatty acid, and ATP metabolism than PBNK cells. Conclusion: SNK cells derived from peripheral blood mononuclear cells have sufficiently activated mature characteristics and high antitumor activity, rendering them a highly promising and essential therapeutic approach for cancer treatment. KEYWORDS Natural killer cell; Peripheral blood; Ovarian cancer; Ascites

The gut microbiota significantly impacts antitumour immunity and alters the effectiveness of cancer immunotherapy. Immunotherapies, notably inhibitors of immune checkpoints that target programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)， have profoundly changed the way advanced and metastatic cancer is treated and dramatically improved overall and progression-free survival. However, the underlying molecular mechanisms by which the gut microbiota affects antitumour immunity and the efficacy of cancer immunotherapy remain elusive. In this review, we summarize the latest knowledge supporting the associations among the gut microbiota, antitumour immunity, and immunotherapy. The potential molecular mechanisms underlying these associations are explained in terms of four aspects.

Objective To report a case of Granulomatosis with Polyangiitis (GPA)with Diffuse alveolar hemorrhage(DAH)that developed following Coronavirus disease 2019 (COVID-19) in an adolescent boy, and perform a literature review to better understand this disorder.Methods Retrospectively analyze the data of a case of GPA following COVID-19 infection, to summarize the clinical characteristics of GPA following COVID-19 infection by searching the database (PubMed,Wanfang Data,CNKI) and comprehensively analyze the literature results. Results 9 cases were reported，combined with our case，there were 10 cases of GPA following COVID-19 infection,including 4 males and 6 females,with an average age of(40.6±18.6)years,and the time interval between COVID-19 and diagnosis of GPA ranged from 1 day to 3 months for all 10 cases. The rate of mortality was 10.0%(1/10).Commonly seen clinical manifestations were cough(70.0%),dyspnea(50.0%),and Arthralgia/Myalgia(40.0%). CT scans showed ground-glass opacities，multifocal pulmonary nodules.Of all these patients, c-ANCA and PR3-antibody positivity were found .Conclusion COVID-19 pneumonia and COVID-19- induced new-onset GPA share many clinical and radiological features, making it challenging for clinicians to distinguish between the two. Our study also provided some clues about the diagnostic challenge of GPA induced by COVID-19.

Introduction: Children with atopic dermatitis(AD) suffer from a high illness burden that has a detrimental influence on their quality of life . Objective: To determine whether topical corticosteroids and dupilumab are effective for treating atopic dermatitis in children. Methods: Web of Science, PubMed, and Embase, three well-known databases, were used to conduct a thorough literature search. Using a fixed-effects or random-effects model, the standard mean difference (SMD) or risk ratios (RR) with 95% confidence interval (CI) were calculated.PROSPERO lists the trial protocol as CRD42023408546. Results: There were 3 investigations in total, and 896 people met the requirements for inclusion.The combined estimate showed that dupilumab plus topical corticosteroids had numerically greater efficacy in terms of EASI-50, EASI-75, EASI-90, and Investigator Global Assessment (IGA) score of 0 or 1.When compared to placebo, children who got topical corticosteroids and dupilumab scored considerably higher on the dermatological life quality index (CDLQI). The number of individuals who achieved IGA0/1 rose with the use of dupilumab and topical corticosteroids. Conclusions:In children with AD, dipilumab and topical corticosteroids may be used to treat the symptoms. Given the substantial variation between the research, the findings should, however, be regarded with caution.

A document by Zhengjiang Wang. Click on the document to view its contents.

Background: Allergic rhinitis is the specific inflammation against allergen by immune defense cells on nasal mucosa, which can lead to chronic nasal symptoms such as sneezing, itching, runny nose, and nasal congestion. it is associated with high morbidities including sinusitis, asthma, otitis media, hypertrophied inferior turbinate and nasal polyp. Despite its complications, it remains poorly recognized and tracked. Methods: A cross-sectional hospital based study was done, a total of 221 patients received ORL services at Kilimanjaro Christian medical Centre during study period were interviewed all patients with a clinical diagnosis of allergic rhinitis were captured; Data was collected using a pre-tested coded questionnaire (SFAR) The data was then analyzed by SPSS version 22. Results: A total of 221 patients with clinical diagnosis of allergic rhinitis were approached in Six (6) months study period, 111 (50.2%) were females, 140 (63.4%) were residing in urban areas. The prevalence of allergic rhinitis was 23.9%. Factors such as age OR 0.12, 95% C.I (0.03; 0.40), education OR 0.13, 95% C.I (0.04; 0.44), occupation OR 3.75, 95% C.I (1.36; 10.32), Adenotonsillar hypertrophy OR 4.66, 95% C.I (2.21; 9.80) and OME OR 4.11, 95% C.I (1.32; 12.83) (p=0.009) was found to be significantly associated with allergic rhinitis. 60.4%, Inferior turbinate hypertrophy was the leading co-morbidity of allergic rhinitis which accounts 64.7%. Conclusion: Allergic rhinitis is among the common health problems affecting Tanzanians. It is a commonly seen disorder in younger age (<15 yrs) which is in correlation with other studies done in Africa and worldwide.

Objective：To compare the efficacy and safety of telbivudine (LdT), tenofovir alafenamide fumarate (TAF) and tenofovir disoproxil fumarate (TDF) for preventing Hepatitis B transmission in immune-tolerant pregnant women with HBV infection. Methods: We conducted a retrospective cohort study involving women who had HBV DNA 2 × 105 IU / ml and initiated LdT, TDF or TAF to prevent mother-to-child transmission (MTCT). The primary endpoint was the safety of mothers and infants. The secondary endpoints were maternal hepatitis B virus DNA reduction at delivery and mother-to-child transmission rate. Results: A total of 96 patients were enrolled in the study ( LdT group, n=36; TDF group, n=35; TAF group, n=25). All infants received hepatitis B virus immunoprophylaxis. The mother-to-child transmission rate was 0%( [0 of 25] vs. [0 of 35] vs [0 of 36], P＞0.05). No severe liver function damage occurred in any of the mothers. Babies delivered in all groups had prenatal ultrasound screening abnormalities, but abnormality rates were not statistically significant between groups. Conclusion: The application of TDF, TAF, or LdT to immune-tolerant HBV-infected pregnant women in middle-late pregnancy, can successfully interrupt mother-to-child transmission of the HBV virus. However, for all three groups of pregnant women who delivered babies with abnormal prenatal ultrasound screening, an expanded sample size may be needed for further observation.

Alzheimer’s disease (AD) is a neurological condition that is significantly more prevalent when people become older. It may start out early or late. A rise in levels of proinflammatory cytokines and microglial activation, both of which contribute to the central nervous system’s inflammatory state, are characteristics of AD (CNS). As opposed to this, periodontitis is a widespread oral infection brought on by gram-negative anaerobic bacteria. By releasing proinflammatory cytokines into the systemic circulation, periodontitis can be classified as a “low-grade systemic disease.” Periodontitis and AD are linked by inflammation, which is recognized to play a crucial influence in both the illness and treatment process. The current review sought to highlight the effects of pro-inflammatory cytokines, which are released during periodontal and Alzheimer’s diseases in the pathophysiology of both conditions. It also addresses the puzzling relationship between AD and periodontitis, highlighting the etiology, and potential ramifications.

Background: The efficacy of immunization against an airborne pathogen depends in part on its ability to induce antibodies at the major entry site of the virus, the mucosa. Recent studies have revealed that mucosal immunity is poorly activated after vaccination with mRNA vaccines, thus failing in blocking virus acquisition upon its site of initial exposure. Little information is available about the induction of mucosal immunity by inactivated and recombinant COVID-19 vaccines. This study aims to investigate this topic. Methods: Saliva and plasma samples from 440 healthy Congolese were collected including (1) fully vaccinated two month post vaccination with either an inactivated or a recombinant COVID-19 vaccine and (2) non-vaccinated control group. Total anti-SARS-COV-2 RBD IgG and IgA antibodies were assessed using in-house ELISAs for both specimens. Findings: Altogether, the positivity of IgG was significantly higher in plasma than in saliva samples both in vaccinated and non-vaccinated control groups. Inversely, IgA positivity was slightly higher in saliva than in plasma of vaccinated group. The overall IgG and IgA levels were respectively over 103 and 14 times lower in saliva than in plasma samples. We found a strong positive correlation between IgG in saliva and plasma also between IgA in both specimens (r = 0.70 for IgG and r = 052 for IgA). Interestingly, contrary to IgG, the level of salivary IgA was not different between seropositive control group and seropositive vaccinated group. No significant difference was observed between recombinant and Inactivated COVID-19 vaccines in total IgG and IgA antibody concentration release 2 months post vaccination both in plasma and saliva. Conclusion: Inactivated and recombinant COVID-19 vaccines in use in the Republic of Congo poorly activated mucosal IgA mediated antibody response two months post-vaccination.

Purpose: Myeloperoxidase(MPO) has been found to be the mediator in various inflammatory diseases. Bacterial infection of the intestine and hypoxia can both lead to inflammatory responses, but the effects of MPO in these phenomena are still unclear. Methods: By building the MPO-/- mice ，we examined relevant inflammatory factors and tissue damage in mice with intestinal Citrobacter rodentium infection and hypoxia. The body weight and excreted microorganisms were monitored. Intestinal tissues were collected 7 days after bacterial infection under hypoxia to undergo HE staining and assess the degree of pathological damage. The levels of TNF-α, IFN-γ, IL-6 and IL-1β inflammatory factors in the serum were quantified using ELISA. PCR, WB and IF assays to determine the expression of chemokines MCP1, MIP2 and KC in the colon and spleen. . Results: Citrobacter rodentium infection and hypoxia caused weight loss , intestinal colitis and splenic inflammatory cells active proliferation in wild type mice and this phenomena was alleviative in MPO-/- mice. Also，the capability of clearing bacteria in MPO-/- mice significantly declined. The level of TNF-α in the serum and spleen was both lower in MPO-/- hypoxia C. rodentium-infected mice than that in wild type mice. The chemokines expression levels of MIP2, KC and MCP1 in the spleen and colon of each bacterial infected group were significantly increased (P<0.05), while in hypoxia, the factors in the spleen and colon were decreased (P<0.05). Meanwhile, The levels of these chemokines in the MPO-/- mice were found to be lower than those observed in the wild type mice. Conclusion: MPO plays an important role of the inflammatory responses in infectious enteritis and hypoxia in mice. Loss of MPO may greatly reduces the body’s inflammatory responses to fight deseases.

Splicing factor proline- and glutamine-rich (SFPQ) can interact with RNAs to regulate gene expression. The function of SFPQ in the immunotherapy of non-small cell lung cancer (NSCLC) is investigated in this study. H1299 and A549 cells were transfected with shSFPQ plasmid. Cell counting kit-8 (CCK-8) and cell clone formation were utilized to detect survival and proliferation. Programmed death-ligand 1 (PD-L1) and SFPQ were detected in NSCLC patients treated with anti-PD-L1 antibody. Dual-luciferase assays, RNA immunoblotting, RNA pull-down, and mRNA stability assay were applied to verify the regulation of PD-L1 with SFPQ. Human peripheral blood mononuclear cells (PBMC)-derived dendritic cells were loaded with irradiated A549 and H1299 cells, which were cultured with autologous CD8+T cells and tumor cells to perform in vitro tumor-specific cytotoxic T cells (CTL) cytotoxicity analysis. SFPQ silencing inhibited the survival and proliferation of H1299 and A549 cells with down-regulated PD-L1 expression. PD-L1 and SFPQ expression were markedly higher in anti-PD-L1 antibody treatment responders compared to non-responders, which showed a positive Pearson correlation (r=0.76, p<0.001). SFPQ up-regulated the relative mRNA and protein expression of PD-L1 by binding to the PD-L1 3’UTR to slow the decay of PD-L1 mRNA. SFPQ silencing promoted the killing effect of CTL on A549 and H1299 cells. SFQP up-regulates PD-L1 expression by binding with PD-L1 3’UTR to slow the decay of PD-L1 mRNA, and SFQP silencing promotes CTL mediated cytotoxicity on NSCLC cells.

Indeterminate cell histiocytosis (ICH) is a rare histiocytic proliferative disease with unknown etigo, which shared immunophenotypic features of Langerhans cell and macrophages. ICH cells express CD1a, S-100, and CD68 whereas langerin (CD207) is negative. This study presents a case of a 75 -year-old man with varying sizes of some scattered annular erythema over his chest, abdomen, limbs and 4 bullous on the thigh for 1.5months. He had about 9 month’s history of esophageal cancer and treated with the radical radiotherapy treatment. Histopathologic examination of his abdomen demonstrated accumulation of mononuclear cells in the epidermis, infiltration of eosinophils and lymphocytes in the dermal superficial layer. The histology of the blister reported the formation of old subepidermal blister, slurry and eosinophils in the blister as well as infiltration of eosinophils and lymphocytes in the dermal superficial layer. Results of immunohistochemistry identified positive for CD1a, S-100 and CD68 in epidermal cells and dermal cells aggregation but negative for CD207. However, the blisters and bullous were found over the lower limbs after 38 days. A diagnosis of bullous pemphigoid (BP) was arrived at according to the examination of histopathology and direct immunofluorescent. Therefore, that esophageal carcinoma, ICH, and BP lied in a single patient, was found to be a rare case that deserved our considering of the possible mechanism.

Abstract: Background: The abnormal expression of lncRNA HOTAIR has been associated with synovial angiogenesis in rheumatoid arthritis (RA). The aim of this study is to investigate whether lncRNA HOTAIR can participate in synovial angiogenesis in RA by regulating the PI3K/AKT pathway through the miR-126/PIK3R2 axis. Methods: In this study, we conducted in vitro experiments by designing overexpression plasmids and small interfering RNAs targeting lncRNA HOTAIR and then transfected them into fibroblast-like synoviocytes (FLS) obtained from RA patients. We then co-cultured the modified FLS with human umbilical vein endothelial cells (HUVEC) to establish an RA-FLS-induced HUVEC model. We investigated the effects of lncRNA HOTAIR on the proliferation, migration, and tube formation abilities of HUVECs, as well as the expression of synovial endothelial cell markers, angiogenic factors, and the PI3K/AKT pathway. To validate the interactions between lncRNA HOTAIR, miR-126-3p, and PIK3R2, we used bioinformatics and luciferase reporter experiments. We also used a combination of real-time fluorescence quantitative (RT-qPCR), Western blotting (WB), and immunofluorescence (IF) methods to identify target genes and proteins. Results: LncRNA HOTAIR was highly expressed in HUVEC cells induced by RA-FLS. Overexpression of lncRNA HOTAIR significantly increased the expression of VEGF, bFGF, CD34 and CD105 in HUVEC cells, promoted their proliferation, invasion, and tube formation, while the silencing of lncRNA HOTAIR reversed these effects, and the PI3K/AKT activator also reversed them. Overexpression of lncRNA HOTAIR activated the PI3K/AKT pathway, promoting the expression of PI3K, AKT, and P-AKT proteins. Bioinformatics and dual-luciferase assays verified the targeting relationship between LncRNA HOTAIR, miR-126-3p, and PIK3R2. Conclusion: LncRNA HOTAIR can activate the PI3K/AKT pathway, possibly through the regulatory axis of miR-126-3p/PIK3R2, and thus participate in synovial angiogenesis in rheumatoid arthritis.

Background: Luteolin is a natural flavonoid, and its neuroprotective and anti-inflammatory effects have been confirmed to mitigate neurodegeneration. Despite these findings, the underlying mechanisms responsible for these effects remain unclear. Toll-like receptor 4 (TLR4) is widely expressed in microglia and plays a pivotal role in neuroinflammation and neurodegeneration. Here we outline studies aimed at determining the mechanisms responsible for the neuroprotective and anti-inflammatory effects of luteolin using a mouse model of Parkinson’s disease (PD), and specifically focusing on the role of TLR4 in this process. Methods: The mouse model of PD used in this study was established through a single injection of LPS. Mice were subsequently randomly assigned to either the luteolin or vehicle-treated group, then motor performance and dopaminergic neuronal injury were evaluated. BV2 microglial cells were treated with luteolin or vehicle saline prior to LPS challenge. mRNA expression of microglial marker IBA-1 and M1/M2 polarization markers, as well as the levels of pro-inflammatory cytokines in the mesencephalic tissue and BV2 were quantified by RT-PCR and ELISA, respectively. Apoptosis and cell viability of SH-SY5Y cells co-cultured with BV2 were examined. TLR4 RNA transcript and protein abundance in mesencephalic tissue and BV2 cells were detected. NFkB p65 subunit phosphorylation both in vivo and in vitro was evaluated by immunoblotting. Results: Luteolin treatment induced functional improvements and alleviated dopaminergic neuronal loss in our PD model. Luteolin inhibited apoptosis and promoted cell survival in SH-SY5Y cells. Luteolin treatment shifted microglial M1/M2 polarization towards the anti-inflammatory M2 phenotype both in vivo and in vitro. Finally, we found that luteolin treatment significantly downregulated both TLR4 mRNA and protein expression as well as restraining NFkB p65 subunit phosphorylation. Conclusions: Luteolin promoted dopaminergic neuronal survival in vivo and in vitro by blocking TLR4-mediated neuroinflammation.

Non-coding RNAs are a group of RNAs that cannot synthesize proteins, but are critical in the regulation of gene expression. A growing number of studies discovered that miRNAs and lncRNAs, as the two major members of the ncRNA family, play vital roles in regulating the physiological and pathological processes of lung diseases, such as pneumonia, COPD (chronic obstructive pulmonary disease), lung cancer, and asthma. These interactions are intricately linked to the the regulation of immune response, cell proliferation and apoptosis, cell differentiation and polarization, cytokine secretion, or acts as tumor suppressors or promoters. Understanding the role of ncRNAs in lung diseases might provide novel insights into disease mechanisms and potential therapeutic targets. In this review, we will go over the fundamental characteristics and functions of miRNAs and lncRNAs, their potential interaction mechanisms, then summarize the newly explorations on the role of these interactions between lncRNAs and miRNAs in various lung diseases.

Varicella Zoster is a neurotropic virus which leads to acute varicella or it may lay dormant in the spinal root ganglion. Reactivation of varicella zoster causes Herpes Zoster (HZ) and occurs commonly in immunosuppressed conditions like COPD. Severity of Herpes Zoster is also higher among those with comorbidities like COPD. Even among COPD patients, the severity of HZ is said to be higher among those using oral corticosteroids than those using inhaled steroids due to greater immunosuppressive effect. It has also been found that incidence rate of COPD exacerbations, transient ischemic attack and stroke are higher among COPD patients with HZ compared to those without HZ. Herpes zoster vaccinations prevent reactivation of latent HZ and reduce the associated complications. Live attenuated and recombinant vaccines are available for vaccination among which recombinant vaccine is found to be more effective. The cost burden due to HZ among COPD patients was also higher compared to those without HZ. Childhood varicella vaccination is cost effective, however cost effectiveness of adolescent vaccination is unclear.

Introduction; MS is an inflammatory progressive disease with destruction of myelin sheath of neurons and axons. Among environmental risk factors HHV-6 might plays a role in MS. HHV-6 is a lymphotropic virus causing neurological symptoms. HHV-6 may exist in the PBMCs and CNS in a latent state. Materials and Methods; This case-control study was conducted on 116 new cases of MS whom naive to MS drugs. The control group consist 116 non-MS individuals whose gender, age and their place of residency were matched with the cases. Ten ml of peripheral blood was collected from each participant, their Sera and PBMCs were separated and the DNA was extracted from them separately. After Nested-PCR, the PCR products were sequenced. Statistical analysis of data was performed by V.22 of SPSS software and chi-square and Fisher’s exact tests and Odd‘s ratio were used. The P≤0.05 was considered as statistically significant. Results; considering of existence of HHV-6, there was a significant difference in PBMCs and Sera of case and control group, but among male participants the difference between cases and controls was not significant while this figure for female participants was significant in PBMCs and Sera. Regarding age group, only 21-25 and 31-35 groups were statistically significant. All positive samples were variant 6B of HHV-6. Discussion; HHV-6 can be considered as a MS risk factor mainly in female cases, especially in the age group of 20-35. HHV-6 is in its active state (Sera) in these patients.