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1.
Indian J Med Res ; 158(5&6): 542-551, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-38088421

RESUMO

BACKGROUND OBJECTIVES: Smokeless tobacco (SLT) product consumption has profound public health implications for its users. The p H and moisture of SLTs determine the bioavailability of nicotine, the microbial structure dynamics and the amount of microbial conversion of tobacco alkaloids to carcinogenic tobacco-specific nitrosamines. This study aimed to characterize and compare the p H, moisture and alkaloid content of various SLT products. METHODS: Thirty-seven SLT samples including khaini , snus, moist snuff, gul , pan masala , zarda , Mainpuri kapoori and qiwam were collected from the retail market around the National Capital Region in north India and their p H, moisture, nicotine and alkaloid content were measured. The p H and total nicotine were used to calculate the amount of free nicotine, the readily absorbed form, for each product by applying the Henderson-Hasselbalch equation. RESULTS: The investigation showed that the SLTs varied drastically in their p H (5.36 to 10.27), moisture content (4.7 to 51.7%) and alkaloid content (0.82 to 35.87 mg/g). The p H and free nicotine levels of a product were found to be positively correlated, and the highest free nicotine content was reported in snus samples. Further, the moisture content was seen to impact the bacterial and fungal diversity in these samples. INTERPRETATION CONCLUSIONS: Studies to detect the presence of pathogenic microbiological genera as well as potentially toxic constituents are warranted. The use of SLTs as an alternative to cigarette smoking should be discouraged, and cessation programmes must call attention to their detrimental effects and emphasize on benefits of quitting SLT consumption.


Assuntos
Alcaloides , Estimulantes do Sistema Nervoso Central , Nitrosaminas , Tabaco sem Fumaça , Índia , Nicotina
2.
Appl Microbiol Biotechnol ; 107(12): 4009-4024, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37154908

RESUMO

Smokeless tobacco (SLT) is certainly one of the major risk factors associated with oral cancer. Disruption of oral microbiota-host homeostasis contributes to the progression of oral cancer. Here, we profiled SLT users' oral bacterial composition and inferred their functions by sequencing 16S rDNA V3-V4 region and PICRUSt2, respectively. Oral bacteriome of SLT users (with or without oral premalignant lesions), SLT with alcohol co-users, and non-SLT consumers were compared. Oral bacteriome is shaped primarily by SLT use and the incidence of oral premalignant lesions (OPL). A significantly increased bacterial α-diversity was monitored in SLT users with OPL compared to in SLT users without OPL and non-users, whereas ß-diversity was significantly explained by OPL status. Overrepresented genera were Prevotella, Fusobacterium, Veillonella, Haemophilus, Capnocytophaga, and Leptotrichia in SLT users having OPL. LEfSe analysis identified 16 genera as a biomarker that were differentially abundant in SLT users having OPL. The functional prediction of genes significantly increased for several metabolic pathways, more importantly, were nitrogen metabolism, nucleotide metabolism, energy metabolism, and biosynthesis/biodegradation of secondary metabolites in SLT users having OPL. Furthermore, HPV-16 and EBV, but not HPV-18, were considerably connected with the SLT users having OPL. Overall, this study provides evidence that SLT utilization and OPL development are associated with oral bacteriome dysbiosis indicating the enrichment of bacterial species known for their contribution to oral carcinogenesis. Therefore, delineating the cancer-inducing bacterial population in SLT users will facilitate the future development of microbiome-targeted therapies. KEY POINTS: • SLT consumption significantly elevates oral bacterial diversity. • Prevalent significant genera are Prevotella, Veillonella, and Haemophilus in SLT users with OPL. • SLT promotes the occurrence of the cancer-inducing bacterial population.


Assuntos
Neoplasias Bucais , Tabaco sem Fumaça , Humanos , Tabaco sem Fumaça/efeitos adversos , Neoplasias Bucais/etiologia , Uso de Tabaco/efeitos adversos , Uso de Tabaco/epidemiologia , Consumo de Bebidas Alcoólicas , Incidência
3.
Curr Microbiol ; 80(4): 131, 2023 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-36894760

RESUMO

Smokeless tobacco products (STPs) contain several microbial communities which are responsible for the formation of carcinogens, like tobacco-specific nitrosamine (TSNAs). A majority of STPs are sold in loose/unpackaged form which can be loaded with a diverse microbial population. Here, the fungal population and mycotoxins level of three popular Indian loose STPs, Dohra, Mainpuri Kapoori (MK), and loose leaf-chewing tobacco (LCT) was examined using metagenomic sequencing of ITS1 DNA segment of the fungal genome and LC-MS/MS, respectively. We observed that Ascomycota was the most abundant phylum and Sterigmatomyces and Pichia were the predominant fungal genera in loose STPs. MK displayed the highest α-diversity being enriched with pathogenic fungi Apiotrichum, Aspergillus, Candida, Fusarium, Trichosporon, and Wallemia. Further, FUNGuild analysis revealed an abundance of saprotrophs in MK, while pathogen-saprotroph-symbiotroph were abundant in Dohra and LCT. The level of a fungal toxin (ochratoxins A) was high in the MK product. This study caution that loose STPs harbor various harmful fungi that can infect their users and deliver fungal toxins or disrupt the oral microbiome of SLT users which can contribute to several oral pathologies.


Assuntos
Micobioma , Micotoxinas , Tabaco sem Fumaça , Tabaco sem Fumaça/análise , Tabaco sem Fumaça/microbiologia , Cromatografia Líquida , Espectrometria de Massas em Tandem
4.
Indian J Pediatr ; 90(8): 761-765, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-35737182

RESUMO

OBJECTIVE: To evaluate the proportion of patients who received empirical treatment with antitubercular therapy (ATT) prior to the diagnosis of Hodgkin lymphoma (HL) in the first multicentric, prospective study on HL from India, and to assess its impact on extent of disease at diagnosis and outcomes. METHODS: Children < 18 y with biopsy proven HL were enrolled in InPOG-HL-15-01. Along with other clinical and epidemiological data, history of prior treatment with ATT was documented. All patients received treatment as per a risk-stratified, response-adapted strategy. RESULTS: Out of 396, 115 (29%) children had received ATT prior to establishing a definitive diagnosis of HL. This cohort presented with advanced-stage disease (p = 0.001) and B symptoms (p = 0.001) in a higher proportion of cases. Consequently, those children were more likely to receive 6 rather than 4 cycles of chemotherapy (p = 0.001). They were more likely to have infradiaphragmatic involvement (p = 0.001). Overall survival and event-free survival were not different. CONCLUSION: Empirical treatment with ATT in children presenting with lymphadenopathy continues to be practiced widely in India. The delay in diagnosis may contribute to children presenting with advanced-stage disease warranting more intensive treatment for successful outcomes.


Assuntos
Doença de Hodgkin , Linfadenopatia , Criança , Humanos , Estudos Prospectivos , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/tratamento farmacológico , Antituberculosos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfadenopatia/tratamento farmacológico
5.
Appl Microbiol Biotechnol ; 106(17): 5643-5657, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35913514

RESUMO

Smokeless tobacco (SLT) alters the oral microbiome of smokeless tobacco users. Dysbiosis of oral bacteriome has been determined; however, the mycobiome of SLT users has not been characterized. The oral mycobiome was assayed by amplification and sequencing of the fungal internal transcribed spacer (ITS1) region from oral swab samples of non-SLT users, SLT users (with or without oral lesions), and SLT with alcohol users. We observed that the richness and diversity of oral mycobiome were significantly decreased in SLT with oral lesions users than in non-users. The ß-diversity analysis showed significant dissimilarity of oral mycobiome between non-users and SLT with oral lesions users. Linear discriminant analysis effect size and random forest analysis of oral mycobiome affirm that the genus Pichia was typical for SLT with oral lesions users. Prevalence of the fungal genus Pichia correlates positively with Starmerella, Mortierella, Fusarium, Calonectria, and Madurella, but is negatively correlated with Pyrenochaeta, Botryosporium, and Alternaria. Further, the determination of oral mycobiome functionality showed a high abundance of pathotroph-saprotroph-symbiotroph and animal pathogen-endophyte-epiphyte-undefined saprotroph at trophic and guild levels, respectively, indicating possibly major changes in normal growth repression of types of fungi. The oral mycobiome in SLT users was identified and comprehensively analyzed for the first time. SLT intake is associated with oral mycobiome dysbiosis and such alterations of the oral mycobiome may contribute to oral carcinogenesis in SLT users. This study will provide a basis for further large-scale investigations on the potential role of the mycobiome in SLT-induced oral cancer. KEY POINTS: • SLT induces dysbiosis of the oral microbiome that can contribute to oral cancer. • Oral mycobiome diversity is noticeably reduced in SLT users having oral lesions. • Occurrence of Pichia can be used as a biomarker for SLT users having oral lesions.


Assuntos
Neoplasias Bucais , Micobioma , Tabaco sem Fumaça , Disbiose , Humanos , Projetos Piloto , Uso de Tabaco
6.
Microbiol Spectr ; 10(4): e0227321, 2022 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-35695566

RESUMO

The microbial communities present in smokeless tobacco products (STPs) perform critical steps in the synthesis of carcinogens, mainly tobacco-specific nitrosamines (TSNAs). Most studies emphasize the bacterial component, and the mycobiome of STPs has not been well characterized. In this study, we investigated the fungal communities in the different categories of STPs by sequencing the internal transcribed spacer (ITS) rRNA region of the fungal genome. The ecological character of the fungal community associated with STPs was determined by using FUNGuild. Our results indicated that Ascomycota and Basidiomycota were the most abundant fungal phyla across all STPs. The predominant fungal genera in STPs were Pichia, Sterigmatomyces, and Mortierella. The α-diversity varied significantly across the STPs based on observed, Fisher, and Shannon indices. Using SparCC cooccurrence network analysis, significant positive correlations of 58.5% and negative connections of 41.5% were obtained among fungal genera identified in STPs. Furthermore, the functional predictions by FUNGuild determined that STPs possessed high abundances of saprotroph and pathotroph-saprotroph-symbiotroph fungal trophic groups. At the functional guild level, the qiwam samples contained high abundances of soil saprotrophs, while plant pathogens were prevalent in pan-masala samples. These results suggest that various fungal populations reside in STPs and interrelate with each other and can contribute to the synthesis of TSNAs. This study has established the basis for future large-scale investigations of STP-associated mycobiota and the impact of such mycobiota in oral carcinogenesis in STP users via inflammation and carcinogens (TSNAs and mycotoxins). IMPORTANCE Smokeless tobacco products (STPs) contain complex microbial communities that influence the synthesis of carcinogens, such as tobacco-specific nitrosamines (TSNAs). Research on STP-associated bacterial populations revealed connections between bacterial metabolism and TSNA synthesis. The abundance of the fungal population may also have an impact on the production of TSNAs. This study examined STPs popularly used in India, and diverse fungal communities were identified in these STPs. Pichia, Sterigmatomyces, and Mortierella were the predominant fungal genera in the STPs. High abundances of saprotroph and pathotroph-saprotroph-symbiotroph trophic groups in STPs could affect the degradation of tobacco products and the synthesis of TSNAs.


Assuntos
Micobioma , Nitrosaminas , Tabaco sem Fumaça , Bactérias/genética , Carcinógenos/análise , Índia , Nitrosaminas/análise , Tabaco sem Fumaça/análise
7.
J Cell Biochem ; 123(9): 1422-1439, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35765708

RESUMO

Carcinogens present in smokeless tobacco (SLT) like tobacco-specific nitrosamines can be metabolized by the cytochrome P450 (CYP450) enzyme. Functionally, the CYP450 enzyme resides in a heme pigment to perform the catalytic activity. The CYP1A1 is one of the main extrahepatic CYP450 enzymes known to detoxify toxic substances and activate carcinogens. The CYP1A1 inhibition by potential inhibitors reduce the chance of oral cancer. The current study aimed to explore more about the inhibitor binding site and identification of lead alkaloids, that could work as putative inhibitors against target CYP1A1. In respect, we have performed docking studies, virtual screening of alkaloids, and natural product libraries against CYP1A1 followed by molecular dynamic simulations and binding free energy calculations. Docking studies of tobacco-specific nitrosamine (TSNA) products and their similar carcinogen analogs revealed that the heme group is bound to the floor of the bowl-shaped cavity whereas carcinogens are bound to the roof of the rounded shape cavity. Furthermore, virtual screening and binding free energy calculations revealed Tomatidine as a putative inhibitor against CYP1A1. On the basis of altogether outcomes of the current study, we have concluded that the addition of lead-hit alkaloid Tomatidine and others in SLT products may be working as a supplement that could be able to reduce the expression of human CYP1A1 and suppresses carcinogenic by-products formations.


Assuntos
Alcaloides , Produtos Biológicos , Nitrosaminas , Alcaloides/farmacologia , Carcinógenos , Citocromo P-450 CYP1A1/química , Citocromo P-450 CYP1A1/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Heme , Humanos , Simulação de Dinâmica Molecular
8.
Appl Microbiol Biotechnol ; 106(11): 4129-4144, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35604437

RESUMO

Smokeless tobacco product (STP) consumption is a significant public health threat across the globe. STPs are not only a storehouse of carcinogens and toxicants but also harbor microbes that aid in the conversion of tobacco alkaloids to carcinogenic tobacco-specific nitrosamines (TSNAs), thereby posing a further threat to the health of its consumers. The present study analyzed the bacterial diversity of popular dry and loose STPs by 16S rRNA gene sequencing. This NGS-based investigation revealed four dominant phyla Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria and identified 549 genera, Prevotella, Bacteroides, and Lactobacillus constituting the core bacteriome of these STPs. The most significantly diverse bacteriome profile was displayed by the loose STP Mainpuri kapoori. The study further predicted the functional attributes of the prevalent genera by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) algorithm. Genes encoding for nitrate and nitrite reduction and transport enzymes, antibiotic resistance, multi-drug transporters and efflux pumps, secretion of endo- and exotoxin, and other pro-inflammatory molecules were identified. The loose STPs showed the highest level of nitrogen metabolism genes which can contribute to the synthesis of TSNAs. This study reveals the bacteriome of Indian domestic loose STPs that stagger behind in manufacturing and storage stringencies. Our results raise an alarm that the consumption of STPs harboring pathogenic genera can potentially lead to the onset of several oral and systemic diseases. Nevertheless, an in-depth correlation analysis of the microbial diversity of STPs and their elicit impact on consumer health is warranted. KEY POINTS: • Smokeless tobacco harbors bacteria that aid in synthesis of carcinogenic nitrosamines. • Most diverse bacteriome profile was displayed by loose smokeless tobacco products. • Pathogenic genera in these products can harm the oral and systemic health of users.


Assuntos
Nitrosaminas , Tabaco sem Fumaça , Bactérias/metabolismo , Carcinógenos/metabolismo , Índia , Nitrosaminas/análise , Nitrosaminas/metabolismo , Filogenia , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Tabaco sem Fumaça/microbiologia
9.
Pediatr Blood Cancer ; 68(10): e29219, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34291860

RESUMO

BACKGROUND: Hodgkin lymphoma (HL) in childhood is an eminently curable disease. Excellent outcomes can be achieved even in resource-limited settings and increasingly, the focus is on limiting long-term toxicity. Contemporary treatment incorporates a risk-stratified, response-adapted approach using multiagent chemotherapy with or without low-dose radiotherapy (RT). Many developing countries continue to use ABVD (adriamycin, bleomycin, vinblastin, and dacarbazine)-based regimen owing to limited acute toxicity, cost, and ease of delivery. We report outcomes of children with early-stage HL using limited cycles of ABVD-based treatment in the first prospective multicentric collaborative study from India InPOG-HL-15-01. METHODS: Children <18 years with biopsy-proven HL were enrolled. Patients with stages I and IIA with or without bulky disease were classified as having early-stage disease. Patients were planned to receive four cycles of ABVD subject to satisfactory early response assessment (ERA) scheduled after two cycles of chemotherapy. RT was limited to patients with bulky disease or those with suboptimal ERA. RESULTS: Four hundred ten patients were enrolled over 30 months from 27 centers. One hundred thirty-four were classified as having early-stage disease. Fifty-three (40%) of these had bulky disease. One hundred ten (83%) of this cohort achieved complete or very good partial ERA. Fifty-four (40%) received RT. At a median of 52 months since diagnosis, 5-year event-free survival (EFS) and overall survival (OS) is 94% and 95.5%, respectively. Treatment-related mortality and abandonment were <1%. CONCLUSION: Limited cycles of ABVD with RT to selected patients is a very effective option for patients with early-stage disease in resource-limited settings.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Doença de Hodgkin , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/administração & dosagem , Criança , Dacarbazina/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Humanos , Estadiamento de Neoplasias , Estudos Prospectivos , Resultado do Tratamento , Vimblastina/administração & dosagem
10.
Anaerobe ; 70: 102400, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34090995

RESUMO

Smokeless tobacco products possess a complex community of microorganisms. The microbial community ferment compounds present in the smokeless tobacco products and convert them into carcinogens like tobacco-associated nitrosamines. However, the potential of smokeless tobacco products associated bacteriome to manipulate systemic inflammation and other signaling pathways involved in the etiology of oral cancer will be a risk factor for oral cancer. Further, damage to oral epithelial cells causes a leaky oral layer that leads to increased infiltration of bacterial components like lipopolysaccharide, flagellin, and toxins, etc. The consumption of smokeless tobacco products can cause damage to the oral layer and dysbiosis of oral microbiota. Hence, the enrichment of harmful microbes due to dysbiosis in the oral cavity can produce high levels of bacterial metabolites and provoke inflammation as well as carcinogenesis. Understanding the complex and dynamic interrelation between the smokeless tobacco-linked bacteriome and host oral microbiome may help to unravel the mechanism of oral carcinogenesis stimulated by smokeless tobacco products. This review provides an insight into smokeless tobacco product-associated bacteriome and their potential in the progression of oral cancer. In the future, this will guide in the evolution of prevention and treatment strategies against smokeless tobacco products-induced oral cancer. Besides, it will assist the government organizations for better management and cessation policy building for the worldwide problem of smokeless tobacco addiction.


Assuntos
Bactérias/isolamento & purificação , Microbiota , Neoplasias Bucais/etiologia , Boca/microbiologia , Tabaco sem Fumaça/efeitos adversos , Animais , Bactérias/classificação , Bactérias/genética , Humanos , Neoplasias Bucais/microbiologia , Tabaco sem Fumaça/análise
11.
CNS Neurol Disord Drug Targets ; 20(6): 540-555, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33687903

RESUMO

BACKGROUND: Human health issues caused by Cigarette Smoke Carcinogens (CSC) are increasing rapidly every day and challenging the scientific community to provide a better understanding in order to avoid its impact on communities. Cigarette smoke also contains tobacco-based chemical compounds harmful to human beings, either smokers or non-smokers. OBJECTIVE: We have tested 7H-Dibenzo[c,g]carbazole (7H-DBC) and Dibenz[a,h]acridine (DBAD) derivatives of Asz-arenes along with N'-Nitrosoanabasine (NAB) and N-Nitrosoanatabine (NAT) derivatives of N-Nitrosamines molecular interaction with CNS biomolecules. METHODS: Computational synergistic approaches like system biology and molecular interaction techniques were implemented to conduct the analysis. RESULTS: CSC efficiently interacted with NRAS, KRAS, CDH1, and RAC1 molecular targets in CNS. We have also performed the interactome analysis followed by system biology approaches and found that HSPA8 is the most important hub protein for the network generated for CSC-hampered genes of CNS. We have also identified 6 connector proteins, namely TP53, HSP90AA1, PPP2CA, CDH1, CTNNB1, and ARRB1. Further analysis revealed that NRAS and CDH1 have maximum interactions with all the selected CSC. CONCLUSION: The obtained structural analysis data could be utilized to assess the carcinogenic effect of CSC and could be useful in the treatment of CNS diseases and disorders induced, especially by tobacco-specific carcinogens, or it could also be used in vivo/ in vitro experimentation model designing.


Assuntos
Carcinógenos/metabolismo , Sistema Nervoso Central/metabolismo , Nicotiana/metabolismo , Fumaça , Humanos , Nitrosaminas , Proteína Fosfatase 2 , Produtos do Tabaco
12.
Front Microbiol ; 12: 784841, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35003015

RESUMO

Smokeless tobacco products (STPs) carry assorted microbial population that contributes to carcinogens synthesis like tobacco-specific nitrosamines (TSNAs). Extensive exploration of microbiota-harboring STPs is required to understand their full carcinogenic potential. Here, we applied 16S rRNA gene sequencing to investigate bacteriome present in moist STPs immensely consumed in India (Khaini, Moist-snuff, Qiwam, and Snus). Further, the functional metagenome was speculated by PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) to assign the abundance of genes related to nitrogen metabolism, bacterial toxins, antibiotic drug resistance and other pro-inflammatory molecules. Highly diverse bacterial communities were observed in all moist STPs. Taxonomic analysis revealed a total of 549 genera belonging to four major phyla Proteobacteria, Firmicutes, Bacteroidetes and Actinobacteria. Overall, the core bacterial genera Acinetobacter, Bacillus, Prevotella, Acetobacter, Lactobacillus, Paracoccus, Flavobacterium, and Bacteroides were significantly abundant in moist STPs. Elevated moisture-holding products like Moist-snuff and Qiwam harbor rich bacterial species diversity and showed similar bacteriome composition. Furthermore, Qiwam products showed the highest level of genes associated with nitrogen metabolism, antibiotic resistance, toxins, and pro-inflammation (predicted by PICRUSt) which can contribute to the synthesis of TSNAs and induction of oral cancer. The present broad investigation of moist STPs-associated bacteriome prevalence and their detailed metabolic potential will provide novel insight into the oral carcinogenesis induced by STPs.

13.
Autoimmunity ; 53(7): 385-393, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32924613

RESUMO

The depletion of gut mucosal barrier enables exposure of gut microbes/gut microbial products to the host mucosal immunity which may increase the risk of metabolic/inflammatory disorders. These immune responses can lead to the development of mild autoimmunity to metabolic peptides coming from gut bacteria and may result in metabolic diseases like late-onset diabetes (LOD). In the present study, we identified host sera cross-reactivity with gut bacterial peptides similar to host proteins. The interaction between diabetic sera and gut peptides was detected by enzyme-linked immunosorbent assay (ELISA) and results were confirmed using surface plasmon resonance (SPR). The ELISA assay showed a higher level of serum cross-reactivity in LOD patients as compared to non-diabetic controls against three peptides (P-5, P-9, and P-13). SPR analysis confirmed binding-affinity against P-5 and P-13. Also, a significant correlation was observed between inflammatory markers and P-5. This study demonstrates that gut health is important not only for intestinal diseases but also for several late-onset diseases, like, diabetes.


Assuntos
Antígenos de Bactérias/imunologia , Autoantígenos/imunologia , Autoimunidade , Diabetes Mellitus Tipo 2/etiologia , Microbioma Gastrointestinal/imunologia , Peptídeos/imunologia , Biomarcadores , Diabetes Mellitus Tipo 2/metabolismo , Suscetibilidade a Doenças , Ensaio de Imunoadsorção Enzimática , Humanos , Mediadores da Inflamação , Ressonância de Plasmônio de Superfície
14.
Immunol Lett ; 223: 71-77, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32360573

RESUMO

Biosurfactants (BSs) molecules are classically branded as emulsifiers of hydrocarbon compounds and are extensively applied in several fields including pharmaceutics, food processing, biodegradation, bioremediation, cosmetics, and pest control management. Due to the amphiphilic and surface-active properties, BS interacts with lipid membranes of the cell and alters its physio-chemical nature. As a result, various biological functions of the target cells are lost. In recent times, several studies have shown antimicrobial, antiviral, and anticancer potentials of BS molecules. BS primarily destroy bacterial cells by directly disrupting the integrity of the plasma membrane or cell wall. Whereas, their antiviral action seems to be due to their physicochemical interaction with the virus lipid envelope. However, antiproliferative potency of BSs make them a potential anticancer agent. BS can induce cell cycle arrest, apoptosis and metastasis arrest in tumour cells with no influence on non-tumour cells. Interestingly, BS molecules also demonstrate immunomodulatory activities either by suppression or activation of immune system. The advantages of BS over their chemical counterparts are their biocompatibility, high biodegradability, high specificity and low toxicity. Moreover, chemical diversity, environmentally friendly nature and, suitability for large-scale production has bestowed BS many future applications. This review presents, in a systematic manner, the interference of BS of various classes including glycolipids, phospholipids and lipopeptides with the activities or mechanism of action of immune response. Also, we shed lights on how such biological activities of BSs make them a new class of therapeutic molecules for combating various immune disorders.


Assuntos
Materiais Biocompatíveis/uso terapêutico , Produtos Biológicos/uso terapêutico , Doenças do Sistema Imunitário/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Tensoativos/uso terapêutico , Animais , Humanos , Imunidade , Terapia de Imunossupressão , Metabolismo dos Lipídeos
15.
Cancer Med ; 8(1): 246-260, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30575301

RESUMO

Cancer is one of the major health problem globally, responsible for high morbidity and mortality. Exposure of humans to xenobiotics is associated with the development of cancer. Further, these xenobiotics may combine with the body proteins and can act as a hapten and elicit an antibody response. In this study, we examined whether the regular exposer to xenobiotics evokes anti-xenobiotic antibodies and the presence of these antibodies have any correlation with the prevention of cancer. Interestingly, we noticed that the healthy household contacts showed significantly greater titers of anti-xenobiotic antibodies, as compared to cancer patients. Consequently, suggesting that the higher level of anti-xenobiotic antibodies may be responsible for neutralizing the effect of xenobiotics in the healthy subjects. Thereby, preventing the individuals from disease. In contrast, the presence of a significantly lower level of anti-xenobiotic antibodies in the cancer patients may be a causative factor for disease infliction. In conclusion, immunotherapy employing anti-xenobiotic antibodies may provide a prudent remedial measure to clear xenobiotics from the body of the individuals and thereby protecting from cancer.


Assuntos
Anticorpos/sangue , Haptenos/imunologia , Neoplasias/epidemiologia , Exposição Ocupacional , Xenobióticos/imunologia , Feminino , Humanos , Índia/epidemiologia , Masculino , Neoplasias/sangue , Neoplasias/imunologia , Risco
16.
Indian J Orthop ; 52(5): 554-560, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30237614

RESUMO

BACKGROUND: Supracondylar humerus fracture is the most common fracture around elbow in children. Closed reduction and percutaneous Kirschner wire (pin) fixation is the standard method of managing displaced extension type (Gartland Type II and Type III) supracondylar humerus fractures. The configuration of wires is debatable. Although two crossed K-wires are mechanically stable, there is an inherent risk of ulnar nerve injury. Lateral K-wires - parallel or divergent - are good alternative. This study was aimed at identifying the best configuration for the lateral wires. MATERIALS AND METHODS: Patients with Gartland type 3 supracondylar humerus fractures were randomized by envelope method to receive closed reduction and K-wire fixation in either a parallel or divergent fashion. The patients were followed up at 3 weeks for wire removal and at 6 weeks and 3 months after surgery. Baumann's angle, functional outcome as per Flynn's criteria, and range of motion were recorded in each visit. Effect of delay in surgery was also evaluated as a secondary outcome. RESULTS: Nineteen patients received fixation with parallel wires and 11 patients had divergent fixation. No loss of reduction was seen in any patient at 3 months. No statistically significant difference was seen in the Baumann's angles and outcome according to Flynn's criteria irrespective of the wire configuration (divergent or parallel). Furthermore, the delay in surgery was also found not to have a significant effect on the functional outcome. CONCLUSIONS: Both parallel and divergent K-wire configurations provide satisfactory stability when accurate reduction and adequate fixation of the fracture has been done. Based on the limited number of patients in this study, one configuration cannot be judged to be superior to the other.

17.
Int J Nanomedicine ; 6: 2305-19, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22072868

RESUMO

BACKGROUND: Nanomaterials are considered to be the pre-eminent component of the rapidly advancing field of nanotechnology. However, developments in the biologically inspired synthesis of nanoparticles are still in their infancy and consequently attracting the attention of material scientists throughout the world. Keeping in mind the fact that microorganism-assisted synthesis of nanoparticles is a safe and economically viable prospect, in the current study we report Candida albicans-mediated biological synthesis of gold nanoparticles. METHODS AND RESULTS: Transmission electron microscopy, atomic force microscopy, and various spectrophotometric analyses were performed to characterize the gold nanoparticles. The morphology of the synthesized gold particles depended on the abundance of C. albicans cytosolic extract. Transmission electron microscopy, nanophox particle analysis, and atomic force microscopy revealed the size of spherical gold nanoparticles to be in the range of 20-40 nm and nonspherical gold particles were found to be 60-80 nm. We also evaluated the potential of biogenic gold nanoparticles to probe liver cancer cells by conjugating them with liver cancer cell surface-specific antibodies. The antibody-conjugated gold particles were found to bind specifically to the surface antigens of the cancer cells. CONCLUSION: The antibody-conjugated gold particles synthesized in this study could successfully differentiate normal cell populations from cancerous cells.


Assuntos
Candida albicans/metabolismo , Ouro/metabolismo , Neoplasias Hepáticas Experimentais/química , Neoplasias Hepáticas Experimentais/diagnóstico , Nanopartículas Metálicas/química , Animais , Anticorpos/química , Anticorpos/metabolismo , Biomimética , Sobrevivência Celular/efeitos dos fármacos , Citosol/química , Feminino , Ouro/química , Ouro/farmacocinética , Ouro/toxicidade , Células HeLa , Humanos , Macrófagos Peritoneais/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Microscopia de Força Atômica , Microscopia Eletrônica de Transmissão , Proteínas de Neoplasias/imunologia , Proteínas de Neoplasias/metabolismo , Tamanho da Partícula , Espectrofotometria
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