Mesenteric adipose tissue B lymphocytes promote intestinal injury in severe acute pancreatitis by mediating enteric pyroptosis

Background:Visceral adipose tissue(VAT)has been linked to the severe acute pancreatitis(SAP)prognosis,although the underlying mechanism remains unclear.It has been reported that pyroptosis worsens SAP.The present study aimed to verify whether mesenteric adipose tissue(MAT,a component of VAT)can cause secondary intestinal injury through the pyroptotic pathway.Methods:Thirty-six male Sprague Dawley(SD)rats were divided into six different groups.Twelve rats were randomly divided into the SAP and control groups.We monitored the changes of MAT and B lymphocytes infiltration in MAT of SAP rats.Twelve SAP rats were injected with MAT B lymphocytes or phosphate buffer solution(PBS).The remaining twelve SAP rats were first injected with MAT B lymphocytes,and then with MCC950(NLRP3 inhibitor)or PBS.We collected blood and tissue samples from pancreas,gut and MAT for analysis.Results:Compared to the control rats,the SAP group showed inflammation in MAT,including higher expression of tumor necrosis factor(TNF-α)and interleukin-6(IL-6),lower expression of IL-10,and histological changes.Flow cytometry analysis revealed B lymphocytes infiltration in MAT but not T lymphocytes and macrophages.The SAP rats also exhibited intestinal injury,characterized by lower expression of zonula occludens-1(ZO-1)and occludin,higher levels of lipopolysaccharide and diamine oxidase,and pathological changes.The expression of NLRP3 and n-GSDMD,which are responsible for pyroptosis,was increased in the intestine of SAP rats.The injection of MAT B lymphocytes into SAP rats exacerbated the inflammation in MAT.The upregulation of pyroptosis reduced tight junction in the intestine,which contributed to the SAP progression,including higher inflammatory indicators and worse histological changes.The administration of MCC950 to SAP+MAT B rats downregulated pyroptosis,which subsequently improved the intestinal barrier and ameliorated inflammatory response of SAP.Conclusions:In SAP,MAT B lymphocytes aggravated local inflammation,and promoted the injury to the intestine through the enteric pyroptotic pathway.

Hepatitis C virus in human B lymphocytes transformed by Epstein-Barr virus in vitro by in situ reverse transcriptase-polymerase chain reaction

AIM: To study persistence and replication of hepatitis C virus (HCV) in patients' peripheral blood mononuclear cells (PBMC) cultured in vitro. METHODS: Epstein Barr virus (EBV) was used to transform the hepatitis C virus from a HCV positive patient to permanent lymphoblastoid cell lines (LCL). Positive and negative HCV RNA strands of the cultured cells and growth media were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) each month. Core and NS5 proteins of HCV were further tested using immunohistochemical SP method and in situ RT-PCR. RESULTS: HCV RNA positive strands were consistently detected the cultured cells for one year. The negative-strand RNA in LCL cells and the positive-strand RNA in supernatants were observed intermittently. Immunohistochemical results medicated expression of HCV NS3 and C proteins in LCL cytoplasm mostly. The positive signal of PCR product was dark blue and mainly localized to the LCL cytoplasm. The RT-PCR signal was eliminated by overnight RNase digestion but not DNase digestion. CONCLUSION: HCV may exist and remain functional in a cultured cell line for a long period.

Bystanders or not?Microglia and lymphocytes in aging and stroke

As the average age of the world population increases,more people will face debilitating aging-associated conditions,including dementia and stroke.Not only does the incidence of these conditions increase with age,but the recovery afterward is often worse in older patients.Researchers and health professionals must unveil and understand the factors behind age-associated diseases to develop a therapy for older patients.Aging causes profound changes in the immune system including the activation of microglia in the brain.Activated microglia promote T lymphocyte transmigration leading to an increase in neuroinflammation,white matter damage,and cognitive impairment in both older humans and rodents.The presence of T and B lymphocytes is observed in the aged brain and correlates with worse stroke outcomes.Preclinical strategies in stroke target either microglia or the lymphocytes or the communications between them to promote functional recovery in aged subjects.In this review,we examine the role of the microglia and T and B lymphocytes in aging and how they contribute to cognitive impairment.Additionally,we provide an important update on the contribution of these cells and their interactions in preclinical aged stroke.

Impact of oxaliplatin and trastuzumab combination therapy on tumor markers and T lymphocyte subsets for advanced gastric cancer

BACKGROUND Advanced gastric cancer(AGC)remains a challenging malignancy with poor prognosis.The combination of oxaliplatin and trastuzumab has shown promising results in AGC treatment.This study aimed to investigate the effects of oxaliplatin and trastuzumab combination therapy on serum tumor markers and T lymphocyte subsets in patients with AGC and to explore their potential as predictive biomarkers for treatment response.AIM To investigate the impact of oxaliplatin and trastuzumab combination therapy on serum markers and T cell subsets in patients with AGC.METHODS This prospective study enrolled 60 patients with AGC.All patients received oxaliplatin(130 mg/m^(2),every 3 weeks)and trastuzumab(8 mg/kg loading dose,followed by 6 mg/kg every 3 weeks)for six cycles.Serum carcinoembryonic antigen(CEA),cancer antigen 19-9(CA19-9),and cancer antigen 72-4(CA72-4)were measured before and after treatment.T-lymphocyte subsets,including CD3+,CD4+,CD8+,and CD4+/CD8+ratios,were also evaluated.The clinical response was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1.RESULTS After six cycles of treatment,the CEA,CA19-9,and CA72-4 serum levels significantly decreased compared to baseline levels(P<0.001).The percentages of CD3+and CD4+T lymphocytes increased significantly(P<0.05),whereas the percentage of CD8+T lymphocytes decreased(P<0.05).The CD4+/CD8+ratio also significantly increased after treatment(P<0.05).Patients with a higher decrease in serum tumor markers(≥50%reduction)and a higher increase in CD4+/CD8+ratio(≥1.5-fold)showed better clinical response rates(P<0.05).CONCLUSION Oxaliplatin and trastuzumab combination therapy effectively reduced serum tumor marker levels and modulated T lymphocyte subsets in patients with AGC.Combination therapy not only has a direct antitumor effect,but also enhances the immune response in patients with AGC.Serum tumor markers and T lymphocyte subsets may serve as potential predictive biomarkers for treatment response in patients with AGC receiving combination therapy.

ROLE OF B LYMPHOCYTE AND ITS SUBPOPULATIONS IN PATHOGENESIS OF IMMUNORELATED PANCYTOPENIA

Objective To measure the quantities and apoptosis-related protein levels of B lymphocyte in the patients with immunorelated pancytopenia （IRP） and explore the action of B lymphocyte in the pathogenic mechanism of IRP. Methods Quantifies of whole B lymphocytes and CD5^＋ B lymphocytes as well as the expressions of Fas and Bcl-2 in B lymphocytes in 35 patients with untreated IRP, 15 IRP patients in complete remission （CR）, and 10 normal controls were assayed by flow cytometry. The percentages of B lymphocyte and CD5^＋ B lymphocyte were significantly higher in untreated IRP patients than in CR IRP patients and normal controls （ P 〈 0. 05 ）, and there was no significant difference between the latter two groups （ P 〉 0. 05 ）. There was no significant difference of Fas expression in B lymphocyte among three groups （ P 〉 0. 05）. The expression of Bcl-2 in B lymphocyte was significantly higher in untreated patients than in CR patients or normal controls （ P 〈 0. 01 ）, and significantly higher in CR patients than in normal controls （ P 〈 0. 01 ）. The apoptosis. related index was significantly lower in untreated patients than in CR patients or normal controls （ P 〈 0. 05 ）, and signif. icantly lower in CR patients than in normal controls （ P 〈 0. 05 ）. The percentage of B lymphocyte was positively correlated with post-treated response time （ r = 0. 53, P 〈 0. 01 ）. Conclusion The production of auto-antibodies in IRP patients probably has some relationship with the abnormal quantifies of B lymphocyte and its subpopulations as well as with the inhibition of B lymphocyte apoptosis.

Guben Tongluo Formula Protects LPS-induced Damage in Lamina Propria B Lymphocytes Through TLR4/MyD88/NF-κB Pathway

Objective The main pathological feature of immunoglobulin A nephropathy(IgAN),an autoimmune kidney disease,is the deposition of IgA immune complexes,accompanied by mesangial cell proliferation and elevated urine protein.The Guben Tongluo formula(GTF)is a traditional Chinese medicine prescription,which has predominant protective effects on IgAN.However,the therapeutic mechanism of the GTF in IgAN remains elusive.The present study aimed to determine the effects of GTF in treating IgAN via regulating the TLR4/MyD88/NF-κB pathway.Methods In the present study,lamina propria B lymphocytes were treated with different concentrations of lipopolysaccharide(LPS)(0,1,5,10 and 20 ng/mL).Flow cytometry was used to define positive CD86+CD19+cells.CCK-8 assay was used to examine cell proliferation.RNAi was used to induce TLR4 silencing.qRT-PCR and Western blotting were used to determine gene expression.Results It was found that the LPS dose-dependently increased the content of IgA and galactose-deficient IgA1(Gd-IgA),the levels of TLR4,Cosmc,MyD88 and phosphorylated(p)-NF-κB,and the ratio of CD86+CD19+and IgA-producing B cells.However,the TLR4 knockdown reversed the role of LPS.This suggests that TLR4 mediates the effects of LPS on lamina propria B lymphocytes.Furthermore,the GTF could dose-dependently counteract the effects of LPS and TLR4 overexpression on lamina propria B lymphocytes through the TLR4/MyD88/NF-κB pathway.Conclusion Collectively,these results demonstrate that the GTF can regulate the TLR4/MyD88/NF-κB pathway to treat IgAN model lamina propria B lymphocytes stimulated by LPS.

Correlation Study Between T Lymphocyte Subsets and Rheumatoid Arthritis

Objective:To study the effect of Helicobacter pylori infection on rheumatoid arthritis and T-lymphocyte subpopulations in patients with rheumatoid arthritis and to provide a new method for the treatment of rheumatoid arthritis by removing Helicobacter pylori from patients.Methods:60 patients with rheumatoid arthritis admitted to the hospital from May 2022 to May 2023 were selected for the study,and all patients underwent a 13-carbon urea breath test to detect gastric H.pylori and the test results showed that 20 cases were negative and 40 cases were positive.The 40 positive patients were divided into the treatment group(n=20)and non-treatment group(n=20)by random number table method and the treatment group was given anti-Helicobacter pylori treatment,and the non-treatment group was given maintenance rheumatoid basic treatment,comparing the anti-cyclic citrulline peptide(CCP),DS28 score,peripheral blood T-lymphocyte subsets(CD4^(+)T-lymphocytes,CD8^(+)T-lymphocytes,CD4^(+)/CD8^(+)ratio)before and after the treatment of patients by 13-carbon urea respiration test(pylori-negative group,20 patients)and those who were positive for the treatment of H pylori(pylori-positive group,40 patients).Besides,the correlation of peripheral blood T-lymphocyte subsets and disease activity between treatment and non-treatment groups in the pylori-positive group was identified together with the correlation of DS28 scores,TNF-αlevels,sedimentation and immunoglobulin,lymphocyte subsets in the pylori-positive treatment group and positive non-treatment group as well as the level of globulin,lymphocyte subsets,and peripheral blood lymphocytes before and after treatment.Results:Before treatment,CCP,DS28 score,CD8^(+)T lymphocyte level of the pylori-negative group were lower than that of the positive group,and CD4^(+)T lymphocyte and CD4^(+)/CD8^(+)ratio were higher than that of the positive group(P<0.05);after treatment,the indexes of the pylori-positive group improved,and there was no significant difference in the comparison of the indexes with those of the pylori-negative group(P>0.05);the positive treatment group had a DS28(3.19±1.02)points,positive non-treatment group DS28(5.36±1.85)points,non-treatment group DS28 score and CD4^(+)T lymphocytes,CD4^(+)/CD8^(+)negative correlation with CD8^(+)T lymphocytes showed a positive correlation(P<0.05);before the treatment,pylori-positive treatment group and non-treatment group DS28 scores,TNF-αlevels,peripheral blood T lymphocyte subpopulation levels were not significantly different(P>0.05);after treatment,DS28 score,TNF-αlevel,CD8^(+)T of the treatment group were lower than those of the non-treatment group,and CD4^(+)T lymphocytes and CD4^(+)/CD8^(+)ratio were higher than those of the non-treatment group(P<0.05).Conclusion:H.pylori affects the level of T lymphocyte subsets in patients with rheumatoid arthritis,and there is a certain correlation between the two.Removal of H.pylori can improve the level of T lymphocyte subsets,which is important for the treatment of patients with rheumatoid arthritis.

Activation-induced cell death in B lymphocytes

Upon encountering the antigen (Ag), the immune system can either develop a specific immune response or enter a specific state of unresponsiveness, tolerance. The response of B cells to their specific Ag can be activation and proliferation, leading to the immune response, or anergy and activation-induced cell death (AICD), leading to tolerance. AICD in B lymphocytes is a highly regulated event initiated by crosslinking of the B cell receptor (BCR). BCR engagement initiates several signaling events such as activation of PLCr, Ras, and PI3K, which generally speaking, lead to survival. However, in the absence of survival signals (CD40 or IL-4R engagement), BCR crosslinking can also promote apoptotic signal transduction pathways such as activation of effector caspases, expression of pro-apoptotic genes, and inhibition of pro-survival genes. The complex interplay between survival and death signals determines the B cell fate and, consequently, the immune response.

Competition between TRAF2 and TRAF6 Regulates NF-κB Activation in Human B Lymphocytes

Objective To investigate the role of TNF receptor-associated factor 2 (TRAF-2) and TRAF6 in CD40-induced nuclear factor-κB (NF-κB) signaling pathway and whether CD40 signaling requires TRAF2. Methods Human B cell lines were transfected with plasmids expressing wild type TRAF2 or dominant negative TRAF2,TRAF2-shRNA,or TRAF6-shRNA. The activation of NF-κB was detected by Western blot,kinase assay,transfactor enzyme-linked immunosorbent assay (ELISA),and fluorescence resonance energy transfer (FRET). Analysis of the role of TRAF-2 and TRAF-6 in CD40-mediated NF-κB activity was examined following stimulation with recombinant CD154. Results TRAF2 induced activity of IκB-kinases (IKKα,IKKi/ε),phosphorylation of IκBα,as well as nuclear translocation and phosphorylation of p65/RelA. In contrast,TRAF6 strongly induced NF-κB activation and nuclear translocation of p65 as well as p50 and c-Rel. Engagement of CD154-induced nuclear translocation of p65 was inhibited by a TRAF6-shRNA,but conversely was enhanced by a TRAF2-shRNA. Examination of direct interactions between CD40 and TRAFs by FRET documented that both TRAF2 and TRAF6 directly interacted with CD40. However,the two TRAFs competed for CD40 binding. Conclusions These results indicate that TRAF2 can signal in human B cells,but it is not essential for CD40-mediated NF-κB activation. Moreover,TRAF2 can compete with TRAF6 for CD40 binding,and thereby limit the capacity of CD40 engagement to induce NF-κB activation.

The Role of T Lymphocytes in Bone Remodeling

Bone remodeling is a tightly regulated resorption and formation of bone matrix for physiological processes or to maintain bone function. Bone remodeling involves the synchronized differentiation and activity of bone-related cell types including bone matrix-depositing osteoblasts, bone matrix-resorbing osteoclasts, collagen/extracellular matrix-producing chondrocytes, and the progenitors of these cell types. T and B cells are adaptive immune cells that can influence bone remodeling by directly regulating the function of bone-related cells under normal and pathophysiological conditions. The specific mechanisms through which T cells control remodeling are not well defined. Here, we review the impact and influence of T cells and their products on the differentiation and function of bone cells during bone remodeling. Synthesizing new connections and highlighting potential mechanisms may promote additional avenues of study to elucidate the full role that immune cells play in regulating bone homeostasis.

SUBTYPES OF B LYMPHOCYTES IN PATIENTS WITH AUTOIMMUNE HEMOCYTOPENIA

Objective To investigate the quantities of bone marrow CD5+ B lymphocytes in the patients with autoimmune hemocytopenia and the relationship between quantities of CD5+ B lymphocytes and clinical or laboratorial parameters. Methods Quantities of CD5+ B lymphocytes in the bone marrow of 14 patients with autoimmune hemolytic anemia (AIHA) or Evans syndrome, 22 immunorelated pancytopenia (IRP) patients, and 10 normal controls were assayed by flow cytometry. The correlation between their clinical or laboratorial parameters and CD5+ B lymphocytes was analyzed. Results The quantity of CD5+ B lymphocytes of AIHA/Evans syndrome (34.64%±19.81%) or IRP patients (35.81%±16.83%) was significantly higher than that of normal controls (12.00%±1.97%, P<0.05). However, there was no significant difference between AIHA/Evans syndrome and IRP patients (P>0.05). In all hemocytopenic patients, the quantity of bone marrow CD5+ B lymphocytes showed significantly negative correlation with serum complement C3 level (r=-0.416, P<0.05). In the patients with AIHA/Evans syndrome, the quantity of bone marrow CD5+ B lymphocytes showed significantly positive correlation with serum indirect bilirubin level (r=1.00, P<0.05). In Evans syndrome patients, the quantity of CD5+ B lymphocytes in bone marrow showed significantly positive correlation with platelet-associated immunoglobulin G (r=0.761, P<0.05) and platelet-associated immunoglobulin M (r=0.925, P<0.05). The quantity of CD5+ B lymphocytes in bone marrow of all hemocytopenic patients showed significantly negative correlation with treatment response (tau-b=-0.289, P<0.05), but had no correlation with colony forming unit-erythroid (r=-0.205, P>0.05) or colony forming unit-granulocyte-macrophage colonies (r=-0.214, P>0.05). Conclusions The quantity of bone marrow CD5+ B lymphocytes in the patients with autoimmune hemocytopenia significantly increases and is correlated with disease severity and clinical response, which suggest that CD5+ B lymphocytes might play an important role in the pathogenesis of autoimmune hemocytopenia.

Immunotherapy in pancreatic cancer:Unleash its potential through novel combinations

Pancreatic cancer is the third leading cause of cancer mortality in both men and women in the United States,with poor response to current standard of care,short progression-free and overall survival.Immunotherapies that target cytotoxic T lymphocyte antigen-4,programmed cell death protein-1,and programmed death-ligand 1 checkpoints have shown remarkable activities in several cancers such as melanoma,renal cell carcinoma,and nonsmall cell lung cancer due to high numbers of somatic mutations,combined with cytotoxic T-cell responses.However,single checkpoint blockade was ineffective in pancreatic cancer,highlighting the challenges including the poor antigenicity,a dense desmoplastic stroma,and a largely immunosuppressive microenvironment.In this review,we will summarize available clinical results and ongoing efforts of combining immune checkpoint therapies with other treatment modalities such as chemotherapy,radiotherapy,and targeted therapy.These combination therapies hold promise in unleashing the potential of immunotherapy in pancreatic cancer to achieve better and more durable clinical responses by enhancing cytotoxic T-cell responses.

Analysis of the Peripheral Blood Helper T-Cell 17- Cell Level and Monocyte/Lymphocyte Ratio for Colorectal Cancer Prognosis Prediction

Objective: To investigate the value of peripheral blood helper T cell 17 cell level and monocyte/lymphocyte ratio to predict the prognosis of colorectal cancer patients. Methods: 74 colorectal cancer patients who attended Hospital 960 from January 2021 to January 2022 were retrospectively analyzed. Clinical data of the patients were collected, including gender, age, and histologic type. Immunohistochemical indexes such as Th17 cell level and monocyte/ lymphocyte ratio in the peripheral blood of patients were also collected. The prognosis of patients after treatment, as well as peripheral blood Th17 and MLR levels, were observed and analyzed. Results: After follow-up after treatment, in the final 74 patients, the prognosis was good in 32 patients, accounting for 43.24%, and the prognosis was bad in 42 patients, accounting for 56.76%. There were no significant differences between the average age and tumor diameters of the good prognosis and poor prognosis groups (P > 0.05). However, the TNM staging, intervention taken, differentiation degree, presence of distant metastasis, presence of lymph node metastasis, Th17 level, and MLR level are significantly different between the two groups (P < 0.05). Conclusion: Peripheral blood Th17 and MLR have predictive value for the prognosis of colorectal cancer patients, and high levels of peripheral blood Th17 and MLR imply poor prognosis. The detection of peripheral blood Th17 and MLR levels is simple and convenient and can be used as indicators to provide a reference for the prognostic assessment of colorectal cancer patients.

Effect of Bifidobacterium triple live bacteria on inflammatory factors, oxidative stress and T lymphocyte subsets in patients with ulcerative colitis

Objective: To explore the effect of Bifidobacterium triple live bacteria on inflammatory factors, oxidative stress and T lymphocyte subsets in patients with ulcerative colitis (UC). Method: A total of 90 patients with UC treated in our hospital were selected and randomly divided into the observation group and the control group each with 45 cases. The control group was given Mesalazin Enteric-coated Tablets 1 g/times, 4 times/d, continuous treatment for 1 months:when the clinical symptoms were stable, switched to 500 mg/times, 3 times/d, continuous treatment for 3 months. The observation group on the basis of conventional treatment to give Bifidobacterium triple live bacteria scattered adjuvant therapy (Bifico capsule), 0.84 g/time, 2 times/d, continuous treatment for 3 months. In the two groups, the levels of inflammatory factors (IL-6, IL-10, CRP, TNF-α), oxidative stress markers (MDA, SOD) and T lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+) were compared pre and post treatment. Results: The levels of IL-6, CRP, MDA, TNF-α, CD8+ in both two groups were significantly decreased compared with treatment before;the levels of IL-10, SOD, CD3+, CD4+ and CD4+/CD8+were significantly increased compared with treatment before. After treatment, the levels of serum IL-6, CRP, TNF-α, MDA and CD8+ in observation group with the data (72.17±15.18) pg/mL, (21.52±10.21) mg/mL, (15.98±4.12) pg/mL respectively were decreased more significantly than those data in control group which were (86.55±17.26) pg/mL, (43.02±12.27) mg/L, (22.35±3.67) pg/mL, MDA level (5.89±0.56) nmol/mL in observation group was decreased more significantly than the level in the control group (6.75±0.68) nmol/mL;CD8+level (17.24±3.06)% in observation group was decreased more significantly than the level (19.01±2.62)% in the control group. After treatment, IL-10 level (70.21±6.03) pg/mL in observation group was increased more significantly than the level in the control group (56.48+ 8.67) pg/mL;SOD level (1.84±0.06) U/mL in observation group was increased more significantly than the level in the control group (1.32±0.05) U/mL;the levels of CD3+, CD4+, CD4+/CD8+ in the observation group (57.84±6.07)%;(36.78±4.32)%;(1.92±0.29) were increased more significantly than the level in the control group (54.93±6.87)%;(35.42±5.27)%;(1.89±0.12). Conclusion: Bifidobacterium triple live bacteria scattered adjuvant treatment of ulcerative colitis helps regulate oxidative stress and inflammatory cytokines inhibiting inflammatory reaction and improving enhance function, and can effectively improve the clinical symptoms of patients with UC.

Identification of the epitopes on HCV core protein recognized by HLA-A2 restricted cytotoxic T lymphocytes

AIM: To identify hepatitis C virus(HCV) core protein epitopes recognized by HLA-A2 restricted cytotoxic T lymphocyte (CTL). METHODS: Utilizing the method of computer prediction followed by a 4h(51)Cr release assay confirmation. RESULTS: The results showed that peripheral blood mononuclear cells (PBMC) obtained from two HLA-A2 positive donors who were infected with HCV could lyse autologous target cells labeled with peptide &quot;ALAHGVRAL (core 150-158)&quot;. The rates of specific lysis of the cells from the two donors were 37.5% and 15.8%, respectively. Blocking of the CTL response with anti-CD4 mAb caused no significant decrease of the specific lysis. But blocking of CTL response with anti-CD8 mAb could abolish the lysis. CONCLUSION: The peptide (core 150-158) is the candidate epitope recognized by HLAA2 restricted CTL.

Magnetic Field Emulations of Small Inhibitor RNA: Effects on Implanted GL261 Tumors in C57BL/6 Immune Competent Mice

EMulate Therapeutics has developed a system for emulating the effects of solvated molecules via their magnetic field recordings. Recordings of magnetic field emissions of select small inhibitor RNAs (siRNAs;murine targeting CTLA-4 and murine targeting PD-1) were tested on C57Bl/6 mice implanted subcutaneously with the GL261 murine tumor cell line. A signal composed of concatenated recordings of siRNA molecules targeting the murine CTLA-4 and PD-1 receptors (labeled A2) was used in immune competent C57Bl/6 mice. The mice were flank implanted with the murine glioblastoma cell line GL261. Mice were exposed to the signal continuously (24 hours a day) until tumor volumes reached the designated volume limit. Tumors were excised and analyzed via PAGE/Western blot for the expression of CTLA-4, PD-1, Ki67, Caspase 3, CD4 and CD8. Terminal blood draws were used for CBCs. We report the down regulation of the checkpoint inhibitors CTLA-4 in the exposed mice. Significant tumor volume reduction was observed in mice exposed to the siRNA signal compared to control mice;no adverse events were recorded. Cell blood counts (CBC) and protein expression patterns were observed to correlate with the expected function of protein expression inhibition of the targets.

Costimulation of resting B lymphocytes alters the IL-4-activated IRS2 signaling pathway in a STAT6 independent manner: implications for cell survival and proliferation

IL-4 is an important B cell survival and growth factor. IL-4 induced the tyrosine phosphorylation of IRS2 in resting B lymphocytes and in LPS- or CD40L-activated blasts. Phosphorylated IRS2 coprecipitated with the p85 subunit of PI 3’ kinase in both resting and activated cells. By contrast, association of phosphorylated IRS2 with GRB2 was not detected in resting B cells after IL-4 treatment although both proteins were expressed. However, IL-4 induced association of IRS2 with GRB2 in B cell blasts. The pattern of IL-4- induced recruitment of p85 and GRB2 to IRS2 observed in B cells derived from STAT6 null mice was identical to that observed for normal mice. While IL-4 alone does not induce activation of MEK, a MEKI inhibitor suppressed the IL-4-induced proliferative response of LPS-activated B cell blasts. These results demonstrate that costimulation of splenic B cells alters IL-4-induced signal transduction independent of STAT6 leading to proliferation. Furthermore, proliferation induced by IL-4 in LPS-activated blasts is dependent upon the MAP kinase pathway.

T lymphocyte proportion in Alzheimer’s disease prognosis

Bai et al investigate the predictive value of T lymphocyte proportion in Alzheimer's disease(AD)prognosis.Through a retrospective study involving 62 AD patients,they found that a decrease in T lymphocyte proportion correlated with a poorer prognosis,as indicated by higher modified Rankin scale scores.While the study highlights the potential of T lymphocyte proportion as a prognostic marker,it suggests the need for larger,multicenter studies to enhance generalizability and validity.Additionally,future research could use cognitive exams when evaluating prognosis and delve into immune mechanisms underlying AD progression.Despite limitations inherent in retrospective designs,Bai et al's work contributes to understanding the immune system's role in AD prognosis,paving the way for further exploration in this under-researched area.

Predictors of prognosis in Alzheimer’s disease: The role of cognitive dysfunction, immune abnormalities, and advanced neuroimaging

Alzheimer’s disease(AD)is a grave illness that results in cognitive and social issues.A recent study examined the association between neuroimaging results,cognitive dysfunction,atypical cellular immune function,and poor prognostic factors in AD patients who demonstrated poor prognosis.Poor prognosis was associated with abnormal cellular immune function,extrapyramidal symptoms,altered consciousness,abnormal electroencephalogram,modified Rankin scale,increased neutrophil lymphocyte ratio,and severe pneumonia.The impaired cellular immune function characterized by a reduction in the blood T lym-phocytes’proportion predicted poor prognosis as an independent risk factor in AD.Early initiation and maintenance of AD medications is associated with better outcomes.

Is the neutrophil to lymphocyte ratio associated with liver fibrosis in patients with chronic hepatitis B?

AIM: To determine the association between the neutrophil to lymphocyte(N/L) ratio and the degree of liver fibrosis in patients with chronic hepatitis B(CHB) infection. METHODS: Between December 2011 and February 2013, 129 consecutive CHB patients who were admitted to the study hospitals for histological evaluation of chronic hepatitis B-related liver fibrosis were included in this retrospective study. The patients were divided into two groups based on the fibrosis score: individuals with a fibrosis score of F0 or F1 were included in the "no/minimal liver fibrosis" group, whereas patients with a fibrosis score of F2, F3, or F4 were included in the "advanced liver fibrosis" group. The Statistical Package for Social Sciences 18.0 for Windows was used to analyze the data. A P value of < 0.05 was accepted as statistically significant.RESULTS: Three experienced and blinded pathologists evaluated the fibrotic status and inflammatory activity of 129 liver biopsy samples from the CHB patients. Following histopathological examination, the "no/minimal fibrosis" group included 79 individuals, while the "advanced fibrosis" group included 50 individuals. Mean(N/L) ratio levels were notably lower in patients with advanced fibrosis when compared with patients with no/minimal fibrosis. The mean value of the aspartate aminotransferase-platelet ratio index was markedly higher in cases with advanced fibrosis compared to those with no/minimal fibrosis.CONCLUSION: Reduced levels of the peripheral blood N/L ratio were found to give high sensitivity, specificity and predictive values in CHB patients with significant fibrosis. The prominent finding of our research suggests that the N/L ratio can be used as a novel noninvasive marker of fibrosis in patients with CHB.