Recent advances on pathogenesis,diagnosis,prevention,immunological aspects,and vectors of dengue:A review

Dengue is a vector-borne disease caused by the dengue virus(DENV)of family Flaviviridae.Dengue fever is common in both developed and developing countries.Globally,approximately 400 million cases of dengue fever are reported annually,resulting in approximately 22000 fatalities.Dengue cases in India have progressively increased in the last decade.In recent years,substantial progress has been made in understanding various aspects of dengue,including its pathogenesis,diagnosis,prevention strategies,immunological responses,and the role of vectors in its transmission.The transmission of a positive RNA virus occurs through Aedes mosquitoes,specifically Aedes aegypti and Aedes albopictus.This virus is associated with a wide spectrum of symptoms,ranging from mild undifferentiated fever to severe hemorrhagic fever and shock,posing a potential threat to human health.There are 4 types of antigenically distinct dengue serotypes(DENV-1 to DENV-4)and among them,DENV-2 is more lethal and extremely severe.To overcome the severity of dengue,Dengvaxia is administered to children 9 to 16 years old with evidence of previous dengue infection.The diagnosis of dengue is carried out by ELISA-based non-structural protein(NS1)and immunoglobulin tests.However,there are no specific biomarkers to identify severe disease progression.Climatic factors and temperature play an important role in complex interaction among host,vector,and virus to manifest the severity of dengue.There is a need for the refinement of climate-based disease forecasting models in India to effectively control the spread of dengue.The mosquito repellent should be used periodically to kill or repel the Aedes mosquito to prevent the spread of dengue in humans.

In-silico and in-vitro evaluation of docetaxel and berberine as potential p53 modulating apoptotic inducers in oral squamous cell carcinoma

Objective:To investigate the interaction of p53 with docetaxel and berberine and their anticancer activities against oral squamous cell carcinoma.Methods:The interaction between p53 with docetaxel and berberine was investigated and their mechanisms of action against oral squamous cell carcinoma were studied.Toxicity studies were performed to determine any toxic impact of the drugs on the vital organs of tested animals.Results:In silico results revealed the molecular interaction of docetaxel and berberine with p53 and the molecules were found to be potential p53 inducers.Docetaxel and berberine inhibited the proliferation of cancer cells in a concentration-dependent manner.Flow cytometry analysis revealed that docetaxel and berberine at IC50 concentrations upregulated the expression of p53 in oral squamous cell carcinoma cells,thus triggering apoptotic cell death.In addition,no toxicity was observed in the liver and kidney tissues of mice after docetaxel and berberine treatment.Conclusions:Docetaxel and berberine significantly suppressed the proliferation of oral cancer cells by activating p53 expression and causing apoptotic cell death.Both compounds can be potential agents for the treatment of oral cancer,with little to no toxicity at the tissue level.

Antimalarial activity of a novel series of artemisinin-derived 1, 2, 3-triazole dimers

Objective: To obtain suitable artimisinin-based drug candidates with high antimalarial activity.Methods: Three different reaction schemes were used to synthesize a total of 15 artemisininbased compounds.The first synthetic scheme involved the synthesis of diazido aliphatic and aromatic compounds from commercially available dihalides and azido derivatives of artemisinin.The second scheme consisted of the reaction of dibromoaliphatic compounds with sodium azide in dimethylformamide which yielded the desired compounds.Artemisinin-based compounds on treatment with sodium azide and bromotrimethylsilane in dichloromethane produced the most potent compound GB-2.Another potent compound GB-1 was synthesized from artemisinin by treatment with alcohols in the presence of Aberlyst-15 in anhydrous dichloromethane.The third scheme involved the Huisgen 1,3-dipolar cycloaddition between the synthesized aliphatic and aromatic diazides and two alkyne derivatives of artemisinin to obtain the desired artemisinin dimers with average yields.Results: The best in vitro antiplasmodial activity was shown by the compound GB-2 registering IC_(50) value 0.066 μg/mL against chloroquine-sensitive and 0.865 μg/mL against chloroquineresistant strains of Plasmodium falciparum.It suppressed 59.0% parasitaemia in vivo of rodent malaria parasite Plasmodium berghei in Swiss albino model at 50 μg/kg body weight dosage.Molecular docking interactions of Plasmodium falciparum ATP6(PfATP6) protein revealed strong bonding of GB-2 with Thr255 residue which is likely to be the reason for excellent antimalarial activity of this compound.Conclusion: Two compounds GB-1 and GB-2 exhibited excellent in vitro antiplasmodial activity and fair in vivo antimalarial activity.Of the two, GB-2 showed better activity which could be attributed to its strong bonding interactions with Thr255 as evidenced from the molecular docking study.Study helped in identifying artemisinin analogues possessing good antimalarial properties and further research in structural alterations of the selected molecules should be carried out which may result in obtaining potent drug candidates against the malarial parasite.

Preventive strategies to innovate Japanese encephalitis control in eastern Uttar Pradesh: Accelerating towards zero incidence

Japanese Encephalitis(JE)is a zoonotic mosquito-borne viral disease that primarily affects young children under the age of 15[1].Annually,there are more than 50000 clinical cases and JE causes over 10000 fatalities globally[1].In Japan,South Korea,China and Thailand,where it is now under control or almost entirely eradicated,the disease was initially noted to have a high incidence[1].Later,it expanded to Nepal and India,becoming a serious public health issue in rural regions[1].JE is a flavivirus-based neglected tropical disease that is spread by culicine mosquitoes of the Culex(Cx.)tritaeniorhynchus and Cx.vishnui species[2].

Risk estimation of chronic kidney disease in a leptospirosis endemic area: A case-control study from south Andaman Islands of India

Objective:To estimate the risk of chronic kidney disease in patients with leptospirosis.Methods:All reported(41890)and later confirmed leptospirosis(1990)cases from 2010-2020 were traced by universal sampling.386 Laboratory-confirmed leptospirosis cases were enrolled and 413 age,gender,area,and occupation matched healthy persons were included as controls.Variables including socio-demographic characteristics,medical history,and health-related behaviours were compared between the two groups and association between these variables and reduced estimated glomerular filtration rate(eGFR)was analyzed with multiple linear regression.Results:The median of eGFR was 49.0(27.0,75.0)mL/min/1.73 m^(2) in the cases and 96.0(72.0,121.0)mL/min/1.73 m^(2) in the controls,showing significant differences(P<0.001).Bivariate analysis showed that leptospirosis seropositivitiy,repeat leptospirosis infection,diabetes,male gender,working in field(sun exposure),COVID-19 infection and smoking had statistically significant association with reduced eGFR.Leptospirosis seropositivity had negative effects on eGFR.Multiple linear regression confirmed that leptospirosis seropositivity had negative effects on eGFR(unstandardised β coefficients=−30.86,95%CI−49.7 to−11.9,P<0.001).Conclusions:Chronic kidney disease is a complex disease with multiple risk factors involved.Exposure to leptospirosis is one of the essential factors in accelerating its progression.

Decline of Japanese encephalitis in Eastern Uttar Pradesh,India,2009-2019

Japanese encephalitis(JE),one of the major viral encephalitides,is caused by Flavivirus circulating in rural areas of Asia and Western Pacific regions[1]and is a neglected tropical viral disease due to its endemicity[2].The culicine mosquitoes,mainly of Culex tritaeniorhynchus and Culex vishnui group,are the vectors of JE virus(JEV)[1].Being a neurologic infection,JE manifests with a set of serious symptoms leading to death in many cases and/or change in behaviour of the patients leading to permanent disability[3].

One Health: navigating plague in Madagascar amidst COVID-19

Background Africa sees the surge of plague cases in recent decades,with hotspots in the Democratic Republic of Congo,Madagascar,and Peru.A rodent-borne scourge,the bacterial infection known as plague is transmitted to humans via the sneaky bites of fleas,caused by Yersinia pestis.Bubonic plague has a case fatality rate of 20.8%with treatment,but in places such as Madagascar the mortality rate can increase to 40–70%without treatment.Main text Tragedy strikes in the Ambohidratrimo district as three lives are claimed by the plague outbreak and three more fight for survival in the hospitals,including one man in critical condition,from the Ambohimiadana,Antsaharasty,and Ampanotokana communes,bringing the total plague victims in the area to a grim to five.Presently,the biggest concern is the potential plague spread among humans during the ongoing COVID-19 pandemic.Effective disease control can be achieved through training and empowering local leaders and healthcare providers in rural areas,implementing strategies to reduce human–rodent interactions,promoting water,sanitation and hygiene practices(WASH)practices,and carrying out robust vector,reservoir and pest control,diversified animal surveillance along with human surveillance should be done to more extensively to fill the lacunae of knowledge regarding the animal to human transmission.The lack of diagnostic laboratories equipped represents a major hurdle in the early detection of plague in rural areas.To effectively combat plague,these tests must be made more widely available.Additionally,raising awareness among the general population through various means such as campaigns,posters and social media about the signs,symptoms,prevention,and infection control during funerals would greatly decrease the number of cases.Furthermore,healthcare professionals should be trained on the latest methods of identifying cases,controlling infections and protecting themselves from the disease.Conclusions Despite being endemic to Madagascar,the outbreak’s pace is unparalleled,and it may spread to non-endemic areas.The utilization of a One Health strategy that encompasses various disciplines is crucial for minimizing catastrophe risk,antibiotic resistance,and outbreak readiness.Collaboration across sectors and proper planning ensures efficient and consistent communication,risk management,and credibility during disease outbreaks.