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BACKGROUND & OBJECTIVES: Dengue virus (DENV) is the causative agent of dengue fever (DF) and dengue hemorrhagic fever (DHF). It has four distinct serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) based on their antigenic properties. Mostly, the immunogenic epitopes are present in the envelope (E) protein of the virus. Heparan sulfate (HS) acts as a receptor and interacts with the E protein of the virus thus facilitating the entry of dengue virus into human cells. This study focuses on epitope prediction on the E protein of the DENV serotype. The non-competitive inhibitors of HS were designed using bioinformatics. METHODS: In the present study, epitope prediction of the E protein of DENV serotypes was performed using the ABCpred server and IEDB analysis resource. The interactions of HS and viral E proteins (PDB ID: 3WE1 and PDB ID:1TG8) were evaluated through AutoDock. Subsequently, non-competitive inhibitors were designed to bind the E protein of DENV better than HS. All the docking results were validated by re-docking the ligand-receptor complexes and superimposing them onto their co-crystallized complexes using AutoDock and visualizing them in Discovery Studio. RESULTS: The result predicted B-cell and T-cell epitopes on the E protein of DENV serotypes. The designed HS ligand 1 (non-competitive inhibitor) demonstrated potential binding with the DENV E protein, thereby inhibiting HS-E protein binding. The re-docked complexes were superimposed entirely onto the native co-crystallized complexes (low root mean square deviation values), which validates the docking protocols. INTERPRETATION & CONCLUSION: The identified B-cell and T-cell epitopes of the E protein and non-competitive inhibitors of HS (ligand 1) could be used in the designing of potential drug candidates against the dengue virus.
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Virus del Dengue , Dengue , Humanos , Anticuerpos Antivirales , Epítopos de Linfocito T , Ligandos , Proteínas del Envoltorio ViralRESUMEN
Intrinsic resistance to ionizing radiation is the major impediment in the treatment and clinical management of esophageal squamous cell carcinoma (ESCC), leading to tumor relapse and poor prognosis. Although several biological and molecular mechanisms are responsible for resistance to radiotherapy in ESCC, the molecule(s) involved in predicting radiotherapy response and prognosis are still lacking, thus requiring a detailed understanding. Recent studies have demonstrated an imperative correlation amongst several long non-coding RNAs and their involvement in complex cellular networks like DNA damage and repair, cell cycle, apoptosis, proliferation, and epithelial-mesenchymal transition. Additionally, accumulating evidence has suggested abnormal expression of lncRNAs in malignant tumor cells before and after radiotherapy effects in tumor cells' sensitivity. Thus, lncRNAs indeed represent unique molecules that can influence tumor cell susceptibility for various clinical interventions. On this note, herein, we have summarized the current status of lncRNAs in augmenting resistance/sensitivity in ESCC against radiotherapy. In addition, we have also discussed various strategies to increase the radiosensitivity in ESCC cells under clinical settings.
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Carcinoma de Células Escamosas de Esófago/radioterapia , ARN sin Sentido/genética , ARN Largo no Codificante/genética , ARN Neoplásico/genética , Daño del ADN , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/terapia , Regulación Neoplásica de la Expresión Génica , Terapia Genética , Humanos , MicroARNs/genética , Terapia Molecular Dirigida , ARN sin Sentido/uso terapéutico , ARN Largo no Codificante/uso terapéutico , Tolerancia a Radiación/genéticaRESUMEN
The importance of fungal infections in both human and animals has increased over the last decades. This article represents an overview of the different categories of fungal infections that can be encountered in animals originating from environmental sources without transmission to humans. In addition, the endemic infections with indirect transmission from the environment, the zoophilic fungal pathogens with near-direct transmission, the zoonotic fungi that can be directly transmitted from animals to humans, mycotoxicoses and antifungal resistance in animals will also be discussed. Opportunistic mycoses are responsible for a wide range of diseases from localized infections to fatal disseminated diseases, such as aspergillosis, mucormycosis, candidiasis, cryptococcosis and infections caused by melanized fungi. The amphibian fungal disease chytridiomycosis and the Bat White-nose syndrome are due to obligatory fungal pathogens. Zoonotic agents are naturally transmitted from vertebrate animals to humans and vice versa. The list of zoonotic fungal agents is limited but some species, like Microsporum canis and Sporothrix brasiliensis from cats, have a strong public health impact. Mycotoxins are defined as the chemicals of fungal origin being toxic for warm-blooded vertebrates. Intoxications by aflatoxins and ochratoxins represent a threat for both human and animal health. Resistance to antifungals can occur in different animal species that receive these drugs, although the true epidemiology of resistance in animals is unknown, and options to treat infections caused by resistant infections are limited.
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Farmacorresistencia Fúngica , Micosis/veterinaria , Micotoxicosis/veterinaria , Animales , Antifúngicos/uso terapéutico , Enfermedades Endémicas/veterinaria , Humanos , Micosis/tratamiento farmacológico , Micosis/microbiología , Micosis/transmisión , Micotoxinas/toxicidad , Infecciones Oportunistas/tratamiento farmacológico , Infecciones Oportunistas/microbiología , Infecciones Oportunistas/transmisión , Infecciones Oportunistas/veterinaria , Zoonosis/tratamiento farmacológico , Zoonosis/microbiología , Zoonosis/transmisiónRESUMEN
We describe Mus musculus castaneus as a new mammalian host for Cryptococcus neoformans var. grubii (VNI). Eighteen apparently healthy adults and pups of the rodent were collected from human dwellings in Varanasi, a city of India. Both clinical and behavioral examinations of the rodents did not reveal any sign of the disease. Among visceral organs, histological examination of only liver exhibited the presence of single celled, encapsulated, Southgate's mucicarmine positive fungal structures consistent with C. neoformans. Nevertheless, culture of tissue homogenates of brain, lungs, liver, and kidneys yielded white colonies on Sabouraud's dextrose agar and brown mucoid colonies of C. neoformans on Staib's and Tobacco agar media. The pathogen was isolated from habitat soil as well as fresh faeces of the animals. All isolates were urease positive, nitrate and canavanine-glycine bromothymol blue negative, exhibited phenoloxidase activity and grew at 37°C. The isolates were identified as C. neoformans var. grubii with ITS primers and unique marker (GACA)4. The pathogen when inoculated in immunosuppressed mice showed low pathogenicity. To our knowledge, we for the first time report case cluster of Mus musculus castaneus as new passenger host for C. neoformans var. grubii (VNI).
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Criptococosis/microbiología , Cryptococcus neoformans/aislamiento & purificación , Reservorios de Enfermedades/microbiología , Animales , Criptococosis/transmisión , Cryptococcus neoformans/clasificación , Cryptococcus neoformans/genética , Cryptococcus neoformans/patogenicidad , ADN de Hongos/genética , ADN Espaciador Ribosómico/genética , Heces/microbiología , Interacciones Huésped-Patógeno , Huésped Inmunocomprometido , India , Ratones , Técnicas de Tipificación Micológica , Reacción en Cadena de la Polimerasa , Microbiología del Suelo , VirulenciaRESUMEN
In present study free radical scavenging potential of aerial parts and root of Phyllanthus fraternus was investigated. Extraction was done in water and ethanol. Total antioxidant capacity was measured by DPPH free radical scavenging method; ethanolic extract of aerial part was most potent in activity with 50% inhibition at 258 µg/mL concentration. Lipid peroxidation (LPO) was measured in terms of thiobarbituric acid-reactive substances (TBARS) by using egg-yolk homogenates as lipid-rich media with EC50 of aerial part (ethanolic) 1522 µg/mL which was found to be most active. Superoxide (SO) radical scavenging activity was measured using riboflavin-light-nitroblue tetrazolium assay. Ethanolic and aqueous extract of both aerial part and root was almost similar in superoxide radical scavenging activity. Reducing power was determined on the basis of Fe³âº-Fe⺠transformation in the presence of extract. Total phenolic and flavonoid contents were also measured by spectroscopic method. Results showed that the ethanolic fraction of aerial part is most active towards antioxidant potential and this activity is related to its polyphenolic content and reducing potential. Thus, P. fraternus extract can be used as potent natural antioxidant.
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Antioxidantes/metabolismo , Depuradores de Radicales Libres/metabolismo , Phyllanthus/química , Componentes Aéreos de las Plantas/química , Extractos Vegetales/metabolismo , Raíces de Plantas/química , Análisis de Varianza , Antioxidantes/análisis , Antioxidantes/aislamiento & purificación , India , Peroxidación de Lípido , Oxidación-Reducción , Extractos Vegetales/análisis , Extractos Vegetales/aislamiento & purificación , EspectrofotometríaRESUMEN
Patients with impaired immune systems are particularly vulnerable to infections. With the increasing number of immunocompromised patients, it becomes necessary to design studies that evaluate the effects of toxic contaminants that are a part of our daily lives. Simultaneously, the management of these toxic components also becomes essential. Therefore, the present study evaluated the possible protective role of cinnamaldehyde (Cin) against tenuazonic acid-induced mycotoxicosis in the immunosuppressed murine model. Tenuazonic acid (TeA), a toxin usually produced by Alternaria species, is a common contaminant in tomato and tomato-based products. Evaluating the potential toxicity of a hazardous chemical necessitates the use of in vitro, in vivo, and in silico methods. Here, the immunomodulatory effect of TeA was assessed in vitro using mouse splenocytes. In silico docking was carried out for the tumour markers of eight organs and TeA. The haematological, histopathological, and biochemical aspects were analysed in vivo. The sub-chronic intoxication of mice with TeA showed elevated malondialdehyde, reduced catalase, and superoxide dismutase production, along with abnormal levels of aspartate aminotransferase and alanine transaminase. The treatment with Cin prevented TeA-induced alterations of antioxidant defense enzyme activities and significantly forbade TeA-induced organ damage, showing therapeutic effects and toxicity reduction in TeA-induced mycotoxicosis.
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Acroleína , Micotoxicosis , Ácido Tenuazónico , Animales , Acroleína/análogos & derivados , Acroleína/toxicidad , Acroleína/farmacología , Acroleína/química , Ratones , Ácido Tenuazónico/farmacología , Micotoxicosis/prevención & control , Micotoxicosis/tratamiento farmacológico , Modelos Animales de Enfermedad , Superóxido Dismutasa/metabolismo , Catalasa/metabolismo , Masculino , Huésped Inmunocomprometido , Malondialdehído/metabolismo , Simulación del Acoplamiento Molecular , Alternaria , Antioxidantes/farmacología , Antioxidantes/metabolismoRESUMEN
Introduction: This study was designed to assess the protective role of cinnamaldehyde (Cin) against the synergistic effect of tenuazonic acid (TeA) and Freund's adjuvant on different organs of Swiss albino mice. Methods: TeA was administered singly and in combination with Freund's adjuvant intra-peritoneally. The mice were divided into control (vehicle treated), mycotoxicosis-induced (MI) groups, and treatment groups. The route of administration of TeA was intra-peritoneal. The treatment group (FAICT) received Cin orally as a protective agent against TeA-induced mycotoxicosis. The effects on performance, differential leukocyte counts (DLC), and pathological measurements in eight organs (liver, lungs, kidney, spleen, stomach, heart, brain, and testis) were taken into consideration. Results: The body weight and feed consumption decreased significantly in the MI groups, which were reversed in the FAICT group. The necropsy observations revealed an increase in the relative organ-to-body weight percentage in the MI groups, which was restored to normal in the FAICT group. Freund's adjuvant enhanced the effects of TeA on DLC. The antioxidant enzymes SOD and CAT decreased, while MDA increased in the MI groups. Caspase-3 activity was reduced in all organs and remained stable in the treatment group. TeA elevated the ALT concentration in the liver and kidneys and the AST in the liver, kidney, heart, and brain tissues. The oxidative stress induced by TeA in the MI groups was ameliorated in the treatment group. Histopathological observations consisted of NASH, pulmonary oedema and fibrosis, renal crystals and inflammation, splenic hyperplasia, gastric ulceration and cyst, cerebral axonopathy, testicular hyperplasia, and vacuolation in the MI groups. However, no such pathology was recorded in the treatment group. Discussions: Thus, it can be concluded that the toxicity of TeA was found to be enhanced when combined with Freund's adjuvant. However, Cin exhibited promising protective effects against TeA + Freund's adjuvant toxicity and reverted the pathological alterations caused by them. Additionally, this study emphasizes Freund's adjuvant's ability to increase mycotoxicity rather than just acting as an immunopotentiator.
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Long non-coding RNAs have been demonstrated to promote proliferation and metastasis via regulating the miRNA/mRNA regulatory axis in various malignancies. Based on our preliminary study, we investigated the mechanism of LINC00324 through miR-493-5p/MAPK1 in esophageal squamous cell carcinoma (ESCC) pathogenesis. Herein, we confirmed that LINC00324 is significantly upregulated in ESCC primary cells and esophageal squamous cell carcinoma cell line KYSE-70. Silencing of LINC00324 modulates cell proliferation markers, p21, p27, c-Myc, and Cyclin D1 and epithelial-to-mesenchymal transition markers, slug, snail, ZEB1, vimentin, ZO-1, and E-cadherin protein expression in ESCC. Through bioinformatics and dual luciferase reporter assays, we identified miR-493-5p as the direct target molecule of LINC00324. We further revealed that LINC00324 negatively regulates miR-493-5p expression in ESCC. Moreover, our multiple gain-and loss-of-functional experiments proved that a combination of miR-493-5p and LINC00324 significantly rescued ESCC cell proliferation and metastatic phenotypes. Mechanistically, LINC00324 promotes ESCC pathogenesis by acting as a competing endogenous RNA and sponges miR-493-5p activity thereby activating MAPK1 during ESCC progression. We believe that targeting LINC00324 /miR-493-5p/MAPK1 axis may provide new therapeutic avenues for ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Sistema de Señalización de MAP Quinasas , MicroARNs , ARN Largo no Codificante , Humanos , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/metabolismo , Regulación Neoplásica de la Expresión Génica , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Transducción de Señal/genética , Sistema de Señalización de MAP Quinasas/genéticaRESUMEN
BACKGROUND: Radiation therapy leads to salivary gland damage that causes xerostomia, the standard radiation-induced complication during radiotherapy that affects the quality of life in head and neck cancer patients. This study was conducted at a tertiary cancer institute in Punjab state to analyze the influence of radiation therapy on various parameters and substances of saliva. MATERIALS AND METHODS: Sixty head and neck cancer patients who underwent conventional radiotherapy on a Cobalt machine were included. Saliva was collected in both stimulated and unstimulated states. Stimulated whole saliva was collected by applying two to three drops of citric acid solution (2%) over the dorsum of the tongue bilaterally at 30-s intervals for 2 min. Biochemical changes in the whole saliva were evaluated by biochemical methods at baseline, completion of therapy, and 3 and 6 months post-radiotherapy completion. RESULTS: The lowest concentration of proteins was seen after the therapy in unstimulated and stimulated saliva. Salivary protein levels showed a rising trend toward baseline in 3- and 6-month posttherapy samples. The peak value (0.4 mg/dl) was reached in the stimulated saliva after therapy. Salivary amylase did not show a consistent concentration graph. The salivary concentrations of sodium, potassium, and chloride showed peak values after radiotherapy. The lowest salivary pH was obtained at completion of therapy, both in unstimulated and stimulated saliva. After 3 months of chemoradiotherapy, the saliva reached a pH value of 8.3, whereas 6-month posttherapy sample showed a pH value of 8.4 in both unstimulated and stimulated saliva. CONCLUSIONS: At the completion of chemoradiotherapy, the total salivary protein, albumin, and inorganic components (calcium, magnesium, phosphorus) showed a downward trend from the baseline values due to the damage caused to the acinar part of the salivary gland by radiotherapy. The rise in salivary electrolytes' concentrations is attributed to the fact that even though there is loss of absorptive property of the tubular portion of the salivary gland, it retains its secretory property. Saliva becomes thick, scarce, tenacious, and acidic during the period of chemoradiotherapy.
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Neoplasias de Cabeza y Cuello , Traumatismos por Radiación , Xerostomía , Humanos , Saliva/química , Calidad de Vida , Xerostomía/diagnóstico , Xerostomía/etiología , Neoplasias de Cabeza y Cuello/radioterapia , Neoplasias de Cabeza y Cuello/complicaciones , Traumatismos por Radiación/complicaciones , Quimioradioterapia/efectos adversos , Proteínas y Péptidos Salivales/análisis , Proteínas y Péptidos Salivales/metabolismoRESUMEN
INTRODUCTION: SARS-CoV-2 has infected over 753 million individuals and caused more than 6.8 million deaths globally to date. COVID-19 disease severity has been associated with SARS-CoV-2 induced hyper inflammation and the immune correlation with its pathogenesis remains unclear. Acute viral infection is characterised by vigorous coordinated innate and adaptive activation, including an early cellular response that correlates well with the amplitude of virus specific humoral response. OBJECTIVE: The present study covers a wide spectrum of cellular immune response against COVID-19, irrespective of infection and vaccination. METHODS: We analysed immune status of (a) COVID-19 hospitalised patients including deceased and recovered patients, and compared with home isolated and non-infected healthy individuals, and (b) infected home isolated individuals with vaccinated individuals, using flow cytometry. We performed flow cytometry analysis of PBMCs to determine non-specific cell-mediated immune response. RESULTS: The immune response revealed extensive induction and activation of multiple immune lineages, including T and B cells, Th17 regulatory subsets and M1, M2 macrophages in deceased and hospitalised recovered patients, vaccinated and healthy individuals. Compromised immune cell expression was observed in deceased patients even in later stages, while expression was restored in hospitalised recovered patients and home isolated individuals. CONCLUSION: The findings associated with recovery and convalescence define a new signature of cellular immune response that persists in individuals with SARS-CoV-2 infection and vaccination. The findings will help in providing a better understanding of COVID-19 disease and will aid in developing better therapeutic strategies for treatment.
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COVID-19 , Humanos , Citometría de Flujo , SARS-CoV-2 , Linfocitos B , Vacunación , Inmunidad Celular , Anticuerpos AntiviralesRESUMEN
Immunohistochemistry (IHC) is a necessary ancillary technique in surgical pathology laboratories, particularly for oncology tissue specimens. Automation in the IHC technique has an advantage over manual methods in terms of quality, except for the cost of the equipment. Thus, the manual method of IHC staining is the preferred method of choice in countries with limited resources. However, standardization of all steps in the preanalytic phase is critical to obtain reliable immunohistochemistry test results. The current audit was conducted to describe the preanalytic factors affecting manual IHC methods. The most important preanalytic factors were fixative, the composition of dehydrate, pH, drying of sections, and heat-mediated antigen retrieval method (HMAR). The domestic pressure cooker method was found to be the best for HMAR.
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BACKGROUND: Despite the availability of advanced technology to detect and treat esophageal squamous cell carcinoma (ESCC), the 5-year survival rate of ESCC patients is still meager. Recently, long non-coding RNAs (lncRNAs) have emerged as essential players in the diagnosis and prognosis of various cancers. OBJECTIVE: This pilot study focused on identifying circulating lncRNAs as liquid biopsy markers for the ESCC. METHODOLOGY: We performed next-generation sequencing (NGS) to profile circulating lncRNAs in ESCC and healthy individuals' blood samples. The expression of the top five upregulated and top five downregulated lncRNAs were validated through quantitative real-time PCR (qRT-PCR), including samples used for the NGS. Later, we explored the diagnostic/prognostic potential of lncRNAs and their impact on the clinicopathological parameters of patients. To unravel the molecular target and pathways of identified lncRNAs, we utilized various bioinformatics tools such as lncRnome, RAID v2.0, Starbase, miRDB, TargetScan, Gene Ontology, and KEGG pathways. RESULTS: Through NGS profiling, we obtained 159 upregulated, 137 downregulated, and 188 neutral lncRNAs in ESCC blood samples compared to healthy individuals. Among dysregulated lncRNAs, we observed LINC00324 significantly upregulated (2.11-fold; p-value = 0.0032) and LOC100507053 significantly downregulated (2.22-fold; p-value = 0.0001) in ESCC patients. Furthermore, we found LINC00324 and LOC100507053 could discriminate ESCC cancer patients' from non-cancer individuals with higher accuracy of Area Under the ROC Curve (AUC) = 0.627 and 0.668, respectively. The Kaplan-Meier and log-rank analysis revealed higher expression levels of LINC00324 and lower expression levels of LOC100507053 well correlated with the poor prognosis of ESCC patients with a Hazard ratio of LINC00324 = 2.48 (95% CI: 1.055 to 5.835) and Hazard ratio of LOC100507053 = 4.75 (95% CI: 2.098 to 10.76)]. Moreover, we also observed lncRNAs expression well correlated with the age (>50 years), gender (Female), alcohol, tobacco, and hot beverages consumers. Using bioinformatics tools, we saw miR-493-5p as the direct molecular target of LINC00324 and interacted with the MAPK signaling pathway in ESCC pathogenesis. CONCLUSION: This pilot study suggests that circulating LINC00324 and LOC100507053 can be used as a liquid biopsy marker of ESCC; however, multicentric studies are still warranted.
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Cinnamaldehyde (Cin) is a natural product obtained from cinnamon and is reported to have a potential anti-fungal, anti-oxidant, anti-inflammatory and anticancer effect. The present study investigated the possible protective role of Cin against tenuazonic acid-induced mycotoxicity in the murine model. Tenuazonic acid (TeA), a toxin produced by Alternaria is a common contaminant in tomato and tomato-based products. Here, Swiss male mice were administered with TeA isolated from Paradendryphiella arenariae (MW504999) (source-tomato) through injection (238 µg/kg BW) and ingestion (475 µg/kg BW) routes for 2 weeks. Thereafter, the prophylaxis groups were treated with Cin (210 mg/kg BW). The experiment was carried out for 8 weeks. The treated groups were compared to the oral and intra-peritoneal experimental groups that received the toxin solely for 8 weeks. Haematological, histopathological and biochemical aspects of the experimental and the control mice were analysed. Sub-chronic intoxication of mice with TeA showed elevated malondialdehyde (MDA), reduced catalase (CAT) and superoxide dismutase (SOD) production; abnormal levels of aspartate transaminase (AST) and alanine transaminase (ALT). Treatment with Cin reversed TeA-induced alterations of antioxidant defense enzyme activities and significantly prevented TeA-induced organ damage. Thus, cinnamaldehyde showed therapeutic effects and toxicity reduction in TeA induced mycotoxicosis.
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Acroleína/análogos & derivados , Antioxidantes/farmacología , Ascomicetos/patogenicidad , Micosis/tratamiento farmacológico , Extractos Vegetales/farmacología , Ácido Tenuazónico/toxicidad , Acroleína/farmacología , Animales , Masculino , RatonesRESUMEN
Astroblastoma is a rare primary central nervous system tumor of controversial site of origin. They account for 0.45-2.8% of all primary neuroepithelial central nervous system. It has been reported in paediatric age group with bimodal age distribution affecting more females with male to female ratio being 1:11. Astroblastomas are controversial and challenging tumors in terms of diagnosis and therapeutics. Since it carries an unpredictable disease course it needs a regular follow up even for low grade tumor. Authors have tried various schedules of post op radiotherapy after maximum safe resection. Various chemotherapeutic drugs combination have also been tried without much success. We here report a 35 years old female patient who was diagnosed with high grade astroblastoma referred for post-operative radiotherapy after gross total resection. Since it is extremely rare tumor, its treatment still not well defined and also makes it difficult conduct studies to examine tumor characteristics.
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Dengue is the most common mosquito-borne viral infection in tropical and sub-tropical countries. In the recent years, frequent dengue outbreaks are being reported in many parts of India. DENV circulates as four independent serotypes posing a major public health threat around the globe. Phylogenetic and full genome sequence analyses of 19 complete DENV genome sequences presenting all the four serotypes in Pune, India (2016-2017) revealed no change in the circulating genotypes i.e., genotype V clade C (D1), genotype IVB (D2), genotype III lineage III (D3) and genotype I clade D (D4). Additionally, unique amino acid substitutions that may potentially influence viral fitness and virulence in host cells were identified. Mapping of the unique amino acid substitutions onto the T cell epitopes of the reference strains revealed that 8/10 (D1), 14/15 (D2), 3/4 (D3) and 21/74 (D4), amino acids were involved in T-cell epitope presentation for a maximum number of HLA alleles associated with disease outcome. Selection pressure analysis documented a positive selection pressure to be acting on few amino acid sites indicating continuous evolutionary changes in the viral RNA. Overall, the evolutionary and selection pressure data generated during this study may help in better understanding of DENV evolution and epidemiology.
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Virus del Dengue/genética , Evolución Molecular , Genoma Viral , Genotipo , Sustitución de Aminoácidos , India , Filogenia , Serogrupo , Secuenciación Completa del GenomaRESUMEN
Objective Cancer incidence across the geographical area is mercurial and factors like dietary habits, environment, social structure, genetics govern relative incidence. Malwa region of Punjab is one such geographical area of India speculated to have a higher incidence of cancer. The current analysis was done to assess the occurrence of cancer in the region and to analyze the trends and types of carcinoma with age, gender, site, and histopathological type, and to compare with the trends mentioned in the literature. Methods A retrospective analysis was done to collect and collate 2088 cancer patients' pathological records for three years at a tertiary treatment center. The collated data was digitized and used to create tables and histograms. Result Of the 2088 cancer cases, the leading cancer site was breast (24.7%) in females, followed by cancer of female genetic tract (18.9%), whereas in males, the most common site involved was head and neck (17.5%) followed by esophagus (10.3%). The leading cancer type for males was squamous cell carcinoma and for females was infiltrating ductal cell carcinoma. Breast carcinoma was most commonly seen cancer (40.5%) followed by female genital tract carcinoma and esophageal carcinoma in female patients. Whereas in males, head and neck carcinoma was most commonly identified (37.5%) followed by the gastrointestinal tract and esophageal carcinoma. This higher incidence may be attributed to better medical facilities, cancer awareness, and novel government schemes. Conclusion Based on our comprehensive analysis, we conclude that there was a change in trends of all types of carcinomas in males and females except breast carcinoma, which was seen as the most common carcinoma in female patients. Our findings suggest and support the strong implementation of cancer awareness programs and epidemiological studies to know the changing trends of risk factors in the region.
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Cryptococcosis is a potentially fatal fungal disease which has aggrandized with the emergence of AIDS and antifungal resistance. The currently used antifungals lack the broad-spectrum activity and result in several toxicities during long treatment regimens. Thus, the present study aims to evaluate the antifungal activity of cinnamaldehyde against Cryptococcus neoformans var. grubii, the etiological agent of the disease. Quantitative and qualitative in vitro fungal susceptibilities were carried out by minimum inhibitory concentration assay, flow cytometric analysis, and confocal microscopy. Micromorphological alterations were studied through scanning electron and light microscopies. "In vivo" antifungal efficacy of cinnamaldehyde was assessed. Cinnamaldehyde showed antifungal activity against C. neoformans in a dose-dependent manner. A concentration of 1.37 mg/mL of cinnamaldehyde was found to be inhibitory and fungicidal while the low concentration (0.68 mg/mL) was found to induce micromorphological changes and formation of giant/titan-like cells in this pathogen. The reparative activity of cinnamaldehyde and its ability to prolong the life even after the advent of cryptococcal meningitis in mice was also noticed. This study suggests potent anti-cryptococcal activity of cinnamaldehyde. Though, it has a couple of limitations like allergy and low bioavailability. However, these problems can be circumvented by developing suitable analogs of the compound. It, therefore, could be used as a therapeutic option against cryptococcosis and cryptococcal meningitis. Moreover, the evaluation of its pharmacokinetic and pharmacodynamic properties is desirable.