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Invasion of the malaria vector Anopheles stephensi across the Horn of Africa threatens control efforts across the continent, particularly in urban settings where the vector is able to proliferate. Malaria transmission is primarily determined by the abundance of dominant vectors, which often varies seasonally with rainfall. However, it remains unclear how An. stephensi abundance changes throughout the year, despite this being a crucial input to surveillance and control activities. We collate longitudinal catch data from across its endemic range to better understand the vector's seasonal dynamics and explore the implications of this seasonality for malaria surveillance and control across the Horn of Africa. Our analyses reveal pronounced variation in seasonal dynamics, the timing and nature of which are poorly predicted by rainfall patterns. Instead, they are associated with temperature and patterns of land use; frequently differing between rural and urban settings. Our results show that timing entomological surveys to coincide with rainy periods is unlikely to improve the likelihood of detecting An. stephensi. Integrating these results into a malaria transmission model, we show that timing indoor residual spraying campaigns to coincide with peak rainfall offers little improvement in reducing disease burden compared to starting in a random month. Our results suggest that unlike other malaria vectors in Africa, rainfall may be a poor guide to predicting the timing of peaks in An. stephensi-driven malaria transmission. This highlights the urgent need for longitudinal entomological monitoring of the vector in its new environments given recent invasion and potential spread across the continent.
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Anopheles , Malaria , Animales , Humanos , Malaria/epidemiología , Malaria/prevención & control , Estaciones del Año , Mosquitos Vectores , África/epidemiología , Control de MosquitosRESUMEN
Interferons control viral infection by inducing the expression of antiviral effector proteins encoded by interferon-stimulated genes (ISGs). The field has mostly focused on identifying individual antiviral ISG effectors and defining their mechanisms of action. However, fundamental gaps in knowledge about the interferon response remain. For example, it is not known how many ISGs are required to protect cells from a particular virus, though it is theorized that numerous ISGs act in concert to achieve viral inhibition. Here, we used CRISPR-based loss-of-function screens to identify a markedly limited set of ISGs that confer interferon-mediated suppression of a model alphavirus, Venezuelan equine encephalitis virus (VEEV). We show via combinatorial gene targeting that three antiviral effectors-ZAP, IFIT3, and IFIT1-together constitute the majority of interferon-mediated restriction of VEEV, while accounting for < 0.5% of the interferon-induced transcriptome. Together, our data suggest a refined model of the antiviral interferon response in which a small subset of "dominant" ISGs may confer the bulk of the inhibition of a given virus.
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Virus de la Encefalitis Equina Venezolana , Virus , Animales , Caballos , Interferones , Línea Celular , Replicación Viral , Antivirales/farmacología , Virus de la Encefalitis Equina Venezolana/fisiologíaRESUMEN
Hazardous cyanide anions (CN-) are increasingly threatening the environment and human health due to their widespread use in industry and many other fields. Over the past three decades, a large number of probes have been reported to sensitively and selectively detect this toxic anion, while a rather limited number of ratiometric fluorescent probes have been developed. The ratiometric probes have significant potential in bio-imaging and biomedical applications because of the ability to detect CN- in a quick, convenient and affordable way. In this review, we introduce 42 ratiometric fluorescent probes reported in the past 6 years (2018-2023) for CN- detection. Our description includes the chemical structures, photo-physical properties, CN- sensing mechanisms, solution color changes, limits of detection (LODs) and/or various applications of these chemical probes. This review provides guidelines for design and development of a new ratiometric probe for effective CN- detection.
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Cianuros , Colorantes Fluorescentes , Humanos , Colorantes Fluorescentes/química , Cianuros/química , Espectrometría de Fluorescencia , Límite de DetecciónRESUMEN
This work used a highly flexible, sustainable polyimide tape as a substrate to deposit ductile-natured carbonaceous Ni3N (C/Ni3N@polyimide) material for supercapacitor application. C/Ni3N was prepared using a co-sputtering technique, and this method also provided better adhesion of the electrode material over the substrate, which is helpful in improving bending performance. The ductile behavior of the sputter-grown electrode and the high flexibility of the polyimide tape provide ultimate flexibility to the C/Ni3N@polyimide-based supercapacitor. To achieve optimum electrochemical performance, a series of electrochemical tests were done in the presence of various electrolytes. Further, a flexible asymmetric supercapacitor (NC-FSC) (C/Ni3N//carbon@polyimide) was assembled by using C/Ni3N as a cathode and a carbon thin film as an anode, separated by a GF/C-glass microfiber soaked in optimized 1 M Li2SO4 aqueous electrolyte. The NC-FSC offers a capacitance of 324 mF cm-2 with a high areal energy density of 115.26 µWh cm-2 and a power density of 811 µW cm-2, with ideal bending performance.
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OBJECTIVE: This study aimed to assess 30-day morbidity and mortality rates following cholecystectomy for benign gallbladder disease and identify the factors associated with complications. SUMMARY BACKGROUND DATA: Although cholecystectomy is common for benign gallbladder disease, there is a gap in the knowledge of the current practice and variations on a global level. METHODS: A prospective, international, observational collaborative cohort study of consecutive patients undergoing cholecystectomy for benign gallbladder disease from participating hospitals in 57 countries between January 1 and June 30, 2022, was performed. Univariate and multivariate logistic regression models were used to identify preoperative and operative variables associated with 30-day postoperative outcomes. RESULTS: Data of 21,706 surgical patients from 57 countries were included in the analysis. A total of 10,821 (49.9%), 4,263 (19.7%), and 6,622 (30.5%) cholecystectomies were performed in the elective, emergency, and delayed settings, respectively. Thirty-day postoperative complications were observed in 1,738 patients (8.0%), including mortality in 83 patients (0.4%). Bile leaks (Strasberg grade A) were reported in 278 (1.3%) patients and severe bile duct injuries (Strasberg grades B-E) were reported in 48 (0.2%) patients. Patient age, ASA physical status class, surgical setting, operative approach and Nassar operative difficulty grade were identified as the five predictors demonstrating the highest relative importance in predicting postoperative complications. CONCLUSION: This multinational observational collaborative cohort study presents a comprehensive report of the current practices and outcomes of cholecystectomy for benign gallbladder disease. Ongoing global collaborative evaluations and initiatives are needed to promote quality assurance and improvement in cholecystectomy.
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Probiotic microorganisms have been used for therapeutic purposes for over a century, and recent advances in biotechnology and genetic engineering have opened up new possibilities for developing therapeutic approaches using indigenous probiotic microorganisms. Diseases are often related to metabolic and immunological factors, which play a critical role in their onset. With the help of advanced genetic tools, probiotics can be modified to produce or secrete important therapeutic peptides directly into mucosal sites, increasing their effectiveness. One potential approach to enhancing human health is through the use of designer probiotics, which possess immunogenic characteristics. These genetically engineered probiotics hold promise in providing novel therapeutic options. In addition to their immunogenic properties, designer probiotics can also be equipped with sensors and genetic circuits, enabling them to detect a range of diseases with remarkable precision. Such capabilities may significantly advance disease diagnosis and management. Furthermore, designer probiotics have the potential to be used in diagnostic applications, offering a less invasive and more cost-effective alternative to conventional diagnostic techniques. This review offers an overview of the different functional aspects of the designer probiotics and their effectiveness on different diseases and also, we have emphasized their limitations and future implications. A comprehensive understanding of these functional attributes may pave the way for new avenues of prevention and the development of effective therapies for a range of diseases.
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Probióticos , Humanos , Probióticos/uso terapéutico , Probióticos/metabolismo , Ingeniería Genética , Biotecnología , Redes Reguladoras de GenesRESUMEN
An eco-friendly facile synthesis of a series of twenty 1-(4/6-substitutedbenzo[d]thiazol-2-yl)-3-(phenyl/substitutedphenyl)indeno[1,2-c]pyrazol-4(1H)-ones 7a-t was achieved by the reaction of 2-(benzoyl/substitutedbenzoyl)-(1H)-indene-1,3(2H)-dione 3a-t and 2-hydrazinyl-4/6-substitutedbenzo[d]thiazole 6a-t in presence of freshly dried ethanol and glacial acetic acid under reflux conditions in good yields. The newly synthesized derivatives were well characterized using different physical and spectral techniques (FTIR, 1H NMR & 13C NMR, and HRMS). All the compounds were subjected to assess their in vitro α-amylase and glucose diffusion inhibitory activity. Amongst them, the compounds 7i and 7l showed better α-amylase inhibitory activity demonstrating IC50 values of 92.99±1.94 µg/mL and 95.41±3.92 µg/mL, respectively in comparison to the standard drug acarbose (IC50 value of 103.60±2.15 µg/mL). The derivatives 7d and 7k exhibited good glucose diffusion inhibition with values of 2.25±1.16 µg/mL and 2.63±1.45 µg/mL, respectively with standard reference acarbose (2.76±0.55 µg/mL). The observed α-amylase inhibitory activity findings were corroborated through molecular docking investigations, particularly for the highly active compounds 7i (binding energy -8.0 kcal/mol) and 7l (binding energy -8.2 kcal/mol) respectively, in comparison to acarbose with a value of binding energy -6.9 kcal/mol for α-amylase.
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Acarbosa , Glucosa , Relación Estructura-Actividad , Estructura Molecular , Simulación del Acoplamiento Molecular , alfa-Amilasas/metabolismo , Benzotiazoles/farmacología , alfa-Glucosidasas/metabolismo , Inhibidores de Glicósido Hidrolasas/farmacologíaRESUMEN
In this study, a simple Schiff base sensor 1-(((4-nitrophenyl)imino)methyl)naphthalen-2-ol(NNM) has been used for chemosensing of metal ions. The metal sensing properties of sensor NNM have been investigated using UV-visible and fluorescence spectroscopic approaches. The spectral investigations revealed a red shift in absorption spectra and quenching in the emission band of the ligand molecule in the presence of Cu2+ and Ni2+ ions. The binding stoichiometry of sensor NNM for the analyte (Cu2+ and Ni2+ ions) has been investigated by the Job's plot analysis and found to be 1:1 (NNM:Analyte). The data of the Benesi-Hildebrand plot demonstrated that NNM detected Cu2+ and Ni2+ ions in nanomolar quantity. The binding insights among NNM and analytes (Cu2+ and Ni2+ ions) have been confirmed by shifted IR signals. Moreover, the reusabilty of the sensor has been investigated using an EDTA solution. In addition, the sensor NNM also successfully applied to real water samples for the identification and measurement of Cu2+ and Ni2+ ions. Hence, this system could be highly applicable in environmental and biological applications.
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BACKGROUND: Transmission Assessment Survey (TAS) is the WHO recommended method used for decision-making to stop or continue the MDA in lymphatic filariasis (LF) elimination programme. The WHO has also recommended Molecular Xenomonitoring (MX) of LF infection in vectors as an adjunct tool in settings under post-MDA or validation period. Screening of non-vectors by MX in post-MDA / validation settings could be useful to prevent a resurgence of LF infection, as there might be low abundance of vectors, especially in some seasons. In this study, we investigated the presence of LF infection in non-vectors in an area endemic for LF and has undergone many rounds of annual MDA with two drugs (Diethylcarbamazine and Albendazole, DA) and two rounds of triple drug regimens (Ivermectin + DA). METHODS AND RESULTS: Mosquitoes were collected from selected villages of Yadgir district in Karnataka state, India, during 2019. A total of 680 female mosquitoes were collected, identified morphologically by species and separated as pools. The female mosquitoes belonging to 3 species viz., Anopheles subpictus, Culex gelidus and Culex quinquefaciatus were separated, pooled, and the DNA extracted using less expensive method and followed by LDR based real-time PCR assay for detecting Wuchereria bancrofti infection in vector as well as non-vector mosquitoes. One pool out of 6 pools of An. subpictus, 2 pools out of 6 pools of Cx. gelidus, and 4 pools out of 8 pools of Cx. quinquefaciatus were found to be positive for W. bancrofti infection by RT-PCR. The infection rate in vectors and non-vectors was found to be 1.8% (95% CI: 0.5-4.2%) and 0.9% (95% CI: 0.2-2.3%), respectively. CONCLUSIONS: Our study showed that non-vectors also harbour W. bancrofti, thus opening an opportunity of using these mosquitoes as surrogate vectors for assessing risk of transmission to humans in LF endemic and post MDA areas.
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Anopheles , Filariasis Linfática , Femenino , Humanos , Animales , Filariasis Linfática/epidemiología , Filariasis Linfática/prevención & control , Wuchereria bancrofti/genética , India , Mosquitos Vectores , Anopheles/genética , ADNRESUMEN
Most of the Escherichia coli turned into serious pathogens or developed antibiotic resistance, mainly due to their ability to show different phenotypic traits. In order to overcome the resistance to these antibiotics, the use of essential oils (EOs) is of great significance against highly pathogenic microorganisms. This study has been made to compare the in vitro antibacterial activity and further validated the same through the molecular docking study of 13 antibiotics such as ciprofloxacin, chloramphenicol, erythromycin, ampicillin, cefotaxime, rifampicin, kanamycin, vancomycin, streptomycin, penicillin, nalidixic acid, trimethoprim, and polymyxin, and 10 EOs such as garlic, tulsi, neem, clove, thyme, peppermint, coriander, tea, lavender, and eucalyptus against the target protein (DNA gyrase) of E. coli MTCC443. E. coli Microbial Type Culture Collection 443 was found to be highly sensitive to ciprofloxacin (zone of inhibition [ZOI], 2.5 cm ±0.1) and chloramphenicol (ZOI, 1.8 cm ±0.1), whereas garlic oil (ZOI, 5.5 cm ±0.1) and coriander oil (ZOI, 4.4 cm ±0.1) were found comparatively most effective. Further, the in silico investigation observed the same; ciprofloxacin (binding affinity: -7.2 kcal/mol) and chloramphenicol (binding affinity: -6.6 kcal/mol). Penicillin (binding affinity: -4.2 kcal/mol) and polymyxin (binding affinity: -0.3 kcal/mol) were found to be least effective against the tested microbe, whereas vancomycin (binding affinity: +0.8 kcal/mol) had no effect on it. Garlic (binding affinity: -7.8 kcal/mol), coriander (binding affinity: -6.8 kcal/mol), peppermint (binding affinity: -6.2 kcal/mol), and neem (binding affinity: -6.2 kcal/mol) oil exhibited the potent antibacterial activity against E. coli MTCC443, whereas thyme (binding affinity: -6.1 kcal/mol), tea tree (binding affinity: -4.9 kcal/mol), and tulsi (binding affinity: -3.8 kcal/mol) oil were observed moderately effective. Eucalyptus (binding affinity: -2.9 kcal/mol) and lavender (binding affinity: -2.8 kcal/mol) oil were found to be the least effective among all the oils tested. The pharmacokinetics and networking were performed to the pharmacology of the potential compounds.
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Antibacterianos , Escherichia coli , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Aceites Volátiles , Antibacterianos/farmacología , Antibacterianos/química , Aceites Volátiles/farmacología , Aceites Volátiles/química , Escherichia coli/efectos de los fármacos , Aceites de Plantas/química , Aceites de Plantas/farmacología , Girasa de ADN/metabolismo , Girasa de ADN/químicaRESUMEN
Lung cancer holds the position of being the primary cause of cancer-related fatalities on a global scale. Furthermore, it exhibits the highest mortality rate among all types of cancer. The survival rate within a span of 5 years is less than 20%, primarily due to the fact that the disease is often diagnosed at an advanced stage, resulting in less effective treatment options compared to earlier stages. There are two main types of primary lung cancer: nonsmall-cell lung cancer, which accounts for approximately 80%-85% of all cases, and small-cell lung cancer, which is categorized based on the specific type of cells in which the cancer originates. The understanding of the biology of this disease and the identification of oncogenic driver alterations have significantly transformed the landscape of therapeutic approaches. Long noncoding RNAs (lncRNAs) play a crucial role in regulating various physiological and pathological processes through diverse molecular mechanisms. Among these lncRNAs, lncRNA H19, initially identified as an oncofetal transcript, has garnered significant attention due to its elevated expression in numerous tumors. Extensive research has confirmed its involvement in tumorigenesis and malignant progression by promoting cell growth, invasion, migration, epithelial-mesenchymal transition, metastasis, and therapy resistance. This comprehensive review aims to provide an overview of the aberrant overexpression of lncRNA H19 and the molecular pathways through which it contributes to the advancement of lung cancer. The findings of this review highlight the potential for further investigation into the diagnosis and treatment of this disease, offering promising avenues for future research.
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Neoplasias Pulmonares , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/diagnóstico , Transición Epitelial-Mesenquimal , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Regulación Neoplásica de la Expresión GénicaRESUMEN
Outbreaks of acute encephalitis syndrome (AES) with unknown aetiology are reported every year in Gorakhpur district, Uttar Pradesh, India, and Orientia tsutsugamushi, the rickettsial pathogen, responsible for scrub typhus has been attributed as the primary cause of AES problem. However, information on the prevalence of other rickettsial infections is lacking. Hence, this study was carried out to assess any occurrence of tick- and flea-borne rickettsial agents in villages reporting AES cases in this district. In total, 825 peridomestic small mammals were trapped, by setting 9254 Sherman traps in four villages with a trap success rate of 8.9%. The Asian house shrew, Suncus murinus, constituted the predominant animal species (56.2%) and contributed to the maximum number (87.37%) of ectoparasites. In total, 1552 ectoparasites comprising two species of ticks and one species each of flea and louse were retrieved from the trapped rodents/shrews. Rhipicephalus sanguineus, the brown dog tick, was the predominant species retrieved from the trapped rodents/shrews, and the overall infestation rate was 1.75 per animal. In total, 4428 ectoparasites comprising five tick species, three louse species and one flea species were collected from 1798 domestic animals screened. Rhipicephalus microplus was the predominant tick species collected from the domestic animals. The cat flea, Ctenocephalides felis, constituted 1.5% of the total ectoparasites. Of all the ectoparasite samples (5980) from domestic animals and rodents, tested as 1211 pools through real-time PCR assays, 64 pools were positive for 23S rRNA gene of rickettsial agents. The PCR-positive samples were subjected to multi-locus sequence typing (MLST). In BLAST and phylogenetic analysis, the ectoparasites were found to harbour Rickettsia asembonensis (n = 9), Rickettsia conorii (n = 3), Rickettsia massiliae (n = 29) and Candidatus Rickettsia senegalensis (n = 1). A total of 22 pools were detected to have multiple rickettsial agents. The prevalence of fleas and high abundance of tick vectors with natural infections of rickettsial agents indicates the risk of transmission of tick- and flea-borne rickettsial diseases in rural villages of Gorakhpur. Further epidemiological studies are required to confirm the transmission of these agents to humans.
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Encefalopatía Aguda Febril , Enfermedades de los Gatos , Ctenocephalides , Enfermedades de los Perros , Rhipicephalus sanguineus , Infecciones por Rickettsia , Rickettsia , Siphonaptera , Perros , Gatos , Animales , Humanos , Siphonaptera/microbiología , Tipificación de Secuencias Multilocus/veterinaria , Musarañas/genética , Musarañas/microbiología , Encefalopatía Aguda Febril/veterinaria , Filogenia , Prevalencia , Rhipicephalus sanguineus/genética , Rickettsia/genética , Infecciones por Rickettsia/epidemiología , Infecciones por Rickettsia/veterinaria , Infecciones por Rickettsia/microbiología , Ctenocephalides/microbiologíaRESUMEN
BACKGROUND OBJECTIVES: Scrub typhus, caused by Orientia tsutsugamushi present in small mammals harbouring the ectoparasites. A study was undertaken to detect the pathogen present in small mammals and its ectoparasites in the scrub typhus-reported areas. METHODS: The small mammals (rodents/shrews) and its ectoparasites were screened for O. tsutsugamushi using nested PCR amplification of the groEL gene. Small mammals were collected by trapping and screened for ectoparasites (mites, ticks and fleas) by combing method. RESULTS: All the chigger mites collected were tested negative for O. tsutsugamushi . Interestingly, adult non-trombiculid mites ( Oribatida sp., Dermanyssus gallinae ), fleas ( Xenopsylla astia, X. cheopis, Ctenophalides felis and Ctenophalides sp.) and ticks ( Rhipicephalus sanguineus , R. haemaphysaloides ) screened were found to be positive for O. tsutsugamushi , which the authors believe is the first report on these species globally. Bandicota bengalensis with O. tsutsugamushi infection is reported for the first time in India. The O. tsutsugamushi groEL sequences from the positive samples were similar to the reference strains, Karp and Ikeda and phylogenetically clustered in clade IV with less evolutionary divergence. The blood samples of Rattus rattus , Suncus murinus and B. bengalensis collected from this area were tested positive for O. tsutsugamushi ; interestingly, the sequence similarity was much pronounced with their ectoparasites indicating the transmission of the pathogen to host or vice versa . INTERPRETATION CONCLUSIONS: The outcome of the present investigations widened our scope on the pathogens present in ectoparasites and rodents/shrews from this area. This will help to formulate the required vector control methods to combat zoonotic diseases.
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Orientia tsutsugamushi , Tifus por Ácaros , Garrapatas , Trombiculidae , Ratas , Animales , Tifus por Ácaros/epidemiología , Orientia tsutsugamushi/genética , Musarañas , India/epidemiología , Roedores/parasitología , Trombiculidae/genéticaRESUMEN
Poly(ADP-ribose) polymerase-1 (PARP-1) is a DNA damage sensor and contributes to both DNA repair and cell death processes. However, how PARP-1 signaling is regulated to switch its function from DNA repair to cell death remains largely unknown. Here, we found that PARP-1 plays a central role in alkylating agent-induced PARthanatic cancer cell death. Lysine demethylase 6B (KDM6B) was identified as a key regulator of PARthanatos. Loss of KDM6B protein or its demethylase activity conferred cancer cell resistance to PARthanatic cell death in response to alkylating agents. Mechanistically, KDM6B knockout suppressed methylation at the promoter of O6-methylguanine-DNA methyltransferase (MGMT) to enhance MGMT expression and its direct DNA repair function, thereby inhibiting DNA damage-evoked PARP-1 hyperactivation and subsequent cell death. Moreover, KDM6B knockout triggered sustained Chk1 phosphorylation and activated a second XRCC1-dependent repair machinery to fix DNA damage evading from MGMT repair. Inhibition of MGMT or checkpoint response re-sensitized KDM6B deficient cells to PARthanatos induced by alkylating agents. These findings provide new molecular insights into epigenetic regulation of PARP-1 signaling mediating DNA repair or cell death and identify KDM6B as a biomarker for prediction of cancer cell vulnerability to alkylating agent treatment.
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Dacarbazina , Parthanatos , Alquilantes , ADN , Reparación del ADN , Dacarbazina/farmacología , Epigénesis Genética , Guanina/análogos & derivados , O(6)-Metilguanina-ADN Metiltransferasa/genética , O(6)-Metilguanina-ADN Metiltransferasa/metabolismo , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Temozolomida/farmacologíaRESUMEN
The AP1 transcription factor ΔFOSB, a splice variant of FOSB, accumulates in the brain in response to chronic insults such as exposure to drugs of abuse, depression, Alzheimer's disease and tardive dyskinesias, and mediates subsequent long-term neuroadaptations. ΔFOSB forms heterodimers with other AP1 transcription factors, e.g. JUND, that bind DNA under control of a putative cysteine-based redox switch. Here, we reveal the structural basis of the redox switch by determining a key missing crystal structure in a trio, the ΔFOSB/JUND bZIP domains in the reduced, DNA-free form. Screening a cysteine-focused library containing 3200 thiol-reactive compounds, we identify specific compounds that target the redox switch, validate their activity biochemically and in cell-based assays, and show that they are well tolerated in different cell lines despite their general potential to bind to cysteines covalently. A crystal structure of the ΔFOSB/JUND bZIP domains in complex with a redox-switch-targeting compound reveals a deep compound-binding pocket near the DNA-binding site. We demonstrate that ΔFOSB, and potentially other, related AP1 transcription factors, can be targeted specifically and discriminately by exploiting unique structural features such as the redox switch and the binding partner to modulate biological function despite these proteins previously being thought to be undruggable.
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Cisteína , Proteínas Proto-Oncogénicas c-fos , Proteínas Proto-Oncogénicas c-fos/metabolismo , Cisteína/genética , Cisteína/metabolismo , Regulación de la Expresión Génica , ADN/genética , ADN/metabolismo , Oxidación-Reducción , Factor de Transcripción AP-1/genética , Factor de Transcripción AP-1/metabolismoRESUMEN
Cutaneous leishmaniasis (CL) is often considered a 'great imitator' and is the most common form of leishmaniasis. The Leishmania species responsible for CL varies among countries, as these species exhibit specific distribution patterns. The increased mobility of people across countries has resulted in the imported incidences of leishmaniasis caused by non-endemic species of Leishmania. During 2023, we confirmed three CL cases caused by L. major from Kerala, India, and upon detailed investigation, these were identified to be imported from the Middle East and Kazakhstan regions. This is the first report of CL caused by L. major from Kerala. The lesion morphology, detection of anti-rK 39 antibody and Leishmania parasite DNA from the blood samples were the unique observations of these cases. Kerala, being an emerging endemic zone of visceral leishmaniasis (VL) and CL, the imported incidences of leishmaniasis by non-endemic species can pose a significant threat, potentially initiating new transmission cycles of leishmaniasis caused by non-endemic species.
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Leishmania major , Leishmaniasis Cutánea , India/epidemiología , Leishmaniasis Cutánea/parasitología , Leishmaniasis Cutánea/epidemiología , Leishmaniasis Cutánea/diagnóstico , Humanos , Masculino , Leishmania major/aislamiento & purificación , Leishmania major/genética , Adulto , Femenino , Enfermedades Transmisibles Importadas/parasitología , Enfermedades Transmisibles Importadas/epidemiología , Persona de Mediana Edad , ADN Protozoario/genética , Anticuerpos Antiprotozoarios/sangreRESUMEN
Malaria has a historical presence in the Dakshina Kannada (D.K.) and Udupi districts of Karnataka, India. To understand the potential involvement of anopheline fauna in malaria transmission, we conducted an exploratory entomological survey. The study is crucial given the decreasing malaria incidence in these districts in recent years. From September 2022 to August 2023, we collected indoor resting mosquitoes using a manual aspirator at 27 randomly chosen sites within three distinct resting habitats (human dwellings, cattle sheds, and construction sites) in the urban areas of Udupi and Dakshina Kannada districts. Mosquitoes were morphologically identified, and anopheline specimens were tested for the presence of malarial parasite by polymerase chain reaction (PCR) analysis. We collected a total of 1810 mosquitoes, comprising 21 species distributed across five genera. Culex emerged as the predominant genus, constituting 84.4% of the collected specimens, while Anopheles accounted for 5.4%. Among the observed species, Culex quinquefasciatus was predominant, comprising 77.9% of the mosquito specimens collected in this study. Two malaria vectors, An. stephensi and An. subpictus complex, constituted 16.3% and 1.0% of the total anophelines collected, respectively. None of the 96 female anophelines was tested positive for Plasmodium infection. Our findings suggest that Anopheles mosquitoes prefer resting in cattle sheds over human dwellings. While our study identified two malaria vectors, they were present at low densities. To gain a more comprehensive understanding of the dynamics of these vector mosquitoes, it is essential to conduct long-term surveillance to monitor their prevalence and role in malaria transmission.
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Anopheles , Ecosistema , Malaria , Mosquitos Vectores , Animales , India/epidemiología , Anopheles/parasitología , Anopheles/fisiología , Anopheles/clasificación , Mosquitos Vectores/parasitología , Mosquitos Vectores/fisiología , Malaria/transmisión , Malaria/epidemiología , Malaria/parasitología , Humanos , Prevalencia , Plasmodium/aislamiento & purificación , Plasmodium/clasificación , Plasmodium/fisiología , Bovinos , Femenino , Culex/parasitología , Culex/fisiologíaRESUMEN
Copper metal ions (Cu2+) are widely used in various industries, and their salts are used as supplementary components in agriculture and medicine. As this metal ion is associated with various health issues, it is necessary to detect and monitor it in environmental and biological samples. In the present report, we synthesized a naphthoquinoline-dione-based probe 1 containing three ester groups to investigate its ability to detect metal ions in an aqueous solution. Among various metal ions, probe 1 showed a vivid color change from yellow to colorless in the presence of Cu2+, as observed by the naked eye. The ratiometric method using the absorbance ratio (A413/A476) resulted in a limit of detection (LOD) of 1 µM for Cu2+. In addition, the intense yellow-green fluorescence was quenched upon the addition of Cu2+, resulting in a calculated LOD of 5 nM. Thus, probe 1 has the potential for dual response toward Cu2+ detection through color change and fluorescence quenching. 1H-NMR investigation and density functional theory (DFT) calculations indicate 1:1 binding of the metal ion to the small cavity of the probe comprising four functional groups: the carbonyl group of the amide (O), the amino group (N), and two t-butyl ester groups (O). When adsorbed onto various solid surfaces, such as cotton, silica, and filter paper, the probe showed effective detection of Cu2+ via fluorescence quenching. Probe 1 was also useful for Cu2+ sensing in environmental samples (sea and drain water) and biological samples (live HeLa cells).
RESUMEN
Nanotechnology has significantly transformed cancer treatment by introducing innovative methods for delivering drugs effectively. This literature review provided an in-depth analysis of the role of nanocarriers in cancer therapy, with a particular focus on the critical concept of the 'stealth effect.' The stealth effect refers to the ability of nanocarriers to evade the immune system and overcome physiological barriers. The review investigated the design and composition of various nanocarriers, such as liposomes, micelles, and inorganic nanoparticles, highlighting the importance of surface modifications and functionalization. The complex interaction between the immune system, opsonization, phagocytosis, and the protein corona was examined to understand the stealth effect. The review carefully evaluated strategies to enhance the stealth effect, including surface coating with polymers, biomimetic camouflage, and targeting ligands. The in vivo behavior of stealth nanocarriers and their impact on pharmacokinetics, biodistribution, and toxicity were also systematically examined. Additionally, the review presented clinical applications, case studies of approved nanocarrier-based cancer therapies, and emerging formulations in clinical trials. Future directions and obstacles in the field, such as advancements in nanocarrier engineering, personalized nanomedicine, regulatory considerations, and ethical implications, were discussed in detail. The review concluded by summarizing key findings and emphasizing the transformative potential of stealth nanocarriers in revolutionizing cancer therapy. This review enhanced the comprehension of nanocarrier-based cancer therapies and their potential impact by providing insights into advanced studies, clinical applications, and regulatory considerations.
Asunto(s)
Antineoplásicos , Portadores de Fármacos , Nanopartículas , Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Portadores de Fármacos/química , Nanopartículas/química , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacocinética , Antineoplásicos/química , Animales , Sistemas de Liberación de Medicamentos/métodos , Nanomedicina/métodos , Liposomas , Micelas , Distribución TisularRESUMEN
A survey of Ixodid tick species diversity on domestic ruminants was conducted in seven agro-climatic regions of Tamil Nadu State, India. Tick surveys were conducted on domestic ruminants such as cattle, buffalo, sheep, and goat in seven districts of Tamil Nadu. The overall tick infestation was 38.8%, 5.8%, 14.6%, and 40.8% on cattle, buffaloes, sheep, and goats, respectively. A total of 8068 ticks from 18 species belonging to four genera were recorded. Overall, Haemaphysalis intermedia was the predominant (51.38%) tick species which has a wide host range. The most prevalent tick species in cattle and buffalo were Rhipicephalus (B.) microplus (25.41%) and Rhipicephalus haemaphysaloides (56.69%), respectively. Haemaphysalis intermedia was the most prevalent in ticks in sheep (70.35%), goat (70.35%), and dog (55.79%). In the present study, local anomalies such as the ectromely of one leg and the absence of adanal plates were observed in Rh. haemaphysaloides. The study also found that local anomaly such as protuberances in the hind tarsal and atrophy of the adanal plate was observed in Rhipicephalus (Boophilus) microplus. In addition, a general anomaly with three atrophy caudal appendages was also observed in Rhipicephalus (Boophilus) microplus. The overall prevalence of anomalies in Rh. haemaphysaloides and Rh. (B.) microplus was 0.3% (3/971) and 0.4% (3/678), respectively.