Diagnosis of the jejunoileal lymphoma by double-balloon endoscopy

AIM:To investigate the feasibility of double-balloon endoscopy(DBE) to detect jejunoileal lymphoma,compared with fluorodeoxyglucose positron emission tomography(FDG-PET).METHODS:Between March 2004 and January 2011,we histologically confirmed involvement of malignant lymphoma of the jejunoileum in 31 patients by DBE and biopsy.In 20 patients of them,we performed with FDGPET.We retrospectively reviewed the records of these 20 patients.Their median age was 64 years(range 50-81).In the 20 patients,the pathological diagnosis of underlying non-Hodgkin's lymphoma(NHL) comprised follicular lymphoma(FL,n = 12),diffuse large B cell lymphoma(DLBCL,n = 4),mantle cell lymphoma(MCL,n = 2),enteropathy associated T cell lymphoma(ETL,n = 1) and anaplastic large cell lymphoma(ALCL,n = 1).RESULTS:Ten cases showed accumulation by FDGPET(50%).FDG-PET was positive in 3 of 12 FL cases(25%) while in 7 of 8 non-FL cases(88%,P < 0.05).Intestinal FL showed a significantly lower rate of positive FDG-PET,in comparison with other types of lymphoma.Cases with endoscopically elevated lesions(n = 10) showed positive FDG-PET in 2(20%),but those with other type NHL did in 8 of 10(80%,P < 0.05).When the cases having elevated type was compared with those not having elevated type lesion,the number of cases that showed accumulation of FDG was significantly smaller in the former than in the latter.CONCLUSION:In a significant proportion,small intestinal involvement cannot be pointed out by FDG-PET.Especially,FL is difficult to evaluate by FDG-PET but essentially requires DBE.

ALTERATION OF HB-EGF IN PSORIATIC EPIDERMIS WITH THE TREATMENT OF RETINOID ACID

Objective To investigate the mechanism of tazarotene in active psoriasis vulgaris. Methods HB EGF protein in active psoriatic lesions before and 10 days after the treatment of tazarotene was detected by immunohistochemistry. Results There was nearly no expression of HB EGF in psoriatic lesions (9.1%), but after the treatment by tazarotene, there was expression of HB EGF not only in basal layer (95.5%), but also focal expression in suprabasal layers of epidermis (77.3%) . Conclusion Tazarotene inhibit proliferation and induce apoptosis of keratinocytes through upregulating expression of HB EGF in psoriatic epidermis.

EFFECT OF NICOTINE ON GROWTH AND EXPRESSION OF APOPTOSIS-RELATED GENES OF SMALL CELL LUNG CANCER (SCLC) CELL

Objective: To investigate the effect of nicotine on growth and apoptosis-related gene expression of human small lung cancer cell. Methods: NCI-H446 cell line was cultured in the presence of various concentrations (1～1000 ng/ml) of nicotine for 48 h. MTT was applied to evaluate the effect of nicotine on the growth of NCL-H446, small cell lung carcinoma (SCLC) cell line. After NCI-H446 cells were treated with 100 ng/ml for 48 h, human apoptosis-related gene cDNA expression profile microarray was used to detect the expression of 451 apoptosis-related genes in NCL-H446 cell line. Results: Significant proliferation promotion of nicotine (1～10 ng/ml) on NCI-LH446 cells were observed, but with decreased promotion effect with increased concentration of nicotine in culture. Growth inhibition rates for 1, 10, 100 and 1000 ng/m1 nicotine were -91.0%, -41.8%, -40.0% and 27.3% respectively. Microarray detection showed that significantly different expressions were found in71 of 451 apoptosis-related genes. 38 apoptosis-promoting gene and 30 apoptosis-inhibiting genes were up-regulated significantly (cy3/cy5>2.0), and only 3 showed significant down-regulation (cy3/cy5<0.5). Conclusion: Nicotine may promote growth of human SCLC cell, and regulate expression of apoptosis-related genes.

Dominating expression of negative regulatory factors downmodulates major histocompatibility complex Class-Ⅱexpression on dendritic cells in chronic hepatitis C infection

AIM: To elucidate the molecular mechanisms leading to development of functionally impaired dendritic cells(DCs) in chronic hepatitis C(CHC) patients infected with genotype 3 virus.METHODS: This prospective study was conducted on the cohorts of CHC individuals identified as responders or non-responders to antiviral therapy. Myeloid DCs were isolated from the peripheral blood of each subject using CD1c(BDCA1)+ DC isolation Kit. Monocytes from healthy donor were cultured with DC growth factors such as IL-4 and GM-CSF either in the presence or absence of hepatitis C virus(HCV) viral proteins followed by LPS stimulation. Phenotyping was done by flowcytometry and gene expression profiling was evaluated by real-time PCR.RESULTS: Non-responders [sustained virological response(SVR)-ve] to conventional antiviral therapy had significantly higher expression of genes associated with interferon responsive element such as IDO1 and PD-L1(6-fold) and negative regulators of JAK-STAT pathway such as SOCS(6-fold) as compared to responders(SVR+ve) to antiviral therapy. The downregulated genes in non-responders included factors involved in antigen processing and presentation mainly belonging to major histocompatibility complex(MHC) Class-Ⅱ family as HLA-DP, HLA-DQ(2-fold) and superoxide dismutase(2-fold). Cells grown in the presence of HCV viral proteins had genes downregulated for factors involved in innate response, interferon signaling, DC maturation and co-stimulatory signaling to T-cells, while the genes for cytokine signaling and Toll-like receptors(4-fold) were upregulated as compared to cells grown in absence of viral proteins.CONCLUSION: Underexpressed MHC class-Ⅱ genes and upregulated negative regulators in non-responders indicate diminished capacity to present antigen and may constitute mechanism of functionally defective state of DCs.

Liver dysfunction during COVID-19 pandemic:Contributing role of associated factors in disease progression and severity

In December 2019,a new strain of coronavirus was discovered in China,and the World Health Organization declared it a pandemic in March 2020.The majority of people with coronavirus disease 19(COVID-19)exhibit no or only mild symptoms such as fever,cough,anosmia,and headache.Meanwhile,approximately 15%develop a severe lung infection over the course of 10 d,resulting in respiratory failure,which can lead to multi-organ failure,coagulopathy,and death.Since the beginning of the pandemic,it appears that there has been consideration that preexisting chronic liver disease may predispose to deprived consequences in conjunction with COVID-19.Furthermore,extensive liver damage has been linked to immune dysfunction and coagulopathy,which leads to a more severe COVID-19 outcome.Besides that,people with COVID-19 frequently have abnormal liver function,with more significant elevations in alanine aminotransferase and aspartate aminotransferase in patients with severe COVID-19 compared to those with mild/moderate disease.This review focuses on the pathogenesis of severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection in the liver,as well as the use of liver chemistry as a prognostic tool during COVID-19.We also evaluate the findings for viral infection of hepatocytes,and look into the potential mechanisms behind SARS-CoV-2-related liver damage.

Unfolding of HIV Epidemic and Spectrum of AIDS in North India

The review traces the unfolding of HIV epidemic in North India. The first few cases were reported in 1989 in Indians returning from African countries like Uganda, Zambia and a trickle from USA. Subsequently the cases started pouring from coastal areas of Mumbai, Chennai and finally the virus spread all over through rail and road. In the North eastern region or the golden triangle, IV drug users formed a major group. Using a simple peptide ELISA, it was documented that the virus belonged to the NOF strain. This was much before clades were identified using molecular analysis. It appears that the HIV virus followed the drug (mandrax) route between Mumbai and South Africa. An alarming rise was observed among truck drivers fuelling HIV in Punjab villages who indulged in promiscuous behavior in road side making shift brothels near eating kiosks. Special customs in the state also flared the spread. During the early epidemic a very high prevalence was shown in blood transfused individuals (12.5%) which dropped to 2% -3% after aggressive measures taken by the NACO. While HIV positivity rates plateaued in some states by 2004, infection in Punjab continued to rise even after 2005. Kaposi sarcoma is almost unknown in Indian patients while TB and candida formed major co-infections. In one study, subtype V3 -V5 region chimeras of Indian clade C and clade B replicated freely in peripheral blood mononuclear cells (PBMC) and macrophages and showed higher HIV replication. Opt-out screening was started in an emergency setting in a tertiary care hospital. The positivity rate was 20/per thousand. Thus a large number of patients would have been missed if opt-out screening was not resorted to.

Increased Activity of NK Cells and Plasmacytoid Dendritic Cells in HIV-Exposed Seronegative (ESN) Individuals

The mechanisms involved in resistance to HIV-1 infection, especially the role of innate immune response, have not been thoroughly explored in individuals who are repeatedly exposed to HIV-1, but do not get the infection, termed as Exposed sero-negative or ESN. Frequency and activation state of natural killer (NK) cells and plasmacytoid dendritic cells (pDC) in ESNs from North India were compared with those in recently infected HIV positives (RHIV), chronically infected HIV positives (HIV+) and healthy controls (HC). The activation state of NK cells in terms of cytokine response (IFNγ & TNFα) was significantly higher in ESNs compared to the healthy controls, recently infected HIV+ and chronically infected HIV+. Although the number of circulating pDC in different study groups was not significantly different, yet these cells seem to have significantly higher activation state in terms of IFNα production (ex-vivo in response to CpG ODN) in ESNs when compared with other groups. Increased activation status of NK cells and pDC in Exposed but Seronegative individuals indicates their continuous stimulation with HIV antigens due to regular exposure with infected partners and which might be imparting resistance to viral infection in these individuals.

Low Levels of Complement Factor C4 Not Always Implicate Disease Activity in Systemic Lupus Erythematosus

A lupus patient with a clinically quiescent disease stage will be described who had severely depressed C4 levels while levels of C3 en CH50 were normal. Additional testing revealed a homozygous C4Aisotype deficiency as the cause of the very low C4 levels. It should be emphasized that in SLE, a (very) low C4 level does not always means (subclinical) disease activity.

Management of SARS-CoV-2 infection is a major challenge in patients with lymphoid malignancies: Warrants a clear therapeutic strategy

Patients with lymphoid malignancies are at a higher risk of coronavirus disease 2019(COVID-19)infection due to their immunocompromised state and results in higher mortality rates in these patients.Anti-CD 20 therapy is one of the leading causes of immunosuppression that worsens in COVID-19 cases.COVID-19 vaccines,on the other hand,appear to be less beneficial to these patients.Appropriate treatment and recommendations are required for these COVID-19 patients with lymphoid malignancies.

Gender differences in the relationship between alcohol consumption and gastric cancer risk are uncertain and not well-delineated

The role of alcoholic and other beverage consumption in the etiology of gastric cancer is unknown.Several studies have summarized and established a significant association between heavy alcohol consumption and gastric cancer risk,but evidence on alcohol-related cancer risk is conflicting.

SARS-CoV-2 infection in people with pre-existing liver disease:Further research is warranted

Patients with severe liver disease who have been infected with severe acute respiratory syndrome coronavirus-2(coronavirus disease 2019)frequently develop acute respiratory distress syndrome and multiple organ failure,with a high mortality rate,as a result of the hyper-proinflammatory state known as the cytokine storm.Clinicians must recognize cytokine storms earlier to avoid intensive care admission and multi-organ damage,a critical life-threatening condition with prognostic and therapeutic implications.

Viral hepatitis: A global burden needs future directions for the management

Viral hepatitis is an acute or chronic liver disease due to the infection from Hepatitis A,B,C,D and E viruses.It can cause severe liver damage such as cirrhosis,liver failure and liver cancer.To avoid such fatal complications,hepatitis patients must be diagnosed,pathologized and treated as soon as possible.Furthermore,these hepatitis viruses infect through different routes,resulting in distinct disease pathologies,severity and even the need for specific treatment strategies to combat the infection.

Bacterial and fungal co-infection is a major barrier in COVID-19 patients:A specific management and therapeutic strategy is required

Microbial co-infections are another primary concern in patients with coronavirus disease 2019(COVID-19),yet it is an untouched area among researchers.Preliminary data and systematic reviews only show the type of pathogens responsible for that,but its pathophysiology is still unknown.Studies show that these microbial co-infections are hospital-acquired/nosocomial infections,and patients admitted to intensive care units with invasive mechanical ventilation are highly susceptible to it.Patients with COVID-19 had elevated inflammatory cytokines and a weakened cell-mediated immune response,with lower CD4+T and CD8+T cell counts,indicating vulnerability to various co-infections.Despite this,there are only a few studies that recommend the management of coinfections.

Regulation of immune cell responses by semaphorins and their receptors

Semaphorins were originally identified as axon guidance factors involved in the development of the neuronal system. However, accumulating evidence indicates that several members of semaphorins, so-called ＇immune semaphorins＇, are crucially involved in various phases of immune responses. These semaphorins regulate both immune cell interactions and immune cell trafficking during physiological and pathological immune responses. Here, we review the following two functional aspects of semaphorins and their receptors in immune responses： their functions in cell-cell interactions and their involvement in immune cell trafficking.

Utility of direct 3D co-culture model for chondrogenic differentiation of mesenchymal stem cells on hyaluronan scaffold(Hyaff-11)

This study presents direct 2D and 3D co-culture model of mesenchymal stem cells(MSCs)line with chondrocytes isolated from patients with osteoarthritis(unaffected area).MSCs differentiation into chondrocytes after 14,17 days was checked by estimation of collagen Ⅰ,Ⅱ,Ⅹ,aggrecan expression using immunohistochemistry.Visualization,localization of cells on Hyaff-11 was performed using enzymatic technique and THUNDER Imaging Systems.Results showed,that MSCs/chondrocytes 3D co-culture induced suitable conditions for chondrocytes grow and MSCs differentiation than 2D monoculture.Despite that differentiated cells on Hyaff-11 expressed collagen Ⅹ,they showed high collagen Ⅱ(80%)and aggrecan(60%)expression with simultaneous decrease of collagen Ⅰ expression(10%).The high concentration of differentiated cells on Hyaff-11,indicate that this structure has an impact on cells cooperation and communication.In conclusion,we suggest that high expression of collagen Ⅱ and aggrecan in 3D co-culture model,indicate that cooperation between different subpopulations may have synergistic impact on MSCs chondrogenic potential.Revealed the high concentration and localization of cells growing in deeper layers of membrane in 3D co-culture,indicate that induced microenvironmental enhance cell migration within scaffold.Additionally,we suggest that co-culture model might be useful for construction a bioactive structure for cartilage tissue regeneration.