An outbreak of new coronavirus (COVID-19) originated by SARS-CoV has reached 212 countries throughout the world. India is the second-highest populated country, so it is critical to forecasting the confirmed cases and deaths due to pandemic. To fulfil the purpose, three machine learning models Linear Regression, Multilayer Perceptron, and Sequential Minimal Optimization Regression are used. The predictive data of three geographic regions (India, Maharashtra, and Tamil Nadu) are compared with the data considered to be adequate in practice. The analysis concluded that Sequential Minimal Optimization Regression can be adopted for possible pandemic predictions such as COVID-19.
Background: Complicated intra-abdominal infections are still associated with a high risk of an unfavorable outcome. Despite the equal treatment, the mortality rates in some patients’ populations remain significant, especially when the impaired immune response is present. Aim: The object of this research is to analyze the impact of pro-inflammatory neutrophil CD64 and anti-inflammatory monocyte HLA-DR on the final outcome. Methods: We have searched in the PubMed database, the literature relating the prognostic value of two biomarkers - nCD64 and mHLA-DR in patients with complicated intra-abdominal infections and/or sepsis. Results: Eighteen original studies with 2960 patients fulfilled our inclusion criteria. The data about nCD64 that we found was contradictory, whereas low mHLA-DR expression showed good prognostic value. Conclusion : Our review showed heterogeneous data about nCD64 survival prediction. Further investigations with surgical patients exclusively are needed to evaluate its prognostic value in cIAIs. However, we observed a good prognostic performance of low mHLA-DR expression. After a validation in larger multicentre studies, mHLA-DR could be used as promising prognostic biomarker in cIAIs.
It is not unbeknownst to us that since the very onset of the COVID-19 outbreak, many patients from different age groups have suffered greatly, and in a remarkable number of cases, succumbed to their untimely demise as a result of infection with the novel coronavirus or SARS-CoV- -2. The elderly are perhaps the most vulnerable community, who stand at the pinnacle of morbidity and mortality rates due to contracting severe forms of COVID-19. Hopefully, based on the recent findings and the present evidence, there might be a number of medications that would possibly be of great prophylactic and therapeutic value to the elderly patients diagnosed with COVID-19. According to an interventional study, Thymosin α1 is arguably one such medication that has recently been indicated to be an effective therapeutic agent for inpatient management of lymphocytopenia and T cell exhaustion caused by COVID-19.
Background: Interleukin 10 (IL-10) is a powerful anti-inflammatory cytokine capable of preventing inflammatory and autoimmune diseases. Oral lichen planus (OLP) is an autoimmune, chronic, inflammatory disease with relapsing nature involving oral mucous membranes. It was prevsiouly assumed that like other autoimmune diseases, IL-10 may have a role in OLP pathogenesis, and many studies focused on that. But there are obvious controversies among IL-10 levels in OLP patients. Objective: In this review with Meta-Analysis, we attempt to assess IL-10 expression in OLP patients. Methods: The search was conducted via Pubmed, Ovid, and Google Scholar, to identify articles published up to Jun 2020. A meta-Analysis by Revman 5.3 was conducted based on serum levels of IL-10 in 313 OLPs and 203 controls. Results: With Meta-Analysis in 313 OLPs and 203 controls, the Mean difference between IL-10 in OLPs and controls was obtained as 0.26 (95% CI: -0.51-1.03), demonstrating no statistically significant difference. Conclusion: IL-10, in concert with its receptors, has a crucial role in the pathogenesis of various diseases, including inflammatory, infectious, and autoimmune diseases. Both over-expression, as well as IL-10 deficiency, have been described in oral lichen planus. With Meta-Analysis on serum IL-10 levels, it is speculated that no significant relationship exists between IL-10 and OLP pathogenesis. With respect to the importance of cytokines in the autoimmunity process, performing additional studies is of necessity to understand the association of other cytokines with OLP predisposition and its underlying pathological processes.
Interstitial lung disease, a term for a group of disorders, causes lung fibrosis, is mostly refractory to treatments and has a high death rate. After diagnosis the survival is up to 3 years but in some cases the patients live much longer. It involves a heterogenous group of lung diseases that exhibit progressive and irreversible destruction of the lung due to the formation of scars. This results in lung malfunction, disruption of gas exchange, and eventual death because of respiratory failure. The etiology of lung fibrosis is mostly unknown with a few exceptions. The major characteristics of the disease are comprised of injury of epithelial type II cells, increased apoptosis, chronic inflammation, monocytic and lymphocytic infiltration, accumulation of myofibroblasts, and inability to repair damaged tissue properly. These events result in abnormal collagen deposition and scarring. The inflammation process is mild, and the disease is primarily fibrotic driven. Immunosuppressants do not treat the disease but the evidence is evolving that both innate and acquired immune responses a well as the cytokines contribute to at least early progression of the disease. Furthermore, mediators of inflammation including cytokines are involved throughout the process of lung fibrosis. The diverse clinical outcome of the disease is due to different pattern of inflammatory markers. Nonetheless, the development of novel therapeutic strategies requires better understanding of the role of the immune response. This review highlights the role of the immune response in interstitial lung disease and considers the therapeutic strategies based on these observations. For this review several literature data sources were used to assess the role of the immune response in interstitial lung disease and to evaluate the possible therapeutic strategies for the disease.
The 2019 novel coronavirus (2019-nCoV) infection is an emerging pandemic that poses a severe threat to global public health. This pandemic started from the Wuhan City of Hubei Province in China, and is speculated to have originated from bats and spread among humans with an unknown intermediate transmitter. The virus binds to angiotensin-converting enzyme 2 (ACE2), which is abundantly expressed on various human cells, including lung epithelial and intestinal cells, thereby entering into these cells and causing infection. It is transmitted to other humans through airborne droplets from infected patients. Presently there are no specific treatments or vaccines that are available to curtail the spread of this disease. There are few indirect reports that explain the potential importance of the mandated BCG vaccine as a protective factor against COVID-19. There is a speculation that a live attenuated vaccine (BCG vaccine) can be beneficial against COVID-19 to develop the initial immune response, and can also spread in the community, thereby boosting herd immunity to fight against COVID-19. This review summarizes the conclusions of various reports on the BCG vaccine, and is an attempt to establish BCG-vaccination mediated herd immunity as an effective instant intermediate approach in curbing COVID-19 spread in highly populous countries.
Multiple sclerosis is a chronic inflammatory and demyelinating disorder of the central nervous system (CNS) that can cause cognition, mobility, and sensory impairments. Studies have shown that the immune system through inflammation and autoreactive T cells are involved in the progression of MS. The present article aimed to review the potent anti-inflammatory, antioxidant, and immunomodulatory agents that could modulate the immune response in MS. In herbal medicine, various medicinal plants including Olive, Silybum marianum, Grape, Pomegranate peel extract, Nigella sativa, Turmeric, Green tea, Aloysia citrodora, Boswellia papyrifera, Boswellia serrata, Ruta graveolens, and Andrographis paniculata are known with therapeutic benefits in MS patients through immunoregulation and reduction of major symptoms.
Background: Hemodialysis [HD] patients are more prone to blood-borne viruses, such as hepatitis B virus [HBV], hepatitis C virus [HCV], and, to a lesser extent, Human Immunodeficiency Virus [HIV]. Chronic HBV and HCV infections are associated with liver cirrhosis, hepatocellular carcinoma, and early graft failure after kidney transplantation. As there was no recent information, this study aimed to evaluate the prevalence of HBV, HCV, and HIV infection in HD patients in Fars province, southern Iran. This could help health policymakers to run more effective infection control practices for reducing such blood-borne virus infections, if necessary. Methods: This cross-sectional study was performed on 906 HD patients in Fars province, southern Iran. A total of 906 blood samples were obtained from patients and diagnostic tests of HBV, HCV, and HIV were done. Demographic data and some other information, such as duration of dialysis, were extracted from the patients’ medical records. Data were analyzed in SPSS, version 18. Results: Out of the patients enrolled in the study, 547 [60.4%] were male and 359 [39.6%] female. The mean ± SD age of the patients was 58.0 ± 15.8 years. The prevalence of HBV, HCV, and HIV infection was 0.88%, 0.55% and 0.44%, respectively. HIV-infected subjects were significantly younger than the HIV-negative group [P <0.017]. Conclusion: It seems that Fars is among the provinces with low HBV and HCV prevalence in HD patients in comparison to other provinces of Iran. On the other hand, HIV prevalence here is higher than other provincial studies. Strict adherence to preventive infection control measures is recommended in HD centers.
The prevalence of the major subgroup of A as A1 in almost 80% of the A group population is a known fact. A2 and the remaining subgroups such as Aend, Am, Ax etc comprise the remaining population, based on erythrocyte agglutinability and various serological reactions. These A subgroups can often result in an ABO typing discrepancy. Anti-A1 antibody often appears as an irregular cold agglutinin in the sera of A2 or A2B individuals who lack the corresponding antigen. Rather notably, the literature suggests that 1% to 8% of A2 and 22% to 35% of A2B individuals possess an allo-anti-A1 in their sera, which reacts at a temperature below 25°C. Although routinely, it does not pose any problem either during or post blood transfusion, however, the literature reports of hemolysis happening in procedures that are performed at lower temperatures, particularly in hypothermic situations. We report herein, a case of a massively bleeding A2B Indian lady after the expulsion of her dead fetus and an underlying uterine fibroid having a warm reactive allo-anti-A1 agglutinin that warranted an urgent blood transfusion management.
COVID-19 (Coronavirus disease) is the most contagious virus, which has been characterized as a global pandemic by WHO. The pathological cycle of COVID-19 virus can be specified as RNAaemia, severe pneumonia, along with the Ground-glass opacity (GGO), and acute cardiac injury. The S protein of Coronavirus has been reported to be involved in the entry of the virus into the host cell, which can be accomplished by direct membrane fusion between the virus and plasma membrane. In the endoplasmic reticulum or Golgi membrane, the newly formed enveloped glycoproteins are introduced. The spread of disease occurs due to contact and droplets unleashed by the vesicles holding the virus particles combined with the plasma membrane to the virus released by the host. The present manuscript describes the pathogenesis of COVID-19 and various treatment strategies that include drugs such as chloroquine and hydroxychloroquine, an anti-malarial drug, antibodies: SARS-CoV-specific human monoclonal antibody CR3022 and plasma treatment facilitate the therapeutic effect.
The transmission of HIV is generally inefficient. Despite the development of a diverse viral quasispecies in a chronically infected individual, a severe genetic bottleneck is observed during transmission, leading to only one or a few genetic variants establishing infection. This genetic bottleneck is the result of both stochastic events and selection pressures, such that viruses with specific traits are favored during transmission. This chapter discusses current models of HIV mucosal transmission, evidence for selection of specific viral traits during this process, and the biological characterization of transmitted founder viruses based on monkey models and human cohorts. The impact of transmitted viral phenotypes on disease progression is also described. Understanding in greater depth the key viral features required for transmission will be essential to the development of effective interventions for HIV prevention.
The protective function of mucosal HIV-1- or SIV-specific antibodies against viral infection has stimulated extensive studies of their Ig isotype association with differences in specificity and in effector functions. In contrast to many mucosally acquired microbial infections in which the humoral responses are dominated by induction of secretory IgA (S-IgA), HIV-1/SIV infections stimulate vigorous IgG responses in sera as well as in external secretions but low IgA virus-specific antibodies although the total levels of IgA in these fluids remain unaltered. The diminished or even absent IgA responses to HIV-1/SIV and to other mucosal antigens in external secretions and their replacement with IgG is likely to influence the functionality of mucosal barriers and eliminate antiinflammatory effector functions of IgA antibodies. Furthermore, the polymeric character of S-IgA with 4-8 antigen-binding sites, exquisite resistance to proteolysis and anti-inflammatory potential are of great advantage in mucosal protection. The markedly different effector functions of mucosal antibodies of IgG and IgA isotypes must be considered in the design of HIV-1 vaccines to stimulate S-IgA responses at sites of virus entry and IgG responses in the systemic compartment.
Background: Preterm Birth (PTB) is one of the main causes of neonatal death and infant mortality and morbidity. The pro-inflammatory cytokine interleukin-6 (IL-6) is a major proinflammatory mediator of the host response to infection and malondialdehyde (MDA) is a marker of oxidative stress. Objective : To evaluate potential associations between IL-6 and MDA levels in women with preterm birth. Method: A total of 150 women (66 with full-term and 84 with PTB) were enrolled in this case-control study. Predesigned performas were filled through questionnaire interviews to collect data on personal, demographic, occupational, lifestyle and reproductive history. Blood samples were collected within 36 hours of delivery. Serum concentrations of IL-6 and MDA were determined in mothers with full-term and preterm birth. Results: The mean age was marginally higher; whereas BMI was slightly lower in cases (PTB) as compared to controls (full-term) subjects. Serum IL-6 and MDA levels were significantly higher in subjects with PTB than full-term birth. The data were further analyzed with respect to underweight, normal and overweight/obese BMI. In all the BMI categories, the levels of IL-6 and MDA were higher in PTB cases. Among the PTB categories, the levels of IL-6 and MDA were highest in moderate to late preterm birth. A significant positive correlation was found between IL-6 and MDA levels. There was a weak negative correlation between either IL-6 or MDA and the number of gestational weeks. Conclusion : Elevated maternal serum levels of Interleukin-6 and Malondialdehyde in preterm as compared to full-term birth might suggest that inflammation and oxidative stress play a critical role in PTB.
Optimal protective immunity to HIV will likely require that plasma cells, memory B cells and memory T cells be stationed in mucosal tissues at portals of viral entry. Mucosal vaccine administration is more effective than parenteral vaccine delivery for this purpose. The challenge has been to achieve efficient vaccine uptake at mucosal surfaces, and to identify safe and effective adjuvants, especially for mucosally administered HIV envelope protein immunogens. Here, we discuss strategies used to deliver potential HIV vaccine candidates in the intestine, respiratory tract, and male and female genital tract of humans and nonhuman primates. We also review mucosal adjuvants, including Toll-like receptor agonists, which may adjuvant both mucosal humoral and cellular immune responses to HIV protein immunogens.
Increased availability of antiretroviral therapy to pregnant and breastfeeding women in resource-limited areas has proven remarkably successful at reducing HIV vertical transmission rates over the past several decades. Yet, still more than 170,000 children are infected annually due to failures in therapy implementation, monitoring, and adherence. Mother-to-child transmission (MTCT) of HIV-1 can occur at one of several distinct stages of infant development - intrauterine, intrapartum, and postpartum. The heterogeneity of the maternal-fetal interface at each of these modes of transmission poses a challenge for the implementation of immune interventions to prevent all modes of HIV MTCT. However, using mother-infant human cohorts and nonhuman primate models of infant simian immunodeficiency virus (SIV) acquisition, investigators have made important observation about the biology of pediatric HIV infection and have identified unique protective immune factors for each mode of transmission. Knowledge of immune factors protective against HIV MTCT will be critical to the development of targeted immune therapies to prevent infant HIV acquisition and to bring an end to the pediatric AIDS epidemic.
HIV-1 is present in many secretions including oral, intestinal, genital, and breast milk. However, most people exposed to HIV-1 within these mucosal compartments do not become infected despite often frequent and repetitive exposure over prolonged periods of time. In this review, we discuss what is known about the levels of cell-free HIV RNA, cell-associated HIV DNA and cell-associated HIV RNA in external secretions. Levels of virus are usually lower than contemporaneously obtained blood, increased in settings of inflammation and infection, and decreased in response to antiretroviral therapy. Additionally, each mucosal compartment has unique innate and adaptive immune responses that affect the composition and presence of HIV-1 within each external secretion. We discuss the current state of knowledge about the types and amounts of virus present in the various excretions, touch on innate and adaptive immune responses as they affect viral levels, and highlight important areas for further study.
Current epidemiological data convincingly indicate that HIV infection is acquired predominantly by the mucosal route, analogous with the majority of infectious diseases [1]. Mucosal surfaces of the genital and intestinal tracts are the major sites of virus entry, yet major discoveries and advances in the technologies in the last decade alone have reinforced the importance of examining mucosal immune responses. The earliest and most profound alterations of the immune system occur in mucosal tissues of the intestinal tract, which constitute a crucial step in the pathogenesis of HIV [2, 3]. Furthermore, untreated HIV patients are also usually infected by opportunistic mucosal pathogens of viral, bacterial, fungal and parasitic origin. The marked quantitative and qualitative differences of the mucosal and systemic compartments of the immune system comprise the dominant mucosal site of exposure to environmental antigens; phenotypically distinct cell populations including the antigen-presenting dendritic cells, macrophages, epithelial cells, T and B lymphocytes, innate lymphoid cells, plasma cells; production and selective transport of antibodies; and unique innate factors of immunity present in mucosal tissues and secretions. In particular, HIV exploits the unique aspects of the mucosal immune system, especially its reservoir of activated CD4+ T target cells, which support viral infection, amplification, mutation, and destruction of key immunoregulatory cells involved in mucosal immunity. Loss of mucosal barrier integrity permits translocation of foreign antigens into the systemic circulation resulting in further viral replication and continual seeding of viral reservoirs [3, 4]. Furthermore, the loss of immunoregulatory T cells in mucosal tissues contributes to the lack of normal immune suppression, leading to increased levels of inflammation supportive of continued HIV replication and persistence in tissues. Finally, mucosal tissues are increasingly recognized as the major reservoir for viral persistence in patients on antiretroviral therapy, especially in the Gut-Associated Lymphoid Tissues (GALT) of the lower intestinal tract.
Recent research has highlighted the growing public health concern arising from mismanagement of malarial and non-malarial febrile illnesses that present with similar clinical symptoms. A retrospective examination of patient records suggests that a syndrome-based diagnosis results in over-diagnosis of malaria. Consequently, interventions to mitigate the frequency of presumptive treatment of fever in malaria-endemic settings have been sought, especially for resourcelimited areas. Guidelines that promote the use of microbiological tests and modern diagnostic kits have demonstrated laudable progress in the ongoing challenge of febrile illness management. However, this has brought attention to other factors like the complication of mixed infections. These issues, which remain significant limitations to current tools and methods in the accurate diagnosis and subsequent therapy of febrile illnesses, call for innovative diagnostic interventions. Advancements in biomedical research over the last decade have led to the introduction of state-of-the-art molecular techniques of omics origin that provide the possibility of diverse applications in disease diagnostics. Here, we present notable challenges in febrile illness management, describe currently available tools and methods for diagnosis, and discuss the opportunities for future progress, including harnessing cuttingedge transcriptional profiling and proteomics technology to detect host immunological signatures during infection.
Cancer is the second leading cause of death and morbidity in the world among noncommunicable diseases after cardiovascular ailments. With the advancement in science and research, a number of therapies have been developed to treat cancer, including chemotherapy, radiotherapy and immunotherapy. Chemo and radiotherapy have been in use since the last two decades, however these are not devoid of their own intrinsic problems, such as myelotoxicity, cardiotoxicity, nephrotoxicity, neurotoxicity and immunosuppression. Hence, there is an urgent need to develop alternative methods for the treatment of cancer. An increase in the cases of various cancers has encouraged the researchers to discover novel, more effective drugs from plant sources. In this review, fifteen medicinal plants alongside their products with anticancer effects will be introduced and discussed, as well as the most important plant compounds responsible for the anticancer activity of the plant. Several phenolic and alkaloid compounds have been demonstrated to have anticancer effects on various types of cancers. The most fundamental and efficient role exhibited by these secondary plant metabolites against cancer involves removing free radicals and antioxidant effects, induction of apoptosis, cell cycle arrest and inhibition of angiogenesis. Moreover, recent studies have shown that plants and their metabolites may provide an alternative to the existing approaches, including chemotherapies and radiotherapies, in the treatment of cancer. In this review, a brief overview of important secondary metabolites having anticancer activity will be given, along with the major molecular mechanisms involved in the disease. In addition to this, recent advances in secondary metabolites from various medicinal plants in the prevention and treatment of cancer will be explored.
Macrophages are the phagocytic sentinel cells of our body, with high plasticity required to maintain homeostasis. This incredibly diverse set of cells, in response to various environmental stimuli such as cytokines and other factors, constantly alters their functional state/phenotype. They undergo polarization not only into conventional M1/M2 axis but also undergo a diverse spectrum of macrophage subtypes which play critical roles in various immune functions and homeostasis. In the tumor microenvironment, monocytes polarize along with the alternatively activated macrophages AAM or M2 macrophages associated with pro-tumoral features whereas M1 macrophages exert antitumor functions. Tumor-Associated Macrophage (TAM) infiltration has long been associated with poor prognosis and therefore represents potential diagnostic and prognostic biomarkers in solid tumors. Inhibiting the recruitment of monocytes into the tumor microenvironment and targeted deletion of TAMs have shown promising results. Targeting the TAMs towards M1-like macrophages has also demonstrated to be an efficient way to prevent tumor progression and metastasis. Here in this article, we review how TAMs orchestrate different steps in tumor progression and metastasis and the opportunities to target them in the quest for cancer prevention and treatment. Further, we explore how chemotherapies and immunotherapies can target TAM reprogramming and depletion to serve as a strategy for the control of various types of cancers in the future.
