Multidrug resistance (MDR) in cancer caused due to overexpression of ABC drug transporters is a major problem in modern chemotherapy. Molecular investigations on MDR have revealed that the resistance is due to various transport proteins of the ABC superfamily which include Phosphoglycoprotein (P-gp/MDR1/ ABCB1), multidrug resistance-associated protein-1 (MRP1), and the breast cancer resistance protein (BCRP). They have been characterized functionally and are considered as major players in the development of MDR in cancer cells. These ATP-dependent transporter proteins cause MDR either by decreased uptake of the drug or increased efflux of the drug from the target organelles. Several MDR-reversing agents are being developed and are in various stages of clinical trials. The first three generations of ABC modulators such as quinine, verapamil, cyclosporine-A, tariquitor, PSC 833, LY335979, and GF120918 required to be administered in high doses to reverse MDR and were associated with adverse effects. Additionally, these modulators non-selectively inhibit ABC and adversely accumulate chemotherapeutic drugs in brain and kidney. Currently, research has stepped up towards reversing MDR by using natural products which exhibitted potential as chemosensitizers. Globally, there is a rich biodiversity of natural products which can be sourced for developing drugs. These products may provide more lead compounds with superior activity, foremost to the development of more effective therapies for MDR cancer cells. Here, we briefly review the status of natural products for reversing MDR modulators, and discuss the long term goal of MDR strategies in current clinical settings.

Zoonotic diseases affect resource-poor tropical communities disproportionately, and are linked to human use and modification of ecosystems. Disentangling the socio-ecological mechanisms by which ecosystem change precipitates impacts of pathogens is critical for predicting disease risk and designing effective intervention strategies. Despite the global "One Health" initiative, predictive models for tropical zoonotic diseases often focus on narrow ranges of risk factors and are rarely scaled to intervention programs and ecosystem use. This study uses a participatory, co-production approach to address this disconnect between science, policy and implementation, by developing more informative disease models for a fatal tick-borne viral haemorrhagic disease, Kyasanur Forest Disease (KFD), that is spreading across degraded forest ecosystems in India. We integrated knowledge across disciplines to identify key risk factors and needs with actors and beneficiaries across the relevant policy sectors, to understand disease patterns and develop decision support tools. Human case locations (2014-2018) and spatial machine learning quantified the relative role of risk factors, including forest cover and loss, host densities and public health access, in driving landscape-scale disease patterns in a long-affected district (Shivamogga, Karnataka State). Models combining forest metrics, livestock densities and elevation accurately predicted spatial patterns in human KFD cases (2014-2018). Consistent with suggestions that KFD is an "ecotonal" disease, landscapes at higher risk for human KFD contained diverse forest-plantation mosaics with high coverage of moist evergreen forest and plantation, high PLOS NEGLECTED TROPICAL DISEASES

We propose that the oxidative stress response induced by the dengue virus may trigger the inflammatory cytokine responses in dengue severity and thereby contributes to the pathogenesis of the disease; however the interplay between the oxidative response and inflammatory activity in disease virulence needs further study.

There are about five more common, including Wuchereria bancrofti and Brugia malayi, and four less common filarial parasites infecting human. Genetic analysis of W. bancrofti populations in India showed that two strains of the species are prevalent in the country. The adult filarial parasites are tissue specific in the human host and their embryonic stage, called microfilariae (mf), are found in the blood or skin of the host, depending upon the species of the parasite. Three genetically determined physiological races exist in W. bancrofti and B. malayi, based on the microfilarial periodicity. They are the nocturnally periodic, nocturnally subperiodic and diurnally subperiodic forms. The susceptibility of a mosquito species to filarial infection depends on various factors, which could be genetic, physiological or physical. Survival analysis of Culex quinquefasciatus infected with W. bancrofti showed that the parasite load in the mosquito is a risk factor of vector survival. The extrinsic life cycle of the parasite is initiated when the mf are ingested by a mosquito vector during feeding on the host blood. On maturity, most of the infective L3 stage larvae migrate to the head and proboscis of the mosquito to get transmitted to the mammalian host during subsequent feeding. They develop to the adult L5 stage and the period of development and the longevity of the parasites varies according to the species of the nematode and the mammalian host. The rate of production of mf by the adult female was found to be stable at least for a period of five years. The life span of the mf has some influence on the dynamics of transmission of filariasis. Recent studies show that the endosymbiont, Wolbachia, plays an important role in the survival of filarial parasites. The possibility of in vitro and in vivo culture of filarial parasites is also reviewed.

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Oxidative stress in viral infections has been suggested. The study was carried out to assess the oxidative stress in the different clinical spectrums of dengue infection and to evaluate if thrombocytopenia is associated with lipid and protein oxidative injury. Twenty-seven dengue fever (DF), 32 dengue hemorrhagic fever (DHF) and 21 dengue shock syndrome (DSS) cases were studied at 3, 5 and 7 days of illness. Sixty-three healthy subjects were selected as controls. Serum protein carbonyls (PCOs), malendialdehyde (MDA) and total antioxidant status (TAS) were estimated in blood. Dengue infected individuals had significantly high levels of PCOs and MDA on the three days tested in comparison to controls. In DF cases, no significant changes in the levels of MDA and PCOs were found in course of time. However, among DHF and DSS, significant increase in MDA levels was found in the fifth and seventh day samples in comparison to their respective third day sample (P < 0.05). Using one way ANOVA, high PCOs levels were found in DSS in comparison to DF and DHF cases on all the three days tested (P < 0.001). TAS levels were found to be low among DSS on days 5 and 7 and day 7 in DHF when compared with DF cases. Correlation analysis between MDA and hematocrit revealed a significant positive association between them in DHF and DSS on day 5 (DHF r = 0.372; p = 0.024 and DSS r = 0.535; p = 0.0-01) and day 7 (DHF r = 0.412; p = 0.003 and DSS r = 0.765; p < 0.0001). There was an important negative correlation between platelet count and plasma lipid peroxidation levels among DHF and DSS on all three days tested [day 3 (DHF r = -0.392; p = 0.012 and DSS r = -0.453; p = 0.004), day 5 (DHF r = -0.592; p < 0.001 and DSS r = -0.581; p < 0.001) and day 7 (DHF r = -0.418; p = 0.001 and DSS r = -0.515; p = 0.002)]. This study concludes that an increase in oxidative stress was found in dengue viral infection. The level of oxidative stress was maximal in DSS followed by DHF and its severity was minimal in DF. The thrombocytopenia of dengue infection was associated with the extent of lipid peroxidation. Future studies might be carried out to find the role of oxidative damage in the ethiopathogenesis of thrombocytopenia and vascular leakage in dengue infection.

Mosquito-borne diseases represent a deadly threat for millions of people worldwide. Eco-friendly mosquitocides are a priority. In Ayurvedic medicine, Plectranthus species have been used to treat heart disease, convulsions, spasmodic pain and painful urination. In this research, we evaluated the acute toxicity of essential oil from Plectranthus barbatus and its major constituents, against larvae of the malaria vector Anopheles subpictus, the dengue vector Aedes albopictus and the Japanese encephalitis vector Culex tritaeniorhynchus. The chemical composition of P. barbatus essential oil was analyzed by gas chromatography-mass spectroscopy. Nineteen components were identified. Major constituents were eugenol (31.12%), α-pinene (19.38%) and β-caryophyllene (18.42%). Acute toxicity against early third-instar larvae of An. subpictus, Ae. albopictus and Cx. tritaeniorhynchus was investigated. The essential oil had a significant toxic effect against larvae of An. subpictus, Ae. albopictus and Cx. tritaeniorhynchus, with 50% lethal concentration (LC50) values of 84.20, 87.25 and 94.34 μg/ml and 90% lethal concentration (LC90) values of 165.25, 170.56 and 179.58 μg/ml, respectively. Concerning major constituents, eugenol, α-pinene and β-caryophyllene appeared to be most effective against An. subpictus (LC50 = 25.45, 32.09 and 41.66 μg/ml, respectively), followed by Ae. albopictus (LC50 = 28.14, 34.09 and 44.77 μg/ml, respectively) and Cx. tritaeniorhynchus (LC50 = 30.80, 36.75 and 48.17 μg/ml, respectively). Overall, the chance to use metabolites from P. barbatus essential oil against mosquito vectors seems promising, since they are effective at low doses and could be an advantageous alternative to build newer and safer mosquito control tools.