The role of Th-17 cells and IL-17 in the metastatic spread of breast cancer: As a means of prognosis and therapeutic target.

Metastatic breast cancer is one of the most common and well-known causes of death for women worldwide. The inflammatory tumor cell and other cancer hallmarks dictate the metastatic form and dissemination of breast cancer. Taking these into account, from various components of the tumor microenvironment, a pro-inflammatory infiltrative cell known as Th-17 plays an immense role in breast cancer proliferation, invasiveness, and metastasis. It has been demonstrated that IL-17, a pleiotropic pro-inflammatory cytokine generated by Th-17, is upregulated in a metastatic form of breast cancer. Recent research updates stated that chronic inflammation and mediators like cytokines and chemokines are causative hallmarks in many human cancers, including breast cancer. Therefore, IL-17 and its multiple downward signaling molecules are the centers of research attention to develop potent treatment options for cancer. They provide information on the role of IL-17-activated MAPK, which results in tumor cell proliferation and metastasis via NF-kB-mediated expression of MMP signaling. Overall, this review article emphasizes IL-17A and its intermediate signaling molecules, such as ERK1/2, NF-kB, MMPs, and VEGF, as potential molecular targets for the prevention and treatment of breast cancer.

Elevated KIR expression and diminished intensity of CD7 on NK cell subsets among treatment naïve HIV infected Ethiopians.

Natural killer (NK) cells are crucial effector cells of the innate immune response to viral infections, including HIV, through cytolytic activity and the production of cytokines with anti-HIV activities. We recruited 15 treatment naïve HIV patients and 16 healthy controls (HC) to assess NK cell subsets or expression of multiple markers by flow cytometry. The frequency of circulating CD56brightCD16-ve and CD56dimCD16bright NK cell subsets was significantly lower among the HIV group than in HC. The CD56-veCD16bright subset was higher in HIV patients, but this was only apparent when gated among total NK cells, not total lymphocytes. NK cells among HIV participants also showed a lower and higher frequency of CD8 and HLA-DR expressing cells, respectively. In addition, CD7 median fluorescent intensity and CD2+CD7- frequencies were significantly lower in HIV patients. A distinct population of KIR3DL1/S1 cells was unexpectedly higher among CD56brightCD16-ve NK cells in HIV patients. In conclusion, this study in the Ethiopian setting confirms many previous findings, but the down-regulation of CD7 and enhanced KIR3DL1/S1 within the CD56bright subsets have not been widely reported among HIV patients and merit further research.

Detection of Mycobacterium tuberculosis and rifampicin resistance by Xpert® MTB/RIF assay among presumptive tuberculosis cases at Jimma University Medical Center, Southwest Ethiopia.

BACKGROUND: Rapid diagnosis of tuberculosis (TB) and detection of drug resistance are very important for timely and appropriate management of patients. Xpert MTB/RIF assay is approved for use in TB and rifampicin-resistance diagnosis. However, data are limited on the impact of Xpert MTB/RIF assay under routine clinical settings with a heterogeneous group of patients and sample types in Ethiopia. METHODS: A retrospective study was carried out in 2220 presumptive TB cases at Jimma University Medical Center. Data were gathered from the registration logbook using formatted data extraction tools and double entered to epidata version 3.1 and further transported to SPSS version 20 for analysis. Associations were determined using the Chi-square test and P-value <0.05 was considered statistically significant. RESULTS: Of 2220 cases enrolled, 1665 (75%) were adults and the remaining 555 (25%) were children aged less than 14 years. The majority, 1964 (88.46%), had pulmonary manifestation and 256 (11.54%) had extrapulmonary involvements. The overall, frequency of Mycobacterium tuberculosis (MTB) was 9.3% (206/2220), among this 10.27% (171/1665) and 6.3% (35/555) were adults and children, respectively. M. tuberculosis was detected from 171 (8.75%) of pulmonary patients and 35 (13.28%) of extrapulmonary manifested patients. Out of 206 M. tuberculosis positive cases, 7(3.4%) were rifampicin-resistant: four from pulmonary tuberculosis (PTB) patients and three from EPTB patients. In the Chi-square test, the age group of 15-24 years, previous history of TB, pus/lymph node sample, and being HIV positive were significantly associated with TB positivity by Xpert MTB/RIF (P-value <0.001). CONCLUSION: These data suggest that the overall frequency of M. tuberculosis and rifampicin resistance was found to be relatively low compared to the previous reports in Ethiopia. Nevertheless, better diagnostic tools and approaches are still vital to halt the burden of TB and drug-resistant TB in the country.

Effect of Leptin on Chronic Inflammatory Disorders: Insights to Therapeutic Target to Prevent Further Cardiovascular Complication.

In response to obesity-associated chronic inflammatory disorders, adipose tissue releases a biologically active peptide known as leptin. Leptin activates the secretion of chemical mediators, which contribute to the pathogenesis of chronic inflammatory disorders, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and psoriasis. Conversely, adiposity and obesity are the major aggravating risk factors in the pathogenesis of metabolic syndrome (MetS), including type II diabetes mellitus and obesity-associated hypertension. Elevated level of leptin in obesity-associated hypertension causes an increase in the production of aldosterone, which also results in elevation of arterial blood pressure. Hyperleptinemia is associated with the progress of the atherosclerosis through secretion of pro-inflammatory cytokines, like interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), IL-17, and other cytokines to promote inflammation. The release of those cytokines leads to chronic inflammatory disorders and obesity-associated MetS. Thus, the aberrant leptin level in both MetS and chronic inflammatory disorders also leads to the complication of cardiovascular diseases (CVD). Therapeutic target of leptin regarding its pro-inflammatory effect and dysregulated sympathetic nervous system activity may prevent further cardiovascular complication. This review mainly assesses the mechanism of leptin on the pathogenesis and further cardiovascular risk complication of chronic inflammatory disorders.

Association of IL-10 (- 1082 A/G) and IL-6 (- 174 G/C) gene polymorphism with type 2 diabetes mellitus in Ethiopia population.

BACKGROUND: Interleukin (IL)-6 and IL-10 are the most important cytokine with pro and anti-inflammatory activities, respectively. Dysregulation of IL-6 and IL-10 are associated with increased risk of developing Type 2 Diabetes Mellitus (T2DM). Despite this, a fundamental understanding of both cytokine gene polymorphisms with its expression is critical in understanding of cellular mechanism of insulin resistance as well as T2DM intervention. Therefore, this study aimed to assess IL-6 (- 174 G/C) and IL-10 (- 1082 A/G) gene polymorphism, and its association with T2DM, North West Ethiopia. METHODS: A comparative cross-sectional study from January to May 2018 was conducted on study participants with T2DM and apparently healthy controls. Deoxyribonucleic acid (DNA) extraction and genotyping was carried out by using amplification refractory mutation system polymerase chain reaction to detect polymorphism of IL-6 and IL-10 gene at the position - 174 and - 1082, respectively. The logistic regression model was fitted to assess the association of between cytokine gene polymorphisms and T2DM. Odds ratio with 95% CI was determined to assess the presence and strength of association between the explanatory variables and outcome variable. A P-value < 0.05 was considered as statistically significant. RESULT: Participants carrying the GG genotype of IL-6 (- 174) (OR (95% CI) = 4.61 (2.07-10.54) was a high likelihood of having T2DM compared to those carrying the CC and AA genotypes. AA and AG genotypes of IL-10 (- 1082) were at lower odd of developing T2DM compared to those carrying the GG genotype. In addition, individuals carrying the G allele of IL-6 (- 174) have 2.82-fold odds of developing T2DM compared to individuals carrying the C allele (OR (95% CI) =2.81 (1.78-4.50)). CONCLUSION: Our study revealed that genetic polymorphisms of IL-6 (- 174) GG genotype is the potential host genetic risk factors to T2DM. While, IL-10 (- 1082) AA genotype is negatively associated with T2DM. Therefore, IL-6 (- 174) and IL-10 (- 1082) genetic variation may be considered as a biomarker for early screening and diagnosis of T2DM.

Hyperuricemia and Its Associated Factors Among Adult Staff Members of the Ethiopian Public Health Institute, Ethiopia.

BACKGROUND: Hyperuricemia is related not only to an increased risk of gouty arthritis but also to an increased risk of cardiovascular diseases, resistant hypertension, insulin resistance and progression of type 2 diabetes mellitus. However, to the best of our knowledge, the prevalence of hyperuricemia and its associated factors have rarely been assessed in Ethiopian populations. Therefore, this study aimed to determine the prevalence of hyperuricemia and its associated factors among adult staff members of the Ethiopian Public Health Institute. METHODS: An institution-based cross-sectional study was conducted from July 1 to October 28, 2018. A total of 402 study participants were selected using a simple random sampling technique. An interviewer-administered questionnaire was used to collect the data. A blood sample of approximately 5 mL was collected from each study participant after overnight fasting through standardized methods for biochemical tests, and analyses were carried out with an automated COBAS 6000 analyzer. Data analysis was performed by SPSS version 20 software. The factors associated with the outcome variable were identified by bivariable and multivariable logistic regression analyses, and a p value <0.05 was used to declare statistical significance. RESULTS: The mean age of the study participants was 37.13±10.5 (mean ± SD), and 51.5% of the participants were male. The overall prevalence of hyperuricemia (>5.7 mg/dL for females and >7 mg/dL for males) was found to be 31.0%. The multivariable logistic analysis revealed that age (AOR=1.59, 95% CI 1.01-2.78), sex (AOR=1.66, 95% CI 1.02-2.70), cigarette smoking (AOR=2.05, 95% CI 1.01-4.19) and serum low-density lipoprotein (LDL) (AOR=1.70, 95% CI 1.01-2.87) were significantly associated with hyperuricemia. CONCLUSION: The prevalence of hyperuricemia was relatively high compared to similar studies. Early screening for hyperuricemia in the general population, especially in those who are smokers, of older age and with high serum LDL levels, is vital to control its adverse effects at an early stage.

Genetic Polymorphism of Tumor Necrosis Factor-Alpha, Interferon-Gamma and Interleukin-10 and Association With Risk of Mycobacterium Tuberculosis Infection.

BACKGROUND: Mycobacterium tuberculosis has become the leading cause of morbidity and death in humans worldwide. Thus, genetic variability of the host plays a major role in human susceptibility to the pathogen, among others. Therefore, the objective of this finding was to assess the association of genetic polymorphisms of cytokines with tuberculosis infection. METHOD: A cross-sectional study was conducted between January and May 2018. Five ml of whole blood was collected and extracted the genomic DNA through simple salting out method. The patterns of genetic polymorphism were determined by amplification refractory method PCR using specific primers. Finally, the PCR run on electrophoresis of agarose gel and the band was visualized under UV light. A logistical regression model has been adapted to assess the association of genetic polymorphisms with tubercular infection. In order to determine the association between the explanatory and outcome variable, the odds ratio with 95% CI was calculated. P < 0.05 is a statistically significant value. RESULT: In present study, the frequency of TNF-α -308 G allele and GG genotype OR (95% CI)= 0.20 (0.11-0.37), and OR (95% CI)= 0.29 (0.18-0.46)), respectively) and IFN-γ +874 A allele and AA genotype OR (95% CI)= 3.80 (2.11-6.86) and (OR (95% CI)= 1.61(1.13-2.28), respectively) were significantly associated with tuberculosis incidence. In contrast, there is no significant correlation between IL-10 -1082 A and AA of allele and genotype, respectively in tuberculosis patients (p > 0.05) was evident. CONCLUSION: From our finding, the genetic variability of TNF-α -308 A and IFN-γ +874 alleles are the potent host genetic risk factors associated with tuberculosis infection.

Preparedness and Responses of Healthcare Providers to Combat the Spread of COVID-19 Among North Shewa Zone Hospitals, Amhara, Ethiopia, 2020.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging respiratory disease that is caused by a novel coronavirus and was first detected in December 2019 in Wuhan, China. The disease is highly infectious, and its main clinical symptoms include fever, dry cough, fatigue, myalgia, and dyspnea. Healthcare providers are in front in fighting the coronavirus spread by making themselves the risk of contracting the disease. OBJECTIVE: To assess the preparedness and responses of healthcare providers to combat the spread of COVID-19 among North Shewa Zone Hospitals, Amhara, Ethiopia. METHODS: Facility-based cross-sectional study was conducted from April to May 2020 among 422 healthcare providers in the North Shewa Zone, Amhara, Ethiopia using a self-administered questionnaire. Study subjects were selected through systematic random sampling based on their proportional distribution of sample size to each hospital. A structured questionnaire was used to collect the data. The data were coded and entered into the Epi data 4.2.1 version and the analysis was carried out in Statistical Package for Social Science 25 versions. RESULTS: Four hundred four participants involved in the study have been given a response rate of 95.7%. The self-satisfaction of healthcare providers revealed 301 (74.5%) of study participants feel unsafe in their workplace. Two-third, 260 (64.4%), of them responded that they feel anxious while working with febrile patients. Nearly one-third (31%), 27.4%, 15.9%, 14.5%, 14.2% of HCPs had access to gloves, facemask, goggle, shoe, and apron respectively in hospitals. CONCLUSION: Protecting healthcare workers is a public health priority. Access to essential personal protective equipment during the COVID-19 pandemic was limited. The poor perception of healthcare professionals about not having enough support from medical institutions and public health authorities raises the need to urgently implement strategies to protect healthcare workers in the time of the COVID-19 pandemic.

Helminth Induced Immunoregulation and Novel Therapeutic Avenue of Allergy.

Allergic diseases are increasing at an alarming rate worldwide, particularly in developed countries. In contrast, there is a decrease in the prevalence of helminthic infections and other neglected diseases. The hygiene hypothesis elaborates parasitic infection, and allergy-associated diseases have an inverse relationship. Acute helminthic infection and allergic reaction stimulate Type 2 helper cells (Th2) immune response with up-regulation of cytokines IL-4-, IL-5-, and IL-13-mediated IgE and mast cell production, as well as eosinophilia. However, people who chronically suffer from helminthic infections are demarcated through polarized Th2 resulting in alternative macrophage activation and T regulatory response. This regulatory system reduces allergy incidence in individuals that are chronically diseased through helminth. As a result, the excretory-secretory (ES) substance derived from parasites and extracellular vesicular components can be used as a novel therapeutic modality of allergy. Therefore, the aim of this review meticulously explored the link between helminth infection and allergy, and utilization of the helminth secretome for therapeutic immunomodulation.

Role of Caspase-1 in the Pathogenesis of Inflammatory-Associated Chronic Noncommunicable Diseases.

Caspase-1 is the first and extensively studied inflammatory caspase that is activated through inflammasome assembly. Inflammasome is a cytosolic formation of multiprotein complex that aimed to start inflammatory response against infections or cellular damages. The process leads to an auto-activation of caspase-1 and consequent maturation of caspase-1 target molecules such as interleukin (IL)-1ß and IL-18. Recently, the role of caspase-1 and inflammasome in inflammatory-induced noncommunicable diseases (NCDs) like obesity, diabetes mellitus (DM), cardiovascular diseases (CVDs), cancers and chronic respiratory diseases have widely studied. However, their reports are distinct and even they have reported contrasting role of caspase-1 in the development and progression of NCDs. A few studies have reported that caspase-1/inflammasome assembley has a protective role in the initiation and progression of these diseases through the activation of the noncanonical caspase-1 target substrates like gasdermin-D and regulation of immune cells. Conversely, others have revealed that caspase-1 has a direct/indirect effect in the development and progression of several NCDs. Therefore, in this review, we systematically summarized the role of caspase-1 in the development and progression of NCDs, especially in obesity, DM, CVDs and cancers.

Inflammation Mediated Hepcidin-Ferroportin Pathway and Its Therapeutic Window in Breast Cancer.

Experimental and clinical data strongly support that iron is an essential element which plays a big role in cancer biology. Thus, hepcidin (Hp) and ferroportin (Fpn) are molecules that regulate and maintain the metabolism of iron. A peptide hormone hepcidin limits recycled and stored iron fluxes in macrophage and hepatic hepatocyte, respectively, to the blood stream by promoting degradation of the only iron exporter, Fpn, in the target cells. Moreover, the inflammatory microenvironment of breast cancer and altered hepcidin/ferroportin pathway is intimately linked. Breast cancer exhibits an iron seeking phenotype that is accomplished by tumor-associated macrophage (TAM). Because macrophages contribute to breast cancer growth and progression, this review will discuss TAM with an emphasis on describing how TAM (M2Ф phenotypic) interacts with their surrounding microenvironment and results in dysregulated Hp/Fpn and pathologic accumulation of iron as a hallmark of its malignant condition. Moreover, the underlying stroma or tumor microenvironment releases significant inflammatory cytokines like IL-6 and bone morphogenetic proteins like BMP-2 and 6 leading in aberrant Hp/Fpn pathways in breast cancer. Inflammation is primarily associated with the high intracellular iron levels, deregulated hepcidin/ferroportin pathway, and its upstream signaling in breast cancer. Subsequently, scholars have been reported that reducing iron level and manipulating the signaling molecules involved in iron metabolism can be used as a promising strategy of tumor chemotherapy. Here, we review the key molecular aspects of iron metabolism and its regulatory mechanisms of the hepcidin/ferroportin pathways and its current therapeutic strategies in breast cancer.

Role of Stem-Cell Transplantation in Leukemia Treatment.

Stem cells (SCs) play a major role in advanced fields of regenerative medicine and other research areas. They are involved in the regeneration of damaged tissue or cells, due to their self-renewal characteristics. Tissue or cells can be damaged through a variety of diseases, including hematologic and nonhematologic malignancies. In regard to this, stem-cell transplantation is a cellular therapeutic approach to restore those impaired cells, tissue, or organs. SCs have a therapeutic potential in the application of stem-cell transplantation. Research has been focused mainly on the application of hematopoietic SCs for transplantation. Cord blood cells and human leukocyte antigen-haploidentical donors are considered optional sources of hematopoietic stem-cell transplantation. On the other hand, pluripotent embryonic SCs and induced pluripotent SCs hold promise for advancement of stem-cell transplantation. In addition, nonhematopoietic mesenchymal SCs play their own significant role as a functional bone-marrow niche and in the management of graft-vs-host disease effects during the posttransplantation process. In this review, the role of different types of SCs is presented with regard to their application in SC transplantation. In addition to this, the therapeutic value of autologous and allogeneic hematopoietic stem-cell transplantation is assessed with respect to different types of leukemia. Highly advanced and progressive scientific research has focused on the application of stem-cell transplantation on specific leukemia types. We evaluated and compared the therapeutic potential of SC transplantation with various forms of leukemia. This review aimed to focus on the application of SCs in the treatment of leukemia.

Role of IFN and Complements System: Innate Immunity in SARS-CoV-2.

The critical role of the innate immune system has been confirmed in driving local and systemic inflammation and the cytokine release storm in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This dysregulated immune response is focused on interferon (IFN) and complement activation, which are crucial for the development of metabolic inflammation, local lung tissue damage, and systemic multi-organ failure. IFNs control viral infections by inducing expression of IFN-stimulated genes (ISGs) that restrict distinct steps of viral replication. Therefore, in this review article, we propose the mechanism of SARS-CoV-2-associated acute respiratory disease syndrome, and assess treatment options by considering IFNs and by targeting IFN-antagonist SARS-CoV-2 virulent gene products. Furthermore, we elaborate on the mechanism of the amplified complement-mediated inflammatory cytokine storm, and propose an antiviral and immunotherapeutic strategy against coronavirus disease 2019 (COVID-19).

Knowledge, Attitude and Practice Towards COVID-19 Among Chronic Disease Patients at Addis Zemen Hospital, Northwest Ethiopia.

PURPOSE: The recent outbreak of coronavirus disease 2019 (COVID-19) is the worst global crisis after the Second World War. Since no successful treatment and vaccine have been reported, efforts to enhance the knowledge, attitudes, and practice of the public, especially the high-risk groups, are critical to manage COVID-19 pandemic. Thus, this study aimed to assess knowledge, attitude, and practice towards COVID-19 among patients with chronic disease. PATIENTS AND METHODS: A cross-sectional study was conducted among 404 chronic disease patients from March 02 to April 10, 2020, at Addis Zemen Hospital, Northwest Ethiopia. Both bivariable and multivariable logistic regression analyses with a 95% confidence interval were fitted to identify factors associated with poor knowledge and practice towards COVID-19. The adjusted odds ratio (AOR) was used to determine the magnitude of the association between the outcome and independent variables. P-value <0.05 was considered statistically significant. RESULTS: The mean age of the participants was 56.5±13.5. The prevalence of poor knowledge and poor practice was 33.9% and 47.3%, respectively. Forty-one percent of the participants perceived that avoiding of attending a crowded population is very difficult. Age (AOR=1.05, (95% CI (1.01-1.08)), educational status of "can't read and write" (AOR=7.1, 95% CI (1.58-31.93)), rural residence (AOR=19.0, 95% CI (6.87-52.66)) and monthly income (AOR=0.8, 95% CI (0.79-0.89)) were significantly associated with poor knowledge. Being unmarried (AOR=3.9, 95% CI (1.47-10.58)), cannot read and write (AOR=2.7, 95% CI (1.03-7.29)), can read and write (AOR=3.5, 95% CI (1.48-8.38)), rural residence (AOR=2.7, 95% CI (1.09-6.70)), income of <7252 Ethiopian birr (AOR=2.3, 95% CI (1.20-4.15)) and poor knowledge (AOR=8.6, 95% CI (3.81-19.45)) were significantly associated with poor practice. CONCLUSION: The prevalence of poor knowledge and poor practice was high. Leaflets prepared in local languages should be administered and health professionals should provide detailed information about COVID-19 to their patients.

Hepatocellular Expression of SIRT1 and Its Effect on Hepatocellular Carcinoma Progression: A Future Therapeutic Perspective.

Hepatocellular carcinoma (HCC) is an aggressive primary hepatic malignancy with a significant morbidity and mortality rate. Although chemotherapy along with surgical incision is believed to be an effective therapeutic approach, to date recurrence is being lifted a major concern. Thus, identifying another best therapeutic approach is becoming the main aim of physicians and scholars. In support of this, recently, several studies reported a significant observation of Sirtuin1 (SIRT1) overexpression in the malignant tumor cells, including HCC. As a result, they believed that overexpression of SIRT1 may have an effect on the progression of HCC by targeting growth and/or apoptotic controlling transcriptional factors/signaling pathways. Similarly, other reports confirmed that SIRT1 inhibition had a direct or indirect role in the control of tumor cell growth and metastasis. Therefore, inhibiting the expression and activity of SIRT1 might have a therapeutic effect to handle HCC. However, there are a limited number of reviews regarding the issue, and here, we summarized hepatocellular expression of SIRT1 and its role on HCC progression.

Physiological Effect of Ghrelin on Body Systems.

Ghrelin is a relatively novel multifaceted hormone that has been found to exert a plethora of physiological effects. In this review, we found/confirmed that ghrelin has effect on all body systems. It induces appetite; promotes the use of carbohydrates as a source of fuel while sparing fat; inhibits lipid oxidation and promotes lipogenesis; stimulates the gastric acid secretion and motility; improves cardiac performance; decreases blood pressure; and protects the kidneys, heart, and brain. Ghrelin is important for learning, memory, cognition, reward, sleep, taste sensation, olfaction, and sniffing. It has sympatholytic, analgesic, antimicrobial, antifibrotic, and osteogenic effects. Moreover, ghrelin makes the skeletal muscle more excitable and stimulates its regeneration following injury; delays puberty; promotes fetal lung development; decreases thyroid hormone and testosterone; stimulates release of growth hormone, prolactin, glucagon, adrenocorticotropic hormone, cortisol, vasopressin, and oxytocin; inhibits insulin release; and promotes wound healing. Ghrelin protects the body by different mechanisms including inhibition of unwanted inflammation and induction of autophagy. Having a clear understanding of the ghrelin effect in each system has therapeutic implications. Future studies are necessary to elucidate the molecular mechanisms of ghrelin actions as well as its application as a GHSR agonist to treat most common diseases in each system without any paradoxical outcomes on the other systems.

Validation of in-house liquid direct agglutination test antigen: the potential diagnostic test in visceral Leishimaniasis endemic areas of Northwest Ethiopia.

BACKGROUND: Visceral leishmaniasis in Ethiopia is a re-emerging threat to public health, with increased geographical distribution and number of cases. It is a fatal disease without early diagnosis and treatment; thus, the availability of affordable diagnostic tools is crucial. However, due to delays caused by import regulations, procurement and late delivery of imported test kits, accessibility remains a problem in the control program. Therefore, we aimed to produce and evaluate the performance of an in-house liquid (AQ) direct agglutination test (DAT) antigen. RESULT: The AQ-DAT was produced at the Armauer Hansen Research Institute, using Leishmania donovani strain (MHOM/ET/67/L82). Sera from 272 participants; 110 microscopically confirmed cases of VL, 76 apparently healthy and 86 patients who had infectious disease other than VL were tested with AQ-DAT, and standard kits: Freeze-dried DAT (FD-DAT) and rK39. Taking microscopy as a gold standard; the sensitivity and specificity of the AQ-DAT were 97.3 and 98.8%, respectively. It had high degrees of agreement (k > 0.8), with a significant (P < 0.05) correlation compared to microscopy, FD-DAT, and rK39. CONCLUSION: Although further standardization is required, the in-house AQ-DAT could improve diagnostic accessibility, minimize intermittent stock outs and strengthen the national VL control program.

Caspase-1 as a regulatory molecule of lipid metabolism.

Caspase-1 is an evolutionarily conserved inflammatory mediated enzyme that cleaves and activates inflammatory cytokines. It can be activated through the assembly of inflammasome and its major effect is to activate the pro-inflammatory cytokines; interleukin 1ß (IL-1ß) and interluekine-18 (IL-18). In addition to IL-1ß and IL-8, several lines of evidence showed that caspase-1 targets the substrates that are involved in different metabolic pathways, including lipid metabolism. Caspase-1 regulates lipid metabolism through cytokine dependent or cytokine independent regulation of genes that involved in lipid metabolism and its regulation. To date, there are several reports on the role of caspase-1 in lipid metabolism. Therefore, this review is aimed to summarize the role of caspase-1 in lipid metabolism and its regulation.

Role Of Vitamin-D Supplementation In TB/HIV Co-Infected Patients.

OBJECTIVE: This review aimed to assess the role of vitamin D supplementation on the decrement of mortality and morbidity rate among tuberculosis (TB)/human immune deficiency virus (HIV) co-infected clients.Method: Pub Med, google scholar and google search were accessed to find out all document to describe this review article. RESULTS: Nowadays TB/HIV co-infection has become a major global concern, particularly in low and middle-income countries. Mycobacterium tuberculosis and HIV infections are co-endemic and more susceptible to the progression of TB. Immunosuppression associated with HIV is a strong risk factor for the reactivation of latent TB to the active form. Immune cells like macrophages recognized Mycobacterium tuberculosis through TLR2/1, and it increases the expression of the vitamin D receptor (VDR) and CYP27B1. The synthesis of 1,25-dihydroxy vitamin D promotes VDR-mediated transactivation of the antimicrobial peptide cathelicidin and the killing of intracellular Mycobacterium tuberculosis. Cathelicidins have a direct antimicrobial effect through membrane disruption. Besides, it has also antiviral effects via inhibition of retrovirus (HIV) replication. In fact, as some studies showed, there was a lower induction of cathelicidin in monocytes who have low vitamin D levels.Conclusion: Therefore, vitamin D supplementation can be directly involved in the reduction of TB/HIV co-infection and its progression.

TNF-α (-308) Gene Polymorphism and Type 2 Diabetes Mellitus in Ethiopian Diabetes Patients.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a metabolic disorder resulting from insulin insufficiency or function. Predisposing factors for T2DM are mainly genetic and environmental. Genetic polymorphism of cytokines like tumor necrosis factor-alpha (TNF-α) is suggestive of interference with insulin-sensitive glucose uptake and induces insulin resistance that ultimately could lead to T2DM. In this study, we assessed the effect of TNF-α (-308) G/A gene polymorphism and its association with the development of T2DM in an Ethiopian population. METHODS: An institutional-based cross-sectional study was conducted on study subjects with T2DM and non-diabetic healthy controls. DNA was extracted and genotyping was carried out by using amplification refractory mutation system polymerase chain reaction. A genetic-polymorphism on TNF-α (-308) G/A with T2DM was evaluated by logistic regression and Student's t-test. A P-value <0.05 was considered as statistically significant. RESULTS: In the present study, we observed a significant association between T2DM and TNF-α (-308) gene polymorphism's GG genotype [χ2 test P = 0.005, OR (95% CI) =2.667 (1.309-5.45d8)]. In contrast, no statistically significant differences were observed in the frequencies of genotypes AA and AG (χ2 test P=0.132 and 0.067, respectively). Moreover, T2DM individuals had higher concentrations of lipid profiles for those carrying the TNF-α (-308) GG genotype as compared to the control group. CONCLUSION: TNF-α (-308) genetic polymorphism may be implicated in the genetic susceptibility for, as well as the development of T2DM and lipid metabolism in the Ethiopian population. Therefore, a large-scale study and early screening of TNF-α (-308) genetic polymorphism may help in early management and control of diabetes and related outcomes.