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Lung cancer is still a global health challenge in terms of high incidence, morbidity, and mortality. Recent scientific studies have determined that pyroptosis, a highly inflammatory form of programmed cell death, can be identified as a potential lung cancer therapeutic target. The NLRP3 inflammasome acts as a critical mediator in this process and, upon activation, activates multiprotein complex formation as well as caspase-1 activation. This process, triggered by a release of pro-inflammatory cytokines, results in pyroptotic cell death. Also, the relationship between the NLRP3 inflammasome and lung cancer was justified by its influence on tumour growth or metastasis. The molecular pathways produce progenitive mediators and remake the tissue. Finally, targeting NLRP3 inflammasome for pyroptosis induction and inhibition of its activation appears to be a promising lung cancer treatment approach. This technique makes cancer treatment more promising and personalized. This review explores the role of NLRP3 inflammasome activation and its possibilities in lung cancer treatment.
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Inflamasomas , Neoplasias Pulmonares , Proteína con Dominio Pirina 3 de la Familia NLR , Piroptosis , Humanos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Piroptosis/fisiología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Inflamasomas/metabolismo , AnimalesRESUMEN
Background: Metabolic syndrome consists of cardiometabolic risk factors that promote the development of atherosclerotic cardiovascular disease, type 2 'DM' and obesity. These are associated with increased cardiovascular mortality and morbidity. Metabolic disorders (MD) are becoming more prevalent both in developing countries and developed countries and are now considered as lifestyle diseases. In women of reproductive age group, especially pregnancy, the blood glucose level is increasing which adversely affects the health of mother and child. Similarly, high blood pressure also precipitates the problems. This study was carried out to find the prevalence of hypertension, diabetes mellitus, obesity and 'MD' among the women living in remote rural set-up. Materials and Methods: This cross-sectional study was done among women of reproductive age group in 15 villages from 5 panchayats of field practice area of Maharishi Markandeshwar Medical College and Hospital, Kumarhatti, Solan. They were screened for 'MD' through investigative procedures (weight, height, BMR, abdominal girth, blood pressure through sphygmomanometer, blood glucose through the glucometer method), serum HDL and triglycerides. Respondents from the family were asked about the common/general information of house. The tool used for collecting general and relevant information from the respondent was a questionnaire, which was pretested for validity before being used in the field. Results: Four-hundred and sixty-seven women of reproductive age group participated in the study. Half of the participants were with qualification of matriculate and 9.2% participants were illiterate. Three-fourths of the participants were married women and 89% were vegetarian. Sixty-four per cent of participants were housewives. Half of the participants had a normal BMI, whereas 28.9% were overweight and 10% were obese. The prevalence of hypertension and diabetes among the participants were 12.5% and 9.8%, respectively. Forty-seven per cent participants had a waist circumference above 80 cm. Conclusion: The level of non-communicable diseases is related with the MD which has the adverse effect on the various systems and organs of the subjects. The MD can be controlled with the certain changes in the life style pattern. The GOI is also concerned with such scenarios in the country. It is recommended that women of reproductive age group undergo regular blood pressure and blood sugar screenings to detect hypertension and diabetes early and take appropriate measures to manage them.
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An environment of physically linked, technologically networked things that can be found online is known as the "Internet of Things." With the use of various devices connected to a network that allows data transfer between these devices, this includes the creation of intelligent communications and computational environments, such as intelligent homes, smart transportation systems, and intelligent FinTech. A variety of learning and optimization methods form the foundation of computational intelligence. Therefore, including new learning techniques such as opposition-based learning, optimization strategies, and reinforcement learning is the key growing trend for the next generation of IoT applications. In this study, a collaborative control system based on multiagent reinforcement learning with intelligent sensors for variable-guidance sections at various junctions is proposed. In the future generation of Internet of Things (IoT) applications, this study provides a multi-intersection variable steering lane-appropriate control approach that uses intelligent sensors to reduce traffic congestion at many junctions. Since the multi-intersection scene's complicated traffic flow cannot be accommodated by the conventional variable steering lane management approach. The priority experience replay algorithm is also included to improve the efficiency of the transition sequence's use in the experience replay pool and speed up the algorithm's convergence for effective quality of service in the upcoming IoT applications. The experimental investigation demonstrates that the multi-intersection variable steering lane with intelligent sensors is an appropriate control mechanism, successfully reducing queue length and delay time. The effectiveness of waiting times and other indicators is superior to that of other control methods, which efficiently coordinate the strategy switching of variable steerable lanes and enhance the traffic capacity of the road network under multiple intersections for effective quality of service in the upcoming IoT applications.
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Internet de las Cosas , Inteligencia Artificial , Inteligencia , Algoritmos , InternetRESUMEN
INTRODUCTION: Discrimination and stigma associated with epilepsy in schools impact the academic and mental aptitude of children with epilepsy. Teachers pre-sensitized to seizures exhibit a positive attitude along with better knowledge about epilepsy. The aim was to assess the impact of an interactive one-day educational workshop regarding epilepsy on the prevalent knowledge, attitude, and practices toward epilepsy among school teachers. METHODS: Conducted in December 2021 in a tertiary care teaching hospital of rural background in Northern India, this cross-sectional study included school teachers from government schools of Faridkot district of Punjab. The intervention consisted of a one-day interactive workshop on epilepsy and school health consisting of 100 minutes of lectures (4 lectures each of 25 minutes), 60 minutes of role plays, and 20 minutes of active discussion with participants (5 minutes after each session). The lectures were prepared using World Health Organization's Mental Health Gap (WHO's mhGAP) guidelines and elucidated knowledge regarding epilepsy and skills to provide first aid to seizures. School teachers were assessed on a pre and post-test structured questionnaire to assess their knowledge of, attitude, and practices regarding epilepsy before and immediately after the intervention. RESULTS: Two hundred and thirty teachers participated and the majority were from government primary schools, mean age was 43 ± 7 years and females (n = 121,53%) outnumbered males. Commonly reported sources of information regarding epilepsy by school teachers were family and friends (n = 91,40%) followed by social (n = 82, 36%) and public media (n = 81,35%), and the least common were doctors (n = 56,24%) and healthcare workers (n = 29, 13%). Fifty-six percent (n = 129) had witnessed seizures in either a stranger(n = 84,37%), family, or friend (n = 31,13%) and student of their class(n = 14,6%). Post-educational intervention, significant improvement was seen in the knowledge of and attitude regarding epilepsy including recognizing subtle features of epilepsy like blank stare (pre/post = 5/34) and transient change in behavior (pre/post = 16/32), non-contagiousness of epilepsy (pre/post = 158/187)and belief that children with epilepsy have normal intelligence (pre/post = 161/191) and a significant decrease in a number of teachers who thought that they need more time and attention in class (pre/post = 181/131). Post-educational sessions, significantly more number of teachers would allow children with epilepsy in their classroom (pre/post = 203/227), follow correct ways to provide first aid for seizures, and would allow their participation in all extracurricular activities even in high-risk outdoor games like swimming (pre/post = 4/36) and deep sea diving (pre/post = 7/18). CONCLUSION: The educational intervention had a positive impact on the knowledge, practices, and attitude regarding epilepsy but had a few, unexpected reverse effects as well. A single workshop may not be aptly adequate to provide accurate information regarding epilepsy. Sustained efforts in this direction are needed at the national and global level to develop the concept of "Epilepsy Smart Schools".
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Epilepsia , Maestros , Masculino , Femenino , Niño , Humanos , Adulto , Persona de Mediana Edad , Conocimientos, Actitudes y Práctica en Salud , Estudios Transversales , Epilepsia/psicología , Convulsiones , Instituciones Académicas , Encuestas y CuestionariosRESUMEN
The Internet of Vehicles (IoV) communication key management level controls the confidentiality and security of its data, which may withstand user identity-based attacks such as electronic spoofing. The IoV group's key is updated with a defined frequency under the current key management method, which lengthens the time between crucial changes and encryption. The cluster key distribution management is used as the study object in this paper, which is based on the communication security on the Internet of Vehicles cluster. When vehicles enter and exit the cluster, the Internet of Vehicles must update the group key in real-time to ensure its forward and backward security. A low-latency IoV group key distribution management technology based on reinforcement learning is proposed to optimize the group owner vehicle according to factors such as changes in the number of surrounding vehicles and essential update records and the update frequency and the key length of its group key. The technology does not require the group leader vehicle to predict the nearby traffic flow model. The access-driven cache attack model reduces the delay of encryption and decryption and is verified in the simulation of the IoV based on advanced encryption standards. The simulation results show that, compared with the benchmark group key management scheme, this technology reduces the transmission delay of key updates, the calculation delay of encryption and decryption of the IoV, and improves the group key confidentiality.
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Nube Computacional , Seguridad Computacional , Algoritmos , Confidencialidad , InternetRESUMEN
Weighted MR images of 421 patients with nasopharyngeal cancer were obtained at the head and neck level, and the tumors in the images were assessed by two expert doctors. 346 patients' multimodal pictures and labels served as training sets, whereas the remaining 75 patients' multimodal images and labels served as independent test sets. Convolutional neural network (CNN) for modal multidimensional information fusion and multimodal multidimensional information fusion (MMMDF) was used. The three models' performance is compared, and the findings reveal that the multimodal multidimensional fusion model performs best, while the two-modal multidimensional information fusion model performs second. The single-modal multidimensional information fusion model has the poorest performance. In MR images of nasopharyngeal cancer, a convolutional network can precisely and efficiently segment tumors.
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Procesamiento de Imagen Asistido por Computador , Neoplasias Nasofaríngeas , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/diagnóstico por imagen , Redes Neurales de la Computación , Tomografía Computarizada por Rayos X/métodosRESUMEN
BACKGROUND: Gestational diabetes mellitus (GDM) is an increasing health issue among pregnant women worldwide. Treatment of hyperglycemia during pregnancy improves outcomes for both mothers and infants. Effectively performing and reviewing self-monitoring of blood glucose is time-consuming for patients and care providers. In the modern era, most people having access to smartphones create opportunities for use of phone-based technologies to improve patient care in chronic diseases. This review aims to investigate the awareness and use of the smartphone application (app) with respect to management of GDM among pregnant women. MATERIALS AND METHODS: Various relevant studies (n = 522) from 3 databases named Pub Med, Cochrane Library, and Google Scholar were included. For this, the study involved designing of a 5-stage review framework, which included research question identification, identification of articles, article selection, data collection, and result reporting. RESULTS: Initial search criteria used a combination of keywords, by which we found out 522 literatures from 3 databases. After screening the titles and abstracts, 249 articles were excluded due to duplicate literatures and 252 articles were excluded due to the following reasons: not relevant (n = 172), editorial (n = 43), not in English (n = 7), and abstract only (n = 30). Furthermore, 10 articles were excluded because apps such as MobiGuide, pregnant + app, and GDm health were not mentioned in these articles. A total of 11 articles were included for the final analysis. CONCLUSION: The mobile apps described in the present study (pregnant +, MobiGuide, and GDm health) provided personalized health care services, patient care improvement, and enhanced patient's compliance toward blood glucose monitoring and treatment.
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Diabetes Gestacional , Glucemia , Automonitorización de la Glucosa Sanguínea , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/terapia , Femenino , Humanos , Embarazo , Mujeres Embarazadas , TecnologíaRESUMEN
Background: Rhino-orbito-cerebral-mucormycosis (ROCM) associated with COVID-19 infection was at its peak during and immediately after the second wave of the pandemic in India during 2021. Many of the risk factors were implicated in the development of this deadly fungal infection, when there was a sudden surge of cases, especially who had a history of COVID-19 infection. Objectives: The objective of the study was to describe the characteristic magnetic resonance imaging (MRI) findings in invasive mucormycosis and to evaluate the extent and severity of invasive mucormycosis. Materials and Methods: A retrospective study was carried out for 4 months which included 60 patients who underwent MRI using a Siemens Avanto 1.5 Tesla scanner. During our study, 68 cases were selected based on clinicoradiological features suspected of ROCM. However, 8 patients were excluded on the basis of exclusion criteria as either there was no definitive evidence of COVID infection or were proven to be negative for mucormycosis on microbiological examination. Results: On the basis of the spectrum of MRI findings, post-COVID-19 related ROCM was broadly categorized into three stages. Out of total of 60 patients, the disease was localized to the nasal and paranasal sinus region (Stage I) in 7 patients (11.66%), extending to adjacent extrasinus orofacial soft tissue structures (Stage II) in 36 patients (60%), and intracranial extension of disease (Stage III) was seen in 17 patients (28.33%). Conclusion: In post-COVID-19 patients presenting with clinical features suspected of ROCM, MRI imaging helps in early diagnosis and staging/severity of ROCM, so that timely intervention can be planned to reduce mortality as well as morbidity.
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The emergence of multi drug resistance in non-small cell lung cancer (NSCLC) patients is a major challenge towards the efficacy of chemotherapy. Thus, there is an urgent need for the newer, better clinically targeted strategies to treat this disease. Earlier studies from our laboratory revealed the apoptotic activity of Maackia amurensis agglutinin (MAA) in human NSCLC cells. In this study, the effect of MAA on drug resistant NSCLC cells was investigated. Two Paclitaxel-resistant NSCLC sub-lines (A549/PTX100 and NCI-H460/PTX100) were developed from A549 & NCI-H460 cell lines respectively. The generation of drug resistance phenotype was confirmed by the expression of cell surface MDR-1. Both the drug resistant sub-lines showed distinct morphological alterations. MAA interacted with the cell-surface protein(s) of apparent Mr ~66 kDa and induced apoptosis in both the sub-lines through intrinsic/mitochondrial pathway, involving reduction in mitochondrial trans-membrane potential, up-regulation of Bax, unaltered/decreased expression of Bcl-XL, release of mitochondrial cytochrome c into the cytosol and activation of pro-caspases (-9&-3). Our findings highlighted the potential of this plant agglutinin to serve as an apoptosis inducing agent in drug resistant NSCLC cells.
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Aglutininas/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Maackia/química , Células A549 , Aglutininas/química , Apoptosis/efectos de los fármacos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Caspasas/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Proteína bcl-X/genéticaRESUMEN
Premature graying of hair has major psychosocial and socioeconomic repercussion, as it is considered as a sign of hastily progressing old age, ill health and often leads to loss of self-esteem. Hair is said to gray prematurely when it happens before the age of 20 years in Caucasians, 25 years in Asians, and 30 years in Africans. The hair color chiefly depends on melanin pigment, and fabrication of this pigment takes place in melanosomes through the process of melanogenesis. This complex biochemical pathway (melanogenesis) is further dependent on tyrosinase which acts as fuel.The normal human scalp is subjected to various factors categorized as intrinsic and extrinsic leading to graying of hair. Intrinsic factors comprise of variants responsible for changes at genetic level while extrinsic factors include air pollution, ultraviolet radiation, smoking, and nutrition. It has been proposed that direct or indirect effect of all these factors results in the generation of reactive oxygen species (ROS), thus leading to further damage. Though research has expanded in last few years in terms of microscopic, biochemical (hormonal, enzymatic), and molecular changes happening within hair follicle/shaft, still the exact mechanism leading to premature graying of hair is not well understood. Probable solutions toward this quandary are diet, herbal remedies, and temporary hair colorants. Ironically, the latter one being the most common has various side effects such as allergic reactions, inflammation, and hair loss. The aim of this paper was to review the manifestation and probable future interventions in preventing premature hair graying.
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PURPOSE: Enteroaggregative Escherichia coli (EAEC) is an emerging enteric pathogen causing diarrhoeal diseases in multiple epidemiological and clinical settings. However, understanding of the pathogenesis of the disease caused by this organism is still suboptimal. Studies have indicated that enteric bacteria induced cell cycle arrest and apoptosis in host intestinal epithelial cells might play a vital role in the pathogenesis caused by these organisms. In this study an attempt was made to assess EAEC-induced apoptosis and cell cycle modulation in human intestinal epithelial cell lines. METHODOLOGY: INT-407 and HCT-15 cells were infected with EAEC-T8 (clinical isolate) as well as plasmid cured variant of EAEC-T8 (EAEC-pT8). Propidium iodide staining was done to select the time of infection and the incubation period of the infected culture. Apoptosis was further assessed in EAEC infected both the cell lines by annexin-V-FLUOS & propidium iodide, cell death detection ELISA, DNA strand breaks and microscopic analysis. Further, the DNA content of the EAEC-infected cells at different phases of cell cycle was also monitored. RESULTS: We have found that EAEC could induce apoptosis in human small intestinal as well as colonic epithelial cell lines, which was assessed by the expression of phosphatidylserine on host cell surface, internucleosomal cleavage of host cell DNA and microscopic analysis of the characteristic apoptotic features of these cells. EAEC was also found to arrest cells at S phase and G2-M phase of the cell cycle. CONCLUSIONS: EAEC-T8 could induce maximum apoptosis and cell cycle modulation in both small intestinal and colonic epithelial cells. Further, we have observed that the plasmid of this organism had maximum contribution to these processes. The outcome of this study has undoubtedly led to a better understanding of the basic mechanism of pathogenesis caused by EAEC.
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Apoptosis , Puntos de Control del Ciclo Celular , Células Epiteliales/microbiología , Escherichia coli/patogenicidad , Adhesión Bacteriana , Línea Celular Tumoral , Células Epiteliales/citología , Infecciones por Escherichia coli/microbiología , Humanos , Intestinos/citología , Fosfatidilserinas/metabolismo , Plásmidos/metabolismoRESUMEN
Anthelmintic activity of both ethanolic and aqueous extracts of Calotropis procera flowers, Azadirachta indica leaves and Punica granatum fruit peel in comparison with albendazole was evaluated through in vitro studies by the worm motility inhibition assay. Significant anthelmintic effects (p < 0.0005) were observed on live Gastrothylax indicus worm as evident from their mortality at 4 h post exposure to both ethanolic and aqueous extracts. Phytochemical analysis of extracts revealed the presence of phenols, alkaloids, saponins, tannins, flavonoids, steroids and triterpenoids. LC-50 values were determined to be 12.05 mg/ml ± 3.24 and 23.52 mg/ml ± 6.4 for C. procera, 24.37 mg/ml ± 4.11 and 21.02 mg/ml ± 4.6 for A. indica, 18.92 mg/ml ± 4.54 and 24.43 mg/ml ± 6.96 for P. granatum ethanolic and aqueous extracts respectively, whereas it was 29.23 µg/ml ± 4.51 for albendazole. The mean mortality index (MI) was 1.0 and 0.90 for C. procera, 0.90 for A. indica and 0.73 and 0.80 for P. granatum ethanolic and aqueous extracts respectively whereas for albendazole it was 1.0. Percent mean worm motility inhibition (%WMI) was observed to be between 70 and 100 % for different extracts.Various concentrations (5-5000 µg/ml) of all the plant extracts and albendazole were used to detect their cytotoxic effects against HeLa cell line to determine CC-50 by MTT assay. CC-50 values, of all the plant extracts were determined to be >1000 µg/ml and for albendazole it was found to be >10 µM. All the three plants can be potential sources for novel anthelmintics.
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Maackia amurensis agglutinin (MAA) is gaining recognition as the potential diagnostic agent for cancer. Previous studies from our laboratory have demonstrated that this lectin could interact specifically with the cells and biopsy samples of non-small cell lung cancer (NSCLC) origin but not with normal lung fibroblast cells. Moreover, this lectin was also found to induce apoptosis in NSCLC cells. Further, the biological activity of this lectin was shown to survive gastrointestinal proteolysis and inhibit malignant cell growth and tumorigenesis in mice model of melanoma thereby indicating the therapeutic potential of this lectin. Paclitaxel is one of the widely used traditional chemotherapeutic drugs for treatment of NSCLC but it exerts side-effects on normal healthy cells too. Studies have revealed that lectins have potential to act as an adjuvant chemotherapeutic agent in cancer of different origin. Thus, in the present study, an attempt was made to assess the chemo-adjuvant role of MAA in three types of NSCLC cell lines [adenocarcinoma cell line (A549), squamous cell carcinoma cell line (NCI-H520) and large cell carcinoma cell line (NCI-H460)]. We have observed that the non-cytotoxic concentration of this lectin was able to enhance the cytotoxic activity of Paclitaxel even at low dose by inducing apoptosis through intrinsic/mitochondrial pathway in all the three types of NSCLC cell lines, although the involvement of extrinsic pathway of apoptosis in case of NCI-H460 cell line could not be ruled out. Further, this lectin was also found to augment the chemo-preventive activity of this drug by arresting cells in G2-M phase of the cell cycle. Collectively, our results have suggested that Maackia amurensis agglutinin may have the potential to be used as adjuvant chemotherapeutic agent in case of NSCLC.
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Aglutininas/farmacología , Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Maackia/química , Paclitaxel/farmacología , Aglutininas/metabolismo , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Sinergismo Farmacológico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Lectinas de Plantas/metabolismoRESUMEN
This study was conducted to enhance flavor characteristics of wine by malolactic fermentation using recombinant Pediococcus acidilactici BD16 (fcs (+)/ech (+)) encoding synthetic genes of feruloyl-CoA synthetase and enoyl-CoA hydratase. After malolactic fermentation, wine phenolics were characterized using LCMS-ESI technique and a significant improvement in the antioxidant activity and flavor characteristics of wine was observed due to increased concentration of cinnamic acid derivatives. This proof of concept study highlights the role of recombinant P. acidilactici BD16 (fcs (+)/ech (+)) in improving flavor as well as aroma of wine due to production of several phenolic derivatives during secondary fermentation. A novel metabolic pathway was predicted from mass spectral analysis data that indicates biotransformation of cinnamic acid and derivatives into apigenin, catechin, coniferyl aldehyde, cyanidin, hydroxybenzoic acids, laricitrin, luteolin, malvidin 3-glucoside, myricetin, naringenin, pelargonin, piceatannol, querecitin, and vanillin that not only increased the overall consumer appreciation but also improved nutritional and probably the therapeutic properties of wines. This is a first evidence-based study where role of recombinant P. acidilactici BD16 (fcs (+)/ech (+)) in the wine secondary fermentation has been elucidated.
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Pediococcus/genética , Pediococcus/metabolismo , Vino/análisis , Antioxidantes/metabolismo , Benzaldehídos/análisis , Cinamatos/metabolismo , Citrus sinensis , Coenzima A Ligasas/genética , Coenzima A Ligasas/metabolismo , Enoil-CoA Hidratasa/genética , Enoil-CoA Hidratasa/metabolismo , Fermentación , Microbiología de Alimentos/métodos , Redes y Vías Metabólicas , Fenoles/análisis , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Rosa , Espectrometría de Masa por Ionización de Electrospray , Vitis , Vino/microbiologíaRESUMEN
The rapidly increasing global population has bowed the attention of family planning and associated reproductive health programmes in the direction of providing a safe and reliable method which can be used to limit family size. The world population is estimated to exceed a phenomenal 10 billion by the year 2050 A.D., thus presenting a real jeopardy of overpopulation with severe implications for the future. Despite the availability of contraceptive methods, there are over one million elective abortions globally each year due to unintended pregnancies, having devastating impact on reproductive health of women worldwide. This highlights the need for the development of newer and improved contraceptive methods. A novel contraceptive approach that is gaining substantial attention is "immunocontraception" targeting gamete production, gamete outcome, or gamete function. Amongst these, use of sperm antigens (gamete function) seems to be an exciting and feasible approach. However, the variability of immune response and time lag to attain titer among vaccinated individuals after active immunization has highlighted the potential relevance of preformed antibodies in this league. This review is an attempt to analyze the current status and progress of immunocontraceptive approaches with respect to their establishment as a future fertility control agent.
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Anticoncepción Inmunológica , Anticoncepción , Vacunas Anticonceptivas , Animales , Humanos , Inmunización PasivaRESUMEN
PURPOSE: Association of Escherichia coli with its detrimental action on spermatozoa is well established in vitro. Therefore, an attempt was made to clarify the effect of presence of E. coli in Balb/c mouse vagina on fertility outcome. MATERIALS AND METHODS: All the mice in experimental groups received intravaginal administration of either spermagglutinating E. coli, PBS or standard E. coli strain (MTCC 1687; non-spermagglutinating/spermimmobilizing). Different doses and durations of administration were 10(4), 10(6), or 10(8) cfu for 10 consecutive days; 10(4) or 10(6) for 3 consecutive days. Subgroups were created to evaluate cytokine level in reproductive organ and histopathological changes in both reproductive and non-reproductive organs. RESULTS: All the animals receiving either 10(4), 10(6) or 10(8) cfu of spermagglutinating E. coli for 3 or 10 consecutive days were rendered infertile in contrast to groups receiving PBS or standard strain (MTCC 1687) of E. coli. Another group of mice receiving spermagglutinating E. coli when mated after the clearance of organism from mouse vagina under natural circumstances or with use of antibiotic remained fertile. No other clinical manifestation could be seen apparently or histologically, except minor rise in IL-10 level and mild leukocyte infiltration in vagina of animals inoculated with spermagglutinating E. coli. CONCLUSIONS: Our data suggests that presence of spermagglutinating strain of E. coli in vagina/vaginal tract might be playing significant role in fertility outcome.
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Infecciones por Escherichia coli/complicaciones , Escherichia coli/fisiología , Infertilidad/etiología , Aglutinación Espermática , Estructuras Animales/patología , Animales , Citocinas/análisis , Modelos Animales de Enfermedad , Femenino , Histocitoquímica , Masculino , Ratones Endogámicos BALB C , Vagina/microbiologíaRESUMEN
In an earlier work done in our laboratory, we have been able to isolate a sperm agglutinating strain of Escherichia coli from the semen sample of a male attending infertility clinic. Further, factor responsible for sperm agglutination (SAF) was isolated and purified, and, using SAF as a tool, corresponding SAF binding receptor from human spermatozoa has been purified. Characterization of SAF and SAF binding receptor using MALDI-TOF showed homology to glutamate decarboxylase and MHC class I molecule, respectively. Coincubation of SAF with spermatozoa not only resulted in spermagglutination but could also compromise other sperm parameters, namely, Mg(2+) dependent ATPase activity and apoptosis. Intravaginal administration of SAF could lead to infertility in Balb/c mice. SAF induced impairment of sperm parameters, and infertility was observed to be due to interaction of SAF with sperm surface receptor component as, when purified receptor was introduced, receptor completely inhibited all the detrimental effects induced by SAF. From these results, it could be concluded that interaction of SAF with spermatozoa is receptor mediated.
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Glutamato Descarboxilasa/genética , Infertilidad Masculina/genética , Complejo Mayor de Histocompatibilidad/genética , Aglutinación Espermática/genética , Adenosina Trifosfatasas/metabolismo , Animales , Apoptosis/genética , Escherichia coli/química , Escherichia coli/metabolismo , Glutamato Descarboxilasa/metabolismo , Humanos , Infertilidad Masculina/metabolismo , Masculino , Ratones , Unión Proteica , Semen/metabolismo , Espermatozoides/metabolismo , Espermatozoides/patología , Staphylococcus aureusRESUMEN
OBJECTIVE: To examine the receptor-ligand interaction between E. coli and spermatozoa resulting in sperm immobilization. METHODS: Sperm immobilization factor (SIF) was isolated and purified from filtrate of E. coli suspension. Receptor on human spermatozoa for SIF was made to isolated and purified by salt extraction, gel permeation and ion exchange chromatography. Receptor dependent immobilization of spermatozoa by SIF was confirmed by competitive inhibition by addition of the purified receptor and binding to sperm receptor by Fluorescin Isothiocynate (FITC) labelled SIF using fluorescence microscopy. RESULTS: Heat labile, non-dialyzable, sperm immobilization factor of â¼56 kDa was isolated and purified from E. coli. Using SIF as a tool, receptor of 113 kDa could be isolated and purified from human spermatozoa. Addition of purified receptor completely inhibited sperm immobilization and death induced by SIF suggesting receptor-dependent immobilization of spermatozoa. Further incubation of sperm with FITC labelled SIF resulted in staining of whole sperm. CONCLUSION: The study provides evidence of receptor-ligand interaction between E. coli and spermatozoa.
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Factores Biológicos/farmacología , Escherichia coli/química , Motilidad Espermática/efectos de los fármacos , Factores Biológicos/aislamiento & purificación , Humanos , MasculinoRESUMEN
Sperm agglutinating factor (SAF) isolated from Staphylococcus aureus when applied at concentration 10 µg before mating completely prevented conception in the mouse. The objective of the present study was to evaluate its safety, as safety is an important concern to be addressed before a compound is selected for contraceptive use. Our results showed that SAF has a very high safety profile. Vaginal application of SAF at 10 µg to the mouse for 14 consecutive days caused no systemic toxicity and vaginal irritation as indicated by lack of effect on organ weights and histology. Moreover, no adverse effect was observed on the subsequent reproductive capability, perinatal outcome and growth and development of the offspring. SAF (10 µg) did not irritate the skin or penile mucosa. Oral administration of 2 mg/kg body weight of SAF did not show any toxicity to reproductive and non-reproductive organs. Therefore, SAF with spermicidal activity and lack of toxicity may have the potential to become the active ingredient of a vaginal contraceptive.
Asunto(s)
Aglutinación Espermática , Espermicidas/farmacología , Staphylococcus aureus , Vagina/efectos de los fármacos , Administración Intravaginal , Animales , Femenino , Tamaño de la Camada , Masculino , Ratones , Ratones Endogámicos BALB C , Espermicidas/administración & dosificación , Espermicidas/toxicidad , Pruebas de Toxicidad , Resultado del Tratamiento , Vagina/patologíaRESUMEN
AIM: To explore the influence of Escherichia coli on the motility of human spermatozoa and its possible mechanism. METHODS: Highly motile preparations of spermatozoa from normozoospermic patients were coincubated with Escherichia coli for 4 hours. At 1, 2 and 4 hours of incubation, sperm motility was determined. The factor responsible for sperm immobilization without agglutination was isolated and purified from filtrates. RESULTS: This report confirms the immobilization of spermatozoa by E. coli and demonstrates sperm immobilization factor (SIF) excreted by E. coli. Further this factor was purified by ammonium sulfate precipitation, gel permeation chromatography, and ion-exchange chromatography. Purified SIF (56 kDa) caused instant immobilization without agglutination of human spermatozoa at 800 microg/mL and death at 2.1 mg/mL. Spermatozoa incubated with SIF revealed multiple and profound alterations involving all superficial structures of spermatozoa as observed by scanning electron microscopy. CONCLUSION: In conclusion, these results have shown immobilization of spermatozoa by E. coli and demonstrate a factor (SIF) produced and secreted by E. coli which causes variable structural damage as probable morphological correlates of immobilization.