Leishmaniasis, a neglected tropical disease, affects millions of people globally. Various chemotherapeutic interventions have been employed for its treatment; however, the emergence of resistance in parasites and the adverse side effects associated with these medications have necessitated the screening of traditionally significant medicinal plants. We have investigated the phytochemistry screening, characterization, and in vitro anti-leishmanial activity of Toona ciliata M. Roem leaf extract. Leaf metabolites were extracted using a Soxhlet system with ethyl acetate as an extraction solvent. The total phenolic and total flavonoid content were quantified using the Folin-Ciocalteu (FC) and aluminium chloride (AlCl3) methods, respectively. HPTLC, HRLC-MS, GC-MS, and FTIR analyses were conducted to ascertain the essential chemical composition and functional groups associated with phytoconstituents present in the extract. Leishmania inhibition assays were performed against both promastigote and amastigote forms, yielding IC50 values of 44.40 ± 5.53 µg ml-1 and 32.34 ± 1.89 µg ml-1 & 21.68 ± 0.59 µg ml-1 in J774A.1 and RAW264.7 cells respectively. Furthermore, to determine the extract's safety profile, a cytotoxicity assay conducted on cell lines such as J774A.1, RAW264.7 and THP-1, peripheral blood mononuclear cells, and erythrocytes indicated no toxicity. These findings established a foundation for further comprehensive research on Toona ciliata M. Roem, aiming to identify novel bioactive compounds exhibiting anti-leishmanial activity within the crude extract.

ABSTRACT Visceral leishmaniasis (VL) is a vector-borne disease caused by the obligate intracellular protozoan Leishmania donovani in India. VL can be complicated by post-kala-azar dermal leishmaniasis (PKDL), a macular or nodular rash that develops in 10%–20% of patients after treatment of VL in India. Patients with PKDL are infectious to sand flies, promoting further transmission of the parasite. MicroRNAs (miRNAs) are 18–25 nt, non-coding RNAs that simultaneously regulate the expression of several or many target transcripts. This study was based on the hypothesis that the host response to L. donovani is modified by distinct sets of miRNAs in VL or PKDL and that these might differ from healthy controls. We investigated this hypothesis using a NanoString panel to profile the miRNAs expressed in the plasma of patients with VL or PKDL diagnosed at a hospital in Bihar, India. We compared these to plasma microRNAs of healthy control individuals from the same endemic villages. miRNAs hsa-miR-223-3p, hsa-miR-191-5p, hsa-miR-23a-3p, and hsa-1285-5p were significantly higher in the plasma samples from patients with VL compared to either PKDL or endemic controls. Prediction programs highlighted potential mRNA targeted by these miRNAs, among which we verified the down-modulation of several transcripts belonging to the NFκB and NLRP3 inflammasome pathways in circulating leukocytes of VL patients. By contrast, miRNA patterns in subjects with PKDL were similar to control subjects, possibly suggesting that the pathogenic immune response during PKDL is primarily localized in the skin. IMPORTANCE Infection of humans with the protozoan Leishmania donovani can be asymptomatic or it can cause fatal visceral leishmaniasis (VL), sometimes followed by the cutaneous complication PKDL. Parasites are spread through sand fly bites in endemic regions, and parasites in post-kala-azar dermal leishmaniasis (PKDL) skin lesions are a source of prolonged parasite transmission to sand flies, compromising disease eradication efforts. Since microRNAs can simultaneously modify the expression of multiple genes, we examined microRNAs in the blood that might be partial determinants of pathogenic responses leading to VL or PKDL. Our studies revealed several miRNAs expressed that are elevated in the plasma of patients with VL, which suppress some of the inflammatory responses that promote parasite killing. However, miRNA profiles were very similar between PKDL patients and controls, raising the possibility that major factors that lead to prolonged retention of parasites in the skin during PKDL are not systemic but are localized in the skin.

Oral squamous cell carcinoma (OSCC) is a malignant neoplasm of the oral epithelium that constitutes majority of oral cancers and is strongly associated with risk factors such as tobacco use and genetic alterations. Mortality rates for OSCC are high because many cases are misdiagnosed or identified at later stages, and treatment options are limited with high recurrence. Therefore, there is an urgent need for improved diagnostic and therapeutic strategies. OSCC tumor cells, like those in other solid malignancies, exhibit significant alterations in metabolic pathways and the immune microenvironment. These changes can serve as valuable biomarkers for early detection and as targets for innovative treatment strategies. This review summarizes the current understanding of metabolic and immunological biomarkers that are either currently in use for OSCC or are in different phases of clinical trials.

Protozoan parasite infections, particularly leishmaniasis, present significant public health challenges in tropical and subtropical regions, affecting socio-economic status and growth. Despite advancements in immunology, effective vaccines remain vague, leaving drug treatments as the primary intervention. However, existing medications face limitations, such as toxicity and the rise of drug-resistant parasites. This presents an urgent need to identify new therapeutic targets for leishmaniasis treatment. Understanding the complex life cycle of Leishmania and its survival in host macrophages can provide insights into potential targets for intervention. Current treatments, including antimonials, amphotericin B, and miltefosine, are constrained by side effects, costs, resistance, and reduced efficacy. Exploring novel therapeutic targets within the parasite's physiology, such as key metabolic enzymes or essential surface proteins, may lead to the development of more effective and less toxic drugs. Additionally, innovative strategies like drug repurposing, combination therapies, and nanotechnology-based delivery systems could enhance efficacy and combat resistance, thus improving anti-leishmanial therapies.

Endophytes are a group of microbes residing mutually within the tissues of their host plant without causing any overt symptoms. Secondary metabolites produced by fungal endophytes are used in the treatment of many diseases including protozoan diseases like malaria and visceral leishmaniasis (also known as kala-azar). These two parasitic diseases together cause mortality and morbidity to millions of people globally. There are drugs available to treat these diseases, but the increasing resistance among the protozoan parasite to present-day drugs has driven the scientific community in search of novel sources of pharmacologically active compounds of therapeutic value, and medicinal plants derived from fungal endophytes have shown substantial potential for this cause. Compounds like Taxol, quinine, cytochalasins, cyclodepsipeptide, fusaripeptide A, cochlioquinone A, purpureone, isocochlioquinone A, citrinin, terrenolide S, and curvulin derived from fungal endophytes have been used for their anti-plasmodial and antileishmanial property, respectively. This book chapter reviews natural bioactive compounds derived from fungal endophytes with various antiparasitic biological activities.

Leishmaniasis, caused by obligate intracellular Leishmania parasites, poses a significant global health burden. The control of Leishmania infection relies on an effective T cell-dependent immune response; however, various factors impede the host’s ability to mount a successful defence. Alterations in the chemokine profile, responsible for cell trafficking to the infection site, can disrupt optimal immune responses and influence the outcome of pathogenesis by facilitating parasite persistence. This review aims to emphasize the significance of the chemokine system in T cell responses and to summarize the current knowledge on the dysregulation of chemokines and their receptors associated with different subsets of T lymphocytes during Leishmaniasis. A comprehensive understanding of the dynamic nature of the chemokine system during Leishmaniasis is crucial for the development of successful immunotherapeutic approaches.

Missing values in the Internet traffic data pose a serious challenge for use in several traffic engineering applications. Compressive sensing is a generic methodology for the reconstruction of missing values in the tensor representation of the data. Existing decomposition techniques for compressive sensing suffer from two limitations; need to know the tensor rank apriori and the usage of alternating least squares (ALS) procedure. To avoid these limitations, we propose tensor-CUR decomposition technique for compressive sensing based on statistical leverage score for selection of frontal slices and tubes of traffic tensor, that in turn give a relative-error bound on reconstruction. We establish that the proposed relative-error bound tensor-CUR (TCUR-REB) decomposition technique is better than the known additive-error bound tensor-CUR (TCUR-AEB) decomposition. Application of the TCUR-REB to the reconstruction of missing values in Internet traffic tensor using two public datasets shows that it has the smallest computational time. The proposed decomposition method also shows the smallest error in the reconstruction of missing values compared to the other tensor decomposition methods.

Leishmaniasis is a group of diseases that predominantly affect impoverished individuals in developing regions. Recent research has highlighted the significant role of microRNAs (miRNAs), small noncoding RNA molecules, in regulating gene expression and contributing to disease pathogenesis in leishmaniasis. Understanding the intricate miRNA-mediated interactions provides valuable insights into the underlying mechanisms of leishmaniasis and facilitates the development of targeted interventions. Moreover, miRNAs demonstrate altered expression levels, and their presence in the bloodstream enables noninvasive detection, making them promising biomarker candidates for diagnosis and prognosis. This chapter focuses on the role of miRNAs in regulating the immune response during leishmania infection, emphasizing their potential as both biomarkers and therapeutic targets.

BACKGROUND:Post kala-azar dermal leishmaniasis (PKDL) is a consequential dermal manifestation of visceral leishmaniasis (VL), serving as a parasite reservoir. The traditional diagnostic approach, which requires an invasive skin biopsy is associated with inherent risks and necessitates skilled healthcare practitioners in sterile settings. There is a critical need for a rapid, less invasive method for Leishmania detection. The main objective of this study was to evaluate and compare the diagnostic efficacy of PCR and qPCR in detecting PKDL, utilizing both skin and blood samples and to assess the utility of blood samples for molecular diagnosis.METHODS AND RESULTS:73 individuals exhibiting clinical symptoms of PKDL and who had tested positive for rK39 rapid diagnostic test (RDT) were enrolled in this study. For the diagnosis of PKDL, both PCR and real-time quantitative PCR (qPCR), employing SYBR Green and TaqMan assays, were performed on blood and skin matched samples. qPCR results using both TaqMan and SYBR Green assay, indicated higher parasite loads in the skin compared to blood, as evident by the Ct values. Importantly, when blood samples were used for PKDL diagnosis by qPCR, an encouraging sensitivity of 69.35% (TaqMan assay) and 79.36% (SYBR Green) were obtained, compared to 8.2% with conventional PCR.CONCLUSION:The findings of the study suggest the potential utility of blood for molecular diagnosis by qPCR, offering a less invasive alternative to skin biopsies in field setting for the early detection of parasitaemia in PKDL patients and effective management and control of the disease.

Major histocompatibility complex (MHC) tetramers stand as formidable tools within T cell biology, facilitating the exploration and comprehension of immune responses. These artificial molecules, comprising four bound MHC molecules, typically with a specified peptide and a fluorescent label, play a pivotal role in characterizing T cell subsets, monitoring clonal expansion, and unraveling T cell dynamics during responses to infections or immunotherapies. Beyond their applications in T cell biology, MHC tetramers prove valuable in investigating a spectrum of diseases such as infectious diseases, autoimmune disorders, and cancers. Their instrumental role extends to vaccine research and development. Notably, when appropriately configured, tetramers transcend T cell biology research and find utility in exploring natural killer T cells and contributing to specific T cell clonal deletions.

Understanding the development and maintenance of immunological memory is important for efforts to eliminate parasitic diseases like leishmaniasis. Leishmaniasis encompasses a range of pathologies, resulting from infection with protozoan parasites belonging to the subgenera Leishmania and Viannia of the genus Leishmania. A striking feature of these infections is that natural or drug-mediated cure of infection generally confers life-long protection against disease. The generation of protective T cell responses are necessary to control Leishmania infections. CD4+ T helper (Th) cells orchestrate immune responses in leishmaniasis and IFNγ+ Tbet+ CD4+ T (Th1) cells are required for the activation of phagocytes to kill captured or resident parasites, while other Th cell subset, including FoxP3+ natural regulatory T cells and Th2 cells can promote disease progression by suppressing the activities of Th1 cells. Upon resolution of a primary Leishmania infection, different subsets of CD4+ T cells, including tissue-resident memory T cells, effector memory T cells, central memory T cells, and short-lived effector T cells, help to confer resistance against reinfection. To maintain long-term protective Leishmania-specific CD4+ T cells responses, it is believed that persistent parasites or re-exposure to parasites at regular intervals is required (concomitant immunity). Despite the advances in our understanding about the immune responses during leishmaniasis, the generation of long-lasting protective immunity via vaccination has yet to be achieved. In this review, we summarize our current understanding about the formation and maintenance of immunological memory and control of leishmaniasis at the individual and population level. We will focus on Indian visceral leishmaniasis and discuss T cell responses that contribute to susceptibility to leishmaniasis, parasite persistence in populations and the environment, as well as describing advances in the development of leishmaniasis vaccines aimed at inducing protective CD4+ T cell responses.

Parasitic infections are a major global health issue causing significant mortality and morbidity. Despite substantial advances in the diagnostics and treatment of these diseases, the currently available options fall far short of expectations. From diagnosis and treatment to prevention and control, nanotechnology-based techniques show promise as an alternative approach. Nanoparticles can be designed with specific properties to target parasites and deliver antiparasitic medications and vaccines. Nanoparticles such as liposomes, nanosuspensions, polymer-based nanoparticles, and solid lipid nanoparticles have been shown to overcome limitations such as limited bioavailability, poor cellular permeability, nonspecific distribution, and rapid drug elimination from the body. These nanoparticles also serve as nanobiosensors for the early detection and treatment of these diseases. This review aims to summarize the potential applications of nanoparticles in the prevention, diagnosis, and treatment of parasitic diseases such as leishmaniasis, malaria, and trypanosomiasis. It also discusses the advantages and disadvantages of these applications and their market values and highlights the need for further research in this field.

Control of visceral leishmaniasis (VL) depends on proinflammatory Th1 cells that activate infected tissue macrophages to kill resident intracellular parasites. However, proinflammatory cytokines produced by Th1 cells can damage tissues and require tight regulation. Th1 cell IL-10 production is an important cell-autologous mechanism to prevent such damage. However, IL-10-producing Th1 (type 1 regulatory; Tr1) cells can also delay control of parasites and the generation of immunity following drug treatment or vaccination. To identify molecules to target in order to alter the balance between Th1 and Tr1 cells for improved antiparasitic immunity, we compared the molecular and phenotypic profiles of Th1 and Tr1 cells in experimental VL caused by Leishmania donovani infection of C57BL/6J mice. We also identified a shared Tr1 cell protozoan signature by comparing the transcriptional profiles of Tr1 cells from mice with experimental VL and malaria. We identified LAG3 as an important coinhibitory receptor in patients with VL and experimental VL, and we reveal tissue-specific heterogeneity of coinhibitory receptor expression by Tr1 cells. We also discovered a role for the transcription factor Pbx1 in suppressing CD4+ T cell cytokine production. This work provides insights into the development and function of CD4+ T cells during protozoan parasitic infections and identifies key immunoregulatory molecules.

BackgroundIt has been amply described that levels of IgM antibodies against Mycobacterium leprae (M. leprae) phenolic glycolipid I (PGL-I) correlate strongly with the bacterial load in an infected individual. These findings have generated the concept of using seropositivity for antibodies against M. leprae PGL-I as an indicator of the proportion of the population that has been infected. Although anti-PGL-I IgM levels provide information on whether an individual has ever been infected, their presence cannot discriminate between recent and past infections. Since infection in (young) children by definition indicates recent transmission, we piloted the feasibility of assessment of anti-PGL-I IgM seroprevalence among children in a leprosy endemic area in India as a proxy for recent M. leprae transmission.Material and methodsA serosurvey for anti-PGL-I IgM antibodies among children in highly leprosy endemic villages in Bihar, India, was performed, applying the quantitative anti-PGL-I UCP-LFA cassette combined with low-invasive, small-volume fingerstick blood (FSB).ResultsLocal staff obtained FSB of 1,857 children (age 3–11 years) living in 12 leprosy endemic villages in Bihar; of these, 215 children (11.58%) were seropositive for anti-PGL-I IgM.ConclusionThe anti-PGL-I seroprevalence level of 11.58% among children corresponds with the seroprevalence levels described in studies in other leprosy endemic areas over the past decades where no prophylactic interventions have taken place. The anti-PGL-I UCP-LFA was found to be a low-complexity tool that could be practically combined with serosurveys and was well-accepted by both healthcare staff and the population. On route to leprosy elimination, quantitative anti-PGL-I serology in young children holds promise as a strategy to monitor recent M. leprae transmission in an area.

Malaria, caused by Plasmodium species, remains a major global health concern, causing millions of deaths annually. While the introduction of the RTS,S vaccine has shown promise, there is a pressing need for more effective vaccines due to the emergence of drug-resistant parasites and insecticide-resistant vectors. However, the complex life cycle and genetic diversity of the parasite, technical obstacles, limited funding, and the impact of the 2019 pandemic have hindered progress in malaria vaccine development. This review focuses on advancements in malaria vaccine development, particularly the ongoing clinical trials targeting antigens from different stages of the Plasmodium life cycle. Additionally, we discuss the rationale, strategies, and challenges associated with vaccine design, aiming to enhance the immune response and protective efficacy of vaccine candidates. A cost-effective and multistage vaccine could hold the key to controlling and eradicating malaria.

Visceral leishmaniasis (VL) is a severe and often fatal form of leishmaniasis caused by Leishmania donovani in the Indian sub-continent. Post Kala-azar Dermal Leishmaniasis (PKDL) is a late cutaneous manifestation of VL, typically occurring after apparent cure of VL, but sometimes even without a prior history of VL in India. PKDL serves as a significant yet neglected reservoir of infection and plays a crucial role in the transmission of the disease, posing a serious threat to the VL elimination program in the Indian sub-continent. Therefore, the eradication of PKDL should be a priority within the current VL elimination program aimed at achieving a goal of less than 1 case per 10,000 in the population at the district or sub-district levels of VL endemic areas. To accomplish this, a comprehensive understanding of the pathogenesis of PKDL is essential, as well as developing strategies for disease management. This review provides an overview of the current status of diagnosis and treatment options for PKDL, highlighting our current knowledge of the immune responses underlying disease development and progression. Additionally, the review discusses the impact of PKDL on elimination programs and propose strategies to overcome this challenge and achieve the goal of elimination. By addressing the diagnostic and therapeutic gaps, optimizing surveillance and control measures, and implementing effective intervention strategies, it is possible to mitigate the burden of PKDL and facilitate the successful elimination of VL in the Indian sub-continent.

γδ T cells are thymus derived heterogeneous and unconventional T- lymphocyte expressing TCR γ (V γ9) and TCRδ (Vδ2) chain and play an important role in connecting innate and adaptive armaments of immune response. These cells can recognize wide ranges of antigens even without involvement of major histocompatibility complex and exert their biological functions by cytotoxicity or activating various types of immune cells. In recent past, γδ T cells have emerged as an important player during protozoa infection and rapidly expand after exposure with them. They have also been widely studied in vaccine induced immune response against many bacterial and protozoan infections with improved clinical outcome. In this review, we will discuss the various roles of γδ T cells in immunity against malaria and leishmaniasis, the two important protozoan diseases causing significant mortality and morbidity throughout the world.

Optical computing is on its high demand in current years due to the expeditious advancements that made in optical algorithms and the construction of optical circuit design. The logic design of Boolean functions of optical circuits becomes a hectic job for the researchers. They introduce various approaches to synthesize the logical function by implementing different optical devices like MZI, TOAD and crossbar gates. This paper provides a blueprint about the advancement that has been performed by the researchers on this domain.