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Abstract Here in this study, a novel ternary CuS/HKUST‒1/Ni(acac)2 nano photocatalyst (CSHK‒Ni) was developed through a facile modification of HKUST‒1 MOF with Ni(acac)2 metal complex and by immobilizing CuS into the metal-organic framework (MOF). The incorporation of CuS, a narrow bandgap semiconductor, is anticipated to allow easy excitation by visible-light and improve the photocatalytic potential of the formulated catalyst which is validated by the decrease in the bandgap energy from 3.10 eV of pristine MOF to 2.19 eV. Moreover, the anchoring of the metal complex improves the light harvesting behavior by increased conjugation. Photoluminescence studies provided evidence of the effective separation of the photoinduced charge-carriers, reducing the rate of recombination and enhancing the photocatalytic potential of the CSHK‒Ni nanocomposite. The engineered catalyst displayed remarkable efficiency in the degradation of nitroimidazole containing antibiotics, Tinidazole (TNZ) and Metronidazole (MTZ), via H2O2 assisted AOP achieving a maximum photocatalytic efficiency of 95.87 ± 1.64% and 97.95 ± 1.33% in just 30 min under irradiation of visible light at optimum reaction conditions. The possible degradation pathway was elucidated based on the identification of ROS and degradation intermediates via HR‒LCMS and quenching experiments. Meanwhile, the chemical oxygen demand (COD) and total organic carbon (TOC) removal were also examined, encompassing the discussing of various aspects including reaction conditions, influence of various oxidizing agents, competing species and dissolved organic substrates present in the wastewater, marking the novelty of the study. This research elucidated the role of the CSHK‒Ni nanocomposite as an interesting photocatalyst in the elimination of emerging nitroimidazole containing pharmaceutical pollutant under visible-light exposure, presenting an exciting novel avenue for a cleaner and greener environment in the days to come.

Water borne emerging pollutants represents a significant challenge confronting the modern society. As a result of excessive use of dyes and pigments by the textile and other industries, substantial amount of these toxic and recalcitrant substances are widely dispersed into the aquatic sources that may raise serious health issues to all life forms besides causing potential disruption to the ecosystem. Treatments of these hazardous and non-biodegradable organic contaminants in wastewater effluents have become a focal point for researchers dedicated to environmental remediation. Notably, Metal organic frameworks (MOFs) and their composites have been reported to be promising materials for tackling such challenges. This review is dedicated to provide a concise overview by consolidating the diverse beneficial attributes of Cu-BTC MOF rendering it as a versatile material with applications spanning diverse domains, focusing on the reactivity, the role of the metal ion and its recent potential for addressing the elimination of toxic textile dye wastes from the wastewater effluent. Furthermore, it also documents the underlying mechanistic pathway governing the degradation mechanism and the superior electron transport property of Cu ̶ BTC, besides painting in detail the existing limitations that hinder their applicability at an industrial platform. Moreover, a set of future research outlooks serving as a roadmap for exploring the potentiality of Cu ̶ BTC MOFs have also been presented.

Background: Type 1 diabetes (T1D) is an autoimmune disease characterized by the specific destruction of insulin-producing beta cells in the pancreas by the immune system, including CD4 cells which orchestrate the attack and CD8 cells which directly destroy the beta cells, resulting in the loss of glucose homeostasis. Scope of review: This comprehensive document delves into the complex interplay between the immune system and beta cells, aiming to shed light on the mechanisms driving their destruction in T1D. Insights into the genetic predisposition, environmental triggers, and autoimmune responses provide a foundation for understanding the autoimmune attack on beta cells. From the role of viral infections as potential triggers to the inflammatory response of beta cells, an intricate puzzle starts to unfold. This exploration highlights the importance of beta cells in breaking immune tolerance and the factors contributing to their targeted destruction. Furthermore, it examines the potential role of autophagy and the impact of cytokine signaling on beta cell function and survival. Major conclusions: This review collectively represents current research findings on T1D which offers valuable perspectives on novel therapeutic approaches for preserving beta cell mass, restoring immune tolerance, and ultimately preventing or halting the progression of T1D. By unraveling the complex dynamics between the immune system and beta cells, we inch closer to a comprehensive understanding of T1D pathogenesis, paving the way for more effective treatments and ultimately a cure.

Introduction: Increased demand of service 24 hours around the clock has divided the workers into 2 domains as “Fixed duty” and “Shift duty”. Personals associated with shift duty are increasing in numbers day by day. Shift duty or more specifically night duty is associated with increased stress which results in high morbidity and decrease in work efficiency. Cortisol hormone and Heart Rate Variability (HRV) are useful parameters to determine the effects of stress. Aim: To find any change in cortisol levels, HRV, Athens score among the fixed duty and shift duty healthcare providers. Materials and Methods: A descriptive cross-sectional comparative study was conducted in a tertiary care hospital at Kolkata between July, 15th to Sept, 15th 2021. Predesigned and pretested questionnaire was made and ethical clearance was taken from institutional IEC. Then after taking consent total 120 (60 fixed duty and 60 shift duty) healthcare providers were recruited for the study. Subjects of the study filled up a questionnaire {including Athens Insomnia Scale (AIS)}. After applying exclusion criteria (any cardiovascular, neurological, psychological, sleep disorder) 120 health individuals were taken five minutes short-term HRV (time and frequency domain) recording in supine posture and 4 PM blood sample (for cortisol) were obtained from the participants which was further analysed in Chemiluminescence Immunoassay (CLI). Data was analysed in SPSS version 20.0. Statistical tests like student t-test, Cron bach’s alpha and chi-square tests were applied significant p6) than fixed duty workers. Blood test showed that shift duty workers had significantly high evening cortisol level than fixed duty workers (p= 0.036). The time domain of HRV showed that the parameters like Standard Deviation all NN interval (SDNN) (p=0.001), Mean HR (p=0.037), RMSSD (p

Networks of quantum devices with coherent control over their configuration offer promising advantages in quantum information processing, including quantum communication, computation, and sensing. So far, the investigation of these advantages assumed that the control system was initially uncorrelated with the data processed by the network. Here, we explore the power of quantum correlations between data and control, showing two communication tasks that can be accomplished with information-erasing channels if and only if the sender shares prior entanglement with a third party (the “controller”) controlling the network configuration. The first task is to transmit classical messages without leaking information to the controller. The second task is to establish bipartite entanglement with a receiver, or, more generally, to establish multipartite entanglement with a number of spatially separated receivers.

Mast cells (MCs) are tissue resident immune cells that play important roles in the pathogenesis of allergic disorders. These responses are mediated via the cross-linking of cell surface high affinity IgE receptor (FcϵRI) by antigen resulting in calcium (Ca2+) mobilization, followed by degranulation and release of proinflammatory mediators. In addition to FcϵRI, cutaneous MCs express Mas-related G protein-coupled receptor X2 (MRGPRX2; mouse ortholog MrgprB2). Activation of MRGPRX2/B2 by the neuropeptide substance P (SP) is implicated in neurogenic inflammation, chronic urticaria, mastocytosis and atopic dermatitis. Although Ca2+ entry is required for MRGPRX2/B2-mediated MC responses, the possibility that calcium release-activated calcium (CRAC/Orai) channels participate in these responses has not been tested. Lentiviral shRNA-mediated silencing of Orai1, Orai2 or Orai3 in a human MC line (LAD2 cells) resulted in partial inhibition of SP-induced Ca2+ mobilization, degranulation and cytokine/chemokine generation (TNF-α, IL-8, and CCL-3). Synta66, which blocks homo and hetero-dimerization of Orai channels, caused a more robust inhibition of SP-induced responses than knockdown of individual Orai channels. Synta66 also blocked SP-induced extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt phosphorylation and abrogated cytokine/chemokine production. It also inhibited SP-induced Ca2+ mobilization and degranulation in primary human skin MCs and mouse peritoneal MCs. Furthermore, Synta66 attenuated both SP-induced cutaneous vascular permeability and leukocyte recruitment in mouse peritoneum. These findings demonstrate that Orai channels contribute to MRGPRX2/B2-mediated MC activation and suggest that their inhibition could provide a novel approach for the modulation of SP-induced MC/MRGPRX2-mediated disorders.

Abstract Background Paramphistomosis is a pathogenic disease of domesticated ruminants, causing great economic loss in dairy industry and meat production. It is considered as a neglected tropical disease with highest prevalence throughout tropical and subtropical regions, particularly in Africa, Asia, Europe, and Australia. There are few trematocidal drugs available in the market. Most are resistant and have elevated side effects. Therefore, alternative trematocidal drugs need to discover. This study was conducted to evaluate three plants leaf extracts (from Senna alata, S. alexandrina, and S. occidentalis) as effective remedies against gastrointestinal trematode parasite (Paramphistomum gracile) of ruminants. Live adult parasites were collected in 0.1 M phosphate-buffered saline (PBS) from fresh autopsied goat’s rumen. Parasites were incubated in leaf extracts of S. alata, S. alexandrina and, S. occidentalis individually and in combination (1:1) ratio at 37 ± 1°C. Treatment media contain extracts at different concentrations (10, 20 and 40 mg/mL) in 10 mL of 0.1 M PBS with 1% dimethylsulphoxide (DMSO). Parasites in control group were incubated in PBS without extract. The efficacy of three Senna extracts was evaluated on the basis of dose-dependent motility and mortality of the trematode. Immediately after paralysis, all treated parasites were collected for histology, SEM and biochemical study. Results Dose-dependent efficacy was observed in terms of motility and time of mortality in all treated parasites after exposure in various concentrations of the Senna plant extracts. S. occidentalis and S. alexandrina showed better efficacy in combination than comparing with individual treatment groups. Histological study and scanning electron microscopic observations revealed conspicuous deformity of surface architecture in all treated parasites. Scanning electron micrographs also revealed shrinkage, vacuolization, infoldings and blebbings on the body surface of treated worms. Activities of tegumental enzymes were inhibited in all treatment groups compared to control. Conclusion The overall findings from this study revealed that all three Senna leaf extracts individually and in combination showed potential antitrematocidal activity against Paramphistomum gracile by damaging body tegument and neural propagation. Thus, this study confirmed that all three Senna extracts can be considered as a potential drug-like candidate in indigenous system of traditional medicine against trematode infections in livestock. Graphical abstract

Abstract Hemokinin-1 (HK-1) is a novel neuropeptide produced by human bronchial cells and macrophages and causes contraction of human bronchi ex vivo. It is also generated by antigen/IgE-activated murine mast cells (MCs) and contributes to experimental chronic allergic airway inflammation via the activation of the neurokinin receptor-1 (NK-1R) expressed on murine MCs. We found elevated MC numbers in the lungs of individuals who died from asthma (asthma) when compared to lungs of individuals who died from other causes (non-asthma). Mas-related G Protein coupled receptor X2 (MRGPRX2) is a novel G-protein coupled receptor (GPCR) that is expressed predominantly on human MCs. We detected low level of MRGPRX2 in non-asthma lung MCs but its expression was significantly upregulated in asthma lung MCs. HK-1 caused degranulation in a human MC line (LAD2) and RBL-2H3 cells stably expressing MRGPRX2 and this response was resistant to inhibition by an NK-1R antagonist. However, knockdown of MRGPRX2 in LAD2 cells resulted in substantial inhibition of HK-1-induced degranulation. These findings suggest that while HK-1 contributes to the development of experimental asthma in mice via NK-1R on murine MCs the effect of this neuropeptide on human bronchoconstriction likely reflects the activation of MRGPRX2 on lung MCs. Thus, development of selective MRGPRX2 antagonists could serve as novel target for the modulation of asthma.

Abstract Earlier we have established a carbazole alkaloid (mahanine) isolated from an Indian edible medicinal plant as an anticancer agent with minimal effect on normal cells. Here we report for the first time that mahanine-treated drug resistant and sensitive virulent Leishmania donovani promastigotes underwent apoptosis through phosphatidylserine externalization, DNA fragmentation and cell cycle arrest. An early induction of reactive oxygen species (ROS) suggests that the mahanine-induced apoptosis was mediated by oxidative stress. Additionally, mahanine-treated Leishmania-infected macrophages exhibited anti-amastigote activity by nitric oxide (NO)/ROS generation along with suppression of uncoupling protein 2 and Th1-biased cytokines response through modulating STAT pathway. Moreover, we have demonstrated the interaction of a few antioxidant enzymes present in parasite with mahanine through molecular modeling. Reduced genetic and protein level expression of one such enzyme namely ascorbate peroxidase was also observed in mahanine-treated promastigotes. Furthermore, oral administration of mahanine in acute murine model exhibited almost complete reduction of parasite burden, upregulation of NO/iNOS/ROS/IL-12 and T cell proliferation. Taken together, we have established a new function of mahanine as a potent antileishmanial molecule, capable of inducing ROS and exploit antioxidant enzymes in parasite along with modulation of host’s immune response which could be developed as an inexpensive and nontoxic therapeutics either alone or in combination.

Context: Clerodendrum viscosum Vent. (Verbenaceae) is a shrub, widely used amongst the natives of India against various diseases. Objective: Crude extract of the plant was tested in vitro on a tapeworm Raillietina tetragona Molin (Davaineidae) to evaluate its potential anthelmintic efficacy and ultrastructural changes in the parasite. Materials and methods: Parasites were exposed to different concentrations of ethanolic leaf extract (10–80 mg/mL) and praziquantel (0.0005–0.005 mg/mL) and incubated in phosphate-buffered saline (PBS). The pH was 7.4 at 37 °C, while one set of worms was incubated only with PBS as a control. Permanent immobilization of worms was determined visually when no motility occurred on physically disturbing them. The parasites exposed to high concentrations of leaf extract and praziquantel treatments were processed for histological and electron microscopic studies, as these concentrations took the least time for paralysis and death to occur. Result: With an increase in the concentration of the leaf extract from 10 to 80 mg/mL and praziquantel from 0.0005 to 0.005 mg/mL, the time for the onset of paralysis and death was shortened. The treated parasites lost their spontaneous movement rapidly followed by death. Electron microscopic observations revealed disruptions in the tegument and parenchymal layer, accompanied by deformities in cell organelles. Discussion and conclusion: Extensive structural alterations in the tegument indicate that the plant-derived components cause permeability changes in the parasite leading to paralysis and subsequent death. These observations suggest that phytochemicals present in C. viscosum have vermifugal or vermicidal activity, and thus may be exploited as alternative chemotherapeutic agents.

Altered sialylation is generally maintained by a fine balance between sialidases and sialyltransferases, which plays an essential role during disease pathogenesis. TLR4 is a membrane-bound highly sialylated glycoprotein predominantly having α2,3-linked sialic acids. It is one of the most important client molecules in the anti-leishmanial innate immune arm. Here, we initiated a comprehensive study on the modulation of TLR4 sialylation in Leishmania donovani (L. d)-infected macrophages by a mammalian sialidase/neuraminidase-1 (Neu1) having substrate specificity toward α2,3-linked sialic acids. We observed reduced membrane-associated Neu1 with its decreased enzyme activity in infected macrophages. Moreover, we demonstrated reduced association of Neu1 with TLR4 leading to enhanced sialylation of TLR4 in these infected cells. Conversely, Neu1 over expression exhibited enhanced association of TLR4 with Neu1 leading to reduced sialylation which possibly linked to increased association of TLR4 with its downstream adaptor protein, MyD88. This, in turn, activated downstream MAP kinase signaling pathway, with enhanced nuclear translocation of NFκB that resulted in increased genetic and protein levels expression of Th1 cytokines and effector molecule nitric oxide secretion which ultimately leads to reduced parasite burden in macrophages. This was further validated by Neu1 silencing in infected macrophages which reversed such a situation. Such events strongly confirm the importance of Neu1 in modulation of TLR4 sialylation during parasite infection resulting in impairment of innate immune response. Furthermore, decreased membrane-bound Neu1 in infected macrophages could be attributed to its reduced tyrosine-phosphorylation as well as diminished association with cathepsin A. Both these phenomenon possibly play significant roles in inhibiting translocation of the sialidase from cytosol to membrane. Taken together, our study first time demonstrated impaired translocation of cytosolic Neu1 to the membrane of L. donovani-infected macrophages due to impaired phosphorylation of this enzyme. This novel finding establishes a link between enhanced α2,3-linked sialic acids on TLR4 and reduced membrane-bound Neu1 which plays a significant role for inhibiting downstream signaling to establish successful infection in the host cells.

Perioperative hypersensitivity (POH) to the neuromuscular blocking drug (NMBD) rocuronium was previously thought to be IgE and mast cell (MC)-mediated. However, the recent seminal observation that rocuronium induces degranulation in murine peritoneal MCs (PMCs) via Mas-related G protein-coupled receptor B2 (MrgprB2) led to the idea that POH to this drug involves the activation of MRGPRX2 (human ortholog of MrgprB2). Furthermore, based on the demonstration that a patient with POH to rocuronium displayed three missense mutations (M196I, L226P and L237P) in MRGPRX2’s transmembrane domains, it was proposed that this hypersensitivity reaction resulted from aberrant activation of this receptor. We found that rocuronium at 20 µg/mL caused degranulation in mouse PMCs via MrgprB2 but required at least 500 µg/mL to induce degranulation in human MCs via MRGPRX2. Furthermore, RBL-2H3 cells transiently expressing M196I, L226P and L237P variants did not display enhanced degranulation in response to rocuronium when compared to the wild-type receptor. These findings provide the first demonstration that rocuronium induces degranulation in human MCs via MRGPRX2. Furthermore, the important differences between MrgprB2 and MRGPRX2 and the inability of rocuronium to induce enhanced response in cells expressing MRGPRX2 variants suggest that the mechanism of its POH is more complex than previously thought.

Sujata Massey catches a rupture from her popular Rei Shimura mystery series and puts pen to paper. The Sleeping Dictionary (published as City of Palaces in India)—a rambling, Victorian era motivated novel; set between 1925 and the end of World War II. The Sleeping Dictionary provides a leaving for the novelist, whose mysteries have pinned to themselves practically every medal in the genre. Sujata Massey, has treaded self-assuredly into the dominion of historical fiction out of her thriller approach to write quite a new thriller while paying attention to history. The Sleeping Dictionary exhales nuovo lease of life into both the bromidic plots of a stray in opposition to the planet, and the forever and a day trendy coming-of-age account by handling curious backdrops and avant-garde confronts.

This paper is divided into two realms. The first portion aims at addressing the post-humanist developments that continually assay to evolve whilst ambivalently opining about the castaways of the world who are the end products of tech-chrysalis. Simultaneously, the second section tries to focus on those very machines that try hard and fast to aid the émigré and refugees. It also attempts to understand the conflicting positions of politics, technology and humanity. Keywords: Post-humanism; Robots; Refugees; Technology; Aid and Rescue.

At finite temperatures, the quantum critical region (QCR) emerges as a consequence of the interplay between thermal and quantum fluctuations. We seek suitable physical quantities, which during dynamics can give prominent response to QCR in the transverse field quantum XY model. We report that the maximum energy absorbed, the nearest neighbor entanglement, and the quantum mutual information of the time-evolved state after a quench of the transverse magnetic field exhibit a faster drop with temperature when the initial magnetic field is taken from within the QCR, compared to the choice of the initial point from different phases. We propose a class of dynamical quantifiers, originating from the response of these physical quantities and show that they can faithfully mimic the equilibrium physics, namely detection of the QCR at finite temperatures.

The survival of intracellular protozoan parasite, Leishmania donovani, the causative agent of Indian visceral leishmaniasis (VL), depends on the activation status of macrophages. l-Arginine, a semi-essential amino acid plays a crucial regulatory role for activation of macrophages. However, the role of l-arginine transport in VL still remains elusive. In this study, we demonstrated that intra-macrophage survival of L. donovani depends on the availability of extracellular l-arginine. Infection of THP-1-derived macrophage/human monocyte-derived macrophage (hMDM) with Leishmania, resulted in upregulation of l-arginine transport. While investigating the involvement of the transporters, we observed that Leishmania survival was greatly impaired when the transporters were blocked either using inhibitor or siRNA-mediated downregulation. CAT-2 was found to be the main isoform associated with l-arginine transport in L. donovani-infected macrophages. l-arginine availability and its transport regulated the host arginase in Leishmania infection. Arginase and inducible nitric oxide synthase (iNOS) expression were reciprocally regulated when assayed using specific inhibitors and siRNA-mediated downregulation. Interestingly, induction of iNOS expression and nitric oxide production were observed in case of inhibition of arginase in infected macrophages. Furthermore, inhibition of l-arginine transport as well as arginase resulted in decreased polyamine production, limiting parasite survival inside macrophages. l-arginine availability and transport regulated Th1/Th2 cytokine levels in case of Leishmania infection. Upregulation of l-arginine transport, induction of host arginase, and enhanced polyamine production were correlated with increased level of IL-10 and decreased level of IL-12 and TNF-α in L. donovani-infected macrophages. Our findings provide clear evidence for targeting the metabolism of l-arginine and l-arginine-metabolizing enzymes as an important therapeutic and prophylactic strategy to treat VL.

Host-defense peptides (HDPs) have an important therapeutic potential against microbial infections but their metabolic instability and cellular cytotoxicity have limited their utility. To overcome these limitations, we utilized five small-molecule, nonpeptide HDP mimetics (smHDPMs) and tested their effects on cytotoxicity, antimicrobial activity, and mast cell (MC) degranulation. None of the smHDPMs displayed cytotoxicity against mouse 3T3 fibroblasts or human transformed liver HepG2 cells. However, one compound had both antifungal and antibacterial activity. Surprisingly, all five compounds induced degranulation in a human MC line, LAD2, and this response was substantially reduced in Mas-related G protein-coupled receptor (GPCR)-X2 (MRGPRX2)-silenced cells. Furthermore, all five compounds induced degranulation in RBL-2H3 cells expressing MRGPRX2 but this response was abolished in cells expressing naturally occurring loss-of-function missense variants G165E (rs141744602) and D184H (rs372988289). Mrgprb2 is the likely mouse ortholog of human MRGPRX2, which is expressed in connective tissue MCs (CTMCs) such as cutaneous and peritoneal MCs (PMCs). All five smHDPMs induced degranulation in wild-type PMCs but not in cells derived from Mrgprb2−/− mice. These findings suggest that smHDPMs could serve as novel targets for the treatment of drug-resistant fungal and bacterial infections because of their ability to harness CTMCs’ host defense functions.

BACKGROUND:Leishmania donovani, belonging to a unicellular protozoan parasite, display the differential level of linkage-specific sialic acids on their surface. Sialic acids binding immunoglobulin-like lectins (siglecs) are a class of membrane-bound receptors present in the haematopoetic cell lineages interact with the linkage-specific sialic acids. Here we aimed to explore the utilization of sialic acids by Leishmania donovani for siglec-mediated binding, phagocytosis, modulation of innate immune response and signaling pathways for establishment of successful infection in the host. METHODOLOGY/PRINCIPLE FINDINGS:We have found enhanced binding of high sialic acids containing virulent strains (AG83+Sias) with siglec-1 and siglec-5 present on macrophages compared to sialidase treated AG83+Sias (AG83-Sias) and low sialic acids-containing avirulent strain (UR6) by flow cytometry. This specific receptor-ligand interaction between sialic acids and siglecs were further confirmed by confocal microscopy. Sialic acids-siglec-1-mediated interaction of AG83+Sias with macrophages induced enhanced phagocytosis. Additionally, sialic acids-siglec-5 interaction demonstrated reduced ROS, NO generation and Th2 dominant cytokine response upon infection with AG83+Sias in contrast to AG83-Sias and UR6. Sialic acids-siglecs binding also facilitated multiplication of intracellular amastigotes. Moreover, AG83+Sias induced sialic acids-siglec-5-mediated upregulation of host phosphatase SHP-1. Such sialic acids-siglec interaction was responsible for further downregulation of MAPKs (p38, ERK and JNK) and PI3K/Akt pathways followed by the reduced translocation of p65 subunit of NF-κβ to the nucleus from cytosol in the downstream signaling pathways. This sequence of events was reversed in AG83-Sias and UR6-infected macrophages. Besides, siglec-knockdown macrophages also showed the reversal of AG83+Sias infection-induced effector functions and downstream signaling events. CONCLUSIONS/SIGNIFICANCES:Taken together, this study demonstrated that virulent parasite (AG83+Sias) establish a unique sialic acids-mediated binding and subsequent phagocytosis in the host cell through the selective exploitation of siglec-1. Additionally, sialic acids-siglec-5 interaction altered the downstream signaling pathways which contributed impairment of immune effector functions of macrophages. To the best of our knowledge, this is a comprehensive report describing sialic acids-siglec interactions and their role in facilitating uptake of the virulent parasite within the host.

The growth and survival of intracellular parasites depends on the availability of extracellular nutrients. Deprivation of nutrients viz glucose or amino acid alters redox balance in mammalian cells as well as some lower organisms. To further understand the relationship, the mechanistic role of L-arginine in regulation of redox mediated survival of Leishmania donovani promastigotes was investigated. L-arginine deprivation from the culture medium was found to inhibit cell growth, reduce proliferation and increase L-arginine uptake. Relative expression of enzymes, involved in L-arginine metabolism, which leads to polyamine and trypanothione biosynthesis, were downregulated causing decreased production of polyamines in L-arginine deprived parasites and cell death. The resultant increase in reactive oxygen species (ROS), due to L-arginine deprivation, correlated with increased NADP+/NADPH ratio, decreased superoxide dismutase (SOD) level, increased lipid peroxidation and reduced thiol content. A deficiency of L-arginine triggered phosphatidyl serine externalization, a change in mitochondrial membrane potential, release of intracellular calcium and cytochrome-c. This finally led to DNA damage in Leishmania promastigotes. In summary, the growth and survival of Leishmania depends on the availability of extracellular L-arginine. In its absence the parasite undergoes ROS mediated, caspase-independent apoptosis-like cell death. Therefore, L-arginine metabolism pathway could be a probable target for controlling the growth of Leishmania parasites and disease pathogenesis.

Objective: To study the in vitro anthelmintic efficacy of Cassia alata (C. alata), Cassia angustifolia (C. angustifolia) and Cassia occidentalis (C. occidentalis). Methods: Crude ethanol extract from leaves of the three plants were prepared in rotary evaporator and different concentrations (10, 20 and 40 mg/mL) of leaf extracts were used for treatment on different representatives of helminthes (Heterakis gallinarum, Raillietina tetragona and Catatropis sp.) from domestic fowl (Gallus gallus domesticus). Loss of motility and death were monitored frequently. Results: C. alata showed early paralysis in all worms treated followed by C. angustifolia. C. occidentalis in combination with C. alata together caused early paralysis in all treated worms than the combination of C. alata with C. angustfolia. While Heterakis gallinarum in control survived for (81.33 ± 2.07) h, treated worms lost their motility at (5.71 ± 0.10) h, (6.60 ± 0.86) h and (13.95 ± 0.43) h with C. angustifolia, C. alata and C. occidentalis respectively at a concentration of 40 mg/mL which showed better efficacy than albendazole. Catatropis sp. survival period was (26.49 ± 1.38) h in control, but with plant treatment, it lost its motility in just (0.57 ± 0.08) h, (1.00 ± 0.12) h and (1.47 ± 0.40) h at 40 mg/mL concentration of C. alata, C. angustifolia and C. occidentalis respectively. Raillietina tetragona on the other hand became paralysed at (1.68 ± 0.27) h, (2.95 ± 0.29) h and (4.13 ± 0.31) h with above concentrations treated with three plants respectively, however in control it survived up to (81.93 ± 4.71) h. Conclusions: This present study indicated broad spectrum vermifugal activity of all plants tested.