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1.
Drug Discov Today ; 29(7): 104053, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38849028

RESUMO

Pancreatic cancer (PC), a disease with high heterogeneity and a dense stromal microenvironment, presents significant challenges and a bleak prognosis. Recent breakthroughs have illuminated the crucial interplay among RAS, epidermal growth factor receptor (EGFR), and hedgehog pathways in PC progression. Small molecular inhibitors have emerged as a potential solution with their advantages of oral administration and the ability to target intracellular and extracellular sites effectively. However, despite the US FDA approving over 100 small-molecule targeted antitumor drugs, challenges such as low response rates and drug resistance persist. This review delves into the possibility of using small molecules to treat persistent or spreading PC, highlighting the challenges and the urgent need for a diverse selection of inhibitors to develop more effective treatment strategies.

2.
Arch Microbiol ; 206(7): 306, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38878076

RESUMO

In an age of cutting-edge sequencing methods and worldwide endeavors such as The Human Microbiome Project and MetaHIT, the human microbiome stands as a complex and diverse community of microorganisms. A central theme in current scientific inquiry revolves around reinstating a balanced microbial composition, referred to as "eubiosis," as a targeted approach for treating vast array of diseases. Vaginal Microbiota Transplantation (VMT), inspired by the success of fecal microbiota transplantation, emerges as an innovative therapy addressing vaginal dysbacteriosis by transferring the complete microbiota from a healthy donor. Antibiotics, while effective, pose challenges with adverse effects, high recurrence rates, and potential harm to beneficial Lactobacillus strains. Continued antibiotic usage also sparks worries regarding the development of resistant strains. Probiotics, though showing promise, exhibit inconsistency in treating multifactorial diseases, and concerns linger about their suitability for diverse genetic backgrounds. Given the recurrent challenges associated with antibiotic and probiotic treatments, VMT emerges as an imperative alternative, offering a unique and promising avenue for efficiently and reliably managing vaginal dysbiosis among a majority of women. This review critically evaluates findings from both animal and human studies, offering nuanced insights into the efficacy and challenges of VMT. An extensive analysis of clinical trials, provides a current overview of ongoing and completed trials, shedding light on the evolving clinical landscape and therapeutic potential of VMT. Delving into the origins, mechanisms, and optimized protocols of VMT, the review underscores the imperative for sustained research efforts to advance this groundbreaking gynecological therapy.


Assuntos
Disbiose , Microbiota , Probióticos , Vagina , Animais , Feminino , Humanos , Antibacterianos/uso terapêutico , Disbiose/microbiologia , Disbiose/terapia , Lactobacillus , Probióticos/administração & dosagem , Vagina/microbiologia
3.
Biomedicines ; 12(5)2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38791065

RESUMO

Hospital-acquired infections (HAIs) pose a significant risk to global health, impacting millions of individuals globally. These infections have increased rates of morbidity and mortality due to the prevalence of widespread antimicrobial resistance (AMR). Graphene-based nanoparticles (GBNs) are known to possess extensive antimicrobial properties by inflicting damage to the cell membrane, suppressing virulence, and inhibiting microbial biofilms. Developing alternative therapies for HAIs and addressing AMR can be made easier and more affordable by combining nanoparticles with medicinal plants harboring antimicrobial properties. Hence, this study was undertaken to develop a novel graphene-silver nanocomposite via green synthesis using Trillium govanianum plant extract as a reducing agent. The resulting nanocomposite comprised silver nanoparticles embedded in graphene sheets. The antibacterial and antifungal properties of graphene-silver nanocomposites were investigated against several nosocomial pathogens, namely, Candida auris, Candida glabrata, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The nanocomposite displayed broad-range antimicrobial potential against the test pathogens, with minimum inhibitory concentrations (MICs) ranging between 31.25 and 125.0 µg/mL, and biofilm inhibition up to 80-96%. Moreover, nanocomposite-functionalized urinary catheters demonstrated hemocompatibility towards sheep erythrocytes and imparted anti-fouling activity to the biomaterial, while also displaying biocompatibility towards HEK 293 cells. Collectively, this investigation highlights the possible application of green-synthesized GBNs as an effective alternative to conventional antibiotics for combating multidrug-resistant pathogens.

4.
Arch Microbiol ; 206(4): 158, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38480540

RESUMO

Quantum Dots (QDs) have emerged as versatile nanomaterials with origins spanning organic, inorganic, and natural sources, revolutionizing various biomedical applications, particularly in combating pathogenic biofilm formation. Biofilms, complex structures formed by microbial communities enveloped in exopolysaccharide matrices, pose formidable challenges to traditional antibiotics due to their high tolerance and resistance, exacerbating inefficacy issues in antibiotic treatments. QDs offer a promising solution, employing physical mechanisms like photothermal or photodynamic therapy to disrupt biofilms. Their efficacy is noteworthy, with lower susceptibility to resistance development and broad-spectrum action as compared to conventional antibiotic methods. The stability and durability of QDs ensure sustained biofilm activity, even in challenging environmental conditions. This comprehensive review delves into the synthesis, properties, and applications of Carbon Quantum Dots (CQDs), most widely used QDs, showcasing groundbreaking developments that position these nanomaterials at the forefront of cutting-edge research and innovation. These nanomaterials exhibit multifaceted mechanisms, disrupting cell walls and membranes, generating reactive oxygen species (ROS), and binding to nucleic materials, effectively inhibiting microbial proliferation. This opens transformative possibilities for healthcare interventions by providing insights into biofilm dynamics. However, challenges in size control necessitate ongoing research to refine fabrication techniques, ensure defect-free surfaces, and optimize biological activity. QDs emerge as microscopic yet potent tools, promising to contribute to a brighter future where quantum wonders shape innovative solutions to persistently challenging issues posed by pathogenic biofilms. Henceforth, this review aims to explore QDs as potential agents for inhibiting pathogenic microbial biofilms, elucidating the underlying mechanisms, addressing the current challenges, and highlighting their promising future potential.


Assuntos
Nanoestruturas , Pontos Quânticos , Pontos Quânticos/química , Antibacterianos/farmacologia , Antibacterianos/química , Biofilmes , Carbono
5.
Biomarkers ; 29(1): 7-17, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38252065

RESUMO

CONTEXT: Gynecological disorders represent a complex set of malignancies that result from a diverse array of molecular changes affecting the lives of over a million women worldwide. Ovarian, Endometrial, and Cervical cancers, Endometriosis, PCOS are the most prevalent ones that pose a grave threat to women's health. Proteomics has emerged as an invaluable tool for developing novel biomarkers, screening methods, and targeted therapeutic agents for gynecological disorders. Some of these biomarkers have been approved by the FDA, but regrettably, they have a constrained diagnostic accuracy in early-stage diagnosis as all of these biomarkers lack sensitivity and specificity. Lately, high-throughput proteomics technologies have made significant strides, allowing for identification of potential biomarkers with improved sensitivity and specificity. However, limited successes have been shown with translation of these discoveries into clinical practice. OBJECTIVE: This review aims to provide a comprehensive overview of the current and potential protein biomarkers for gynecological cancers, endometriosis and PCOS, discusses recent advances and challenges, and highlights future directions for the field. CONCLUSION: We propose that proteomics holds great promise as a powerful tool to revolutionize the fight against female reproductive diseases and can ultimately improve personalized patient outcomes in women's biomedicine.


Assuntos
Endometriose , Doenças dos Genitais Femininos , Ginecologia , Síndrome do Ovário Policístico , Neoplasias do Colo do Útero , Feminino , Humanos , Endometriose/diagnóstico , Síndrome do Ovário Policístico/diagnóstico , Proteômica , Medicina de Precisão , Biomarcadores/metabolismo , Doenças dos Genitais Femininos/diagnóstico , Doenças dos Genitais Femininos/metabolismo , Poder Psicológico
6.
Asia Pac J Clin Oncol ; 20(1): 25-31, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36722413

RESUMO

AIM: Lung cancer is the leading cause of cancer-related deaths in Australia with poor long-term survival outcomes. Stage III non-small cell lung cancer (NSCLC) is a highly heterogenous group with diverse tumor characteristics and multiple, possible treatment options. We present retrospective data on patient characteristics, treatment patterns, and long-term outcomes in stage III NSCLC patients treated at a single cancer center in New South Wales, Australia. METHODS: Stage III NSCLC patients were identified from the 'Nepean Cancer Research Biobank'. Patient demographics, cancer-related information, and long-term follow-up data were collected and analyzed. RESULTS: A total of 88 patients were eligible for analysis with 61% of them diagnosed as stage IIIA, 35% IIIB, and 4% IIIC. Induction chemotherapy was administered in 20% of the patients. Overall, 48% of the study population underwent surgery, and 38% underwent concurrent chemoradiotherapy (CCRT). Both median progression-free survival and overall survival (OS) were superior in stage IIIA patients in comparison to stage IIIB (and IIIC) patients (22 vs. 11 months, p = .018; and 58 vs. 19 months, p = .048, respectively). Patients who were younger (<65 years old), good Eastern Cooperative Oncology Group performance status (ECOG PS <2), and females had better prognosis on univariate analysis. There was a nonstatistically significant trend toward better median OS with CCRT in comparison to surgery (58 vs. 37 months, p = .87). CONCLUSIONS: Long-term outcomes remain poor, and hence better treatment strategies are urgently needed in stage III NSCLC. Equally, more robust, prospective studies would help delineate the optimal treatment modality in these patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Feminino , Humanos , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Estudos Prospectivos , Estadiamento de Neoplasias , Quimiorradioterapia
7.
PLoS One ; 18(12): e0289989, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38060499

RESUMO

The present study aims to investigate the antigenic cross reactivity between the receptor from Proteus mirabilis and spermatozoa against a common sperm immobilization factor, SIF, by calorimetric and competitive inhibition studies, and the immunogenicity of this receptor to evoke the formation of antisperm antibodies and their subsequent role in fertility outcome. The sperm binding receptor from Proteus mirabilis (PM-SBR) was extracted from ultrasonicated cell debris by treating it for 12 h at 37°C with 1 M NaCl. After being purified by gel permeation chromatography, its molecular weight as determined by SDS-PAGE was observed to be ≈ 47 kDa. The detrimental impacts of Sperm immobilizing factor (SIF) on spermatozoa viz. motility, viability, and morphology were mitigated when SIF was preincubated with various concentrations of PM-SBR. Using isothermal titration calorimetry, the entropy of the SIF-PM-SBR interaction was found to be -18.31 kJ/mol, whereas the free energy was 28.4 J/mol K. FTIR analysis was used to evaluate the binding interactions between PM-SBR and SIF. In addition, mice that were administered antibodies against PM-SBR were unable to conceive, in contrast to mice that were administered Phosphate buffer saline (PBS) or pre-immunization serum as controls. In light of this, we may conclude that anti-PM-SBR antibodies act as anti-sperm antibodies. Our work found that molecular mimicry between Proteus mirabilis and spermatozoa may cause antisperm immune reactivity. As a result of an immunological response to PM-SBR, infected individuals may produce antibodies against an epitope similar to one found on spermatozoa which helps in developing new strategies for managing autoimmune responses and infertility.


Assuntos
Infertilidade , Proteus mirabilis , Masculino , Animais , Camundongos , Sêmen/química , Espermatozoides/fisiologia , Motilidade dos Espermatozoides , Anticorpos
8.
Int J Biol Macromol ; 253(Pt 7): 127413, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37858657

RESUMO

In this work, we looked at using nickel oxide (NiO) nanocomposites with chitosan encapsulation as a nano-primer to improve wheat crop output. A straightforward green precipitation procedure was used to create the nanocomposites, and they were then characterized using several methods. According to the findings, the chitosan-encapsulated NiO nanocomposites possessed a large surface area and were resilient to changes in pH. Following this, wheat seeds were primed with the nanocomposites, and under greenhouse circumstances, the impact on crop growth was assessed. The findings demonstrated that, in comparison to the control group, nanocomposites priming considerably enhanced wheat growth and germination rate up to 99 %. In comparison to untreated plants, the wheat plants treated with the nanocomposites primer had greater plant height i.e. shoot length (11.4 cm) and root length (10.3 cm), leaf area, and biomass accumulation. Further research into the mechanism underlying the priming effect of nanocomposites on wheat growth revealed that the nanocomposites enhanced nutrient absorption, photosynthesis, and stress tolerance in wheat plants. In conclusion, our research shows that chitosan-encapsulated NiO nanocomposites have the potential to improve wheat crop productivity in an environmentally benign and long-term manner, offering a viable strategy for sustainable farming.


Assuntos
Quitosana , Nanocompostos , Triticum , Produção Agrícola/métodos , Sementes
9.
Artigo em Inglês | MEDLINE | ID: mdl-36973621

RESUMO

Removal of water pollutants (methylene blue dye and heavy metals) was achieved by zinc/manganese-doped nickel ferrites (Ni1 - xMxFe2O4, where x = 0.00, 0.025, 0.10). Degradation of dye was achieved under natural solar light illumination. Degradation studies of dye were conducted under different parameters such as contact time-80 min, dye's concentration-5 mg/L, pH-7, and dosage of ferrites-15 mg. The adsorption of dye was studied using non-linear kinetics models (pseudo-first-order and pseudo-second-order) and isotherm models (Langmuir and Freundlich). The adsorption of dye followed pseudo-first-order kinetics (R2 = 0.99377) than second-order kinetics (R2 = 0.98063) and Langmuir isotherm model (R2 = 0.96095) than Freundlich model (R2 = 0.95962) with maximum adsorption efficiency of 29.62 mg/g. Doping of nickel ferrites caused an increase in the removal percentage of methylene blue dye (80 to 90%) and inorganic effluents (75 to 95% for lead and 47 to 82% for cadmium). In addition to this, band gap energy (2.43 to 3.26 eV) (UV-Vis spectroscopy), pore radius (65.2 to 74.8 A°), and specific surface area (16.45 to 27.95 m2/g) (BET analysis) were also increased. Generally, the results of the study revealed that synthesized nanoparticles can act as potential candidate for the removal of effluents from wastewater under optimum parameters along with recyclability, reusability, and separation under the influence of a magnetic field.

10.
Colloids Surf B Biointerfaces ; 222: 113113, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36566688

RESUMO

Owing to their tolerance to antibiotics, bacterial biofilms continue to pose a threat to mankind and are leading cause for non-healing of burn wounds. Within the biofilm matrix, antibiotics become functionally inactive due to restricted penetration and enzymatic degradation leading to rise of antimicrobial resistance. The objective of present investigation was to develop and characterize levofloxacin (LFX) loaded clove oil nanoscale emulgel (LFX-NE gel) and evaluate its in vivo therapeutic efficacy in Pseudomonas aeruginosa biofilm infected burn wound in mice. The optimized emulgel was found to possess good texture profile and showed shear thinning behavior. In vitro release study demonstrated complete drug release in 8 h and emulgel was found to be stable for 3 months at 25 °C and 40 °C. In vivo study revealed biofilm dispersal, complete wound closure, re-epithelialization and collagen deposition by LFX-NE gel in comparison to various control groups. LFX-NE gel was able to clear the infection within 7 days of treatment and promote wound healing as well. Therefore, administration of LFX-incorporated NE gel could be a beneficial treatment strategy for P. aeruginosa biofilm-infected burn wounds.


Assuntos
Queimaduras , Infecções por Pseudomonas , Infecção dos Ferimentos , Camundongos , Animais , Levofloxacino/farmacologia , Pseudomonas aeruginosa , Óleo de Cravo/farmacologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Biofilmes , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/metabolismo , Infecção dos Ferimentos/microbiologia , Queimaduras/tratamento farmacológico , Queimaduras/microbiologia , Cicatrização , Infecções por Pseudomonas/tratamento farmacológico
11.
Neurol India ; 70(4): 1575-1579, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36076661

RESUMO

Background and Objective: Oxidative stress plays an important role in atherosclerosis and ischemic stroke. Due to antioxidant properties of Paraoxonase-2, we studied the implication of Paraoxonase-2 gene polymorphism (C1053G) on expression of Paraoxonase-2 gene at mRNA level in ischemic stroke patients. Material and Methods: 40 patients of ischemic stroke and 40 age and sex-matched controls were included. Paraoxonase-2 genotypes were evaluated by Polymerase Chain Reaction and Restriction Fragment Length Polymorphism and expression of Paraoxonase-2 gene at mRNA level was determined by quantitative real time Polymerase Chain Reaction analysed as delta-CT (△CT). Result and Discussion: The observed allele frequencies in patients for C and G allele were 0.61 and 0.39 respectively, and were 0.72 and 0.28 in control group. No significant association was found in C allele of C1053G polymorphism and ischemic stroke. The average △ CT value is significantly (p = 0.0001) higher in patients group (7.68 ± 2.0) as compared to controls (5.70 ± 1.8). We found a significant difference in the average delta-CT value (p = 0.0001), wherein down-regulated paraoxonase-2 gene expression (approximately 0.25 fold) was observed in case of patients as compared to controls. Down-regulated expression of paraoxonase-2 gene was observed in patients with GG genotype as compared to CG and CC genotypes in patients with ischemic stroke (p = 0.0001). Conclusion: Down-regulated Paraoxonase-2 gene expression, as evidenced by low mRNA levels in GG genotype may be one of the contributory factors in the progression of ischemic stroke.


Assuntos
Arildialquilfosfatase , Isquemia Encefálica , AVC Isquêmico , Arildialquilfosfatase/genética , Arildialquilfosfatase/metabolismo , Isquemia Encefálica/genética , Estudos de Casos e Controles , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , AVC Isquêmico/genética , Projetos Piloto , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único/genética , RNA Mensageiro/genética , Acidente Vascular Cerebral/genética
12.
J Family Med Prim Care ; 11(5): 1702-1709, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35800564

RESUMO

Background: Depression is a hidden pandemic among adolescents with multi-factorial causal risk and risk correlates. Objectives: To find the prevalence of depression and risk factors among school-going adolescents. Methods: A cross-sectional study was conducted among 838 adolescents enrolled in 6th-11th standards (age: 11-19 years) in 15 urban schools in Patna city by using the modified Patient Health Questionnaire-9 (PHQ-9); binary logistic regression was applied to find significant risk correlates. Results: Depression was noted among 51.2% adolescents of our study participants: mild 32.3%, moderate 14.3%, moderately severe 3.9%, severe depression 0.6%; among early adolescents (46.2%; boys-21.2%, girls-78.8%) and among late adolescents (55.3%, boys-34.7%, girls-65.3%). Adolescent depression was significantly associated in our study with female gender, late adolescence, higher classes (9th-11th), vegetarian diet, soft drink consumption, fast foods, screen time, domestic harassment, academic dissatisfaction, parental discord as well as mental illness. Girls had higher risk who were in higher classes, on a vegetarian diet, habitually on soft drink, more screen time (>3 h), face more family nuisance, parents brawling frequently, and suffering from known mental diseases. Conclusion: Depression was noted in more than half of the adolescents, with a higher prevalence in girls, scholastic failure, higher grades, vegetarian diet, more screen time, familial disease, and conflict.

13.
Microb Pathog ; 168: 105587, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35588965

RESUMO

Cervical cancer is the fourth most common cause of mortality worldwide. Persistent infection with high-risk human papillomaviruses (hrHPV) is a known significant risk factor in cervical neoplasia development (CN). Though HPV contributes to carcinogenesis, other factors provide an ideal niche for persistence of HPV, especially, coinfection with Chlamydia trachomatis (CT) which has been linked to CN development. CT infection is associated with inflammation, cell proliferation, EMT transition and anti-apoptotic processes. To better understand the correlation between HPV-CT coinfection and CN development, a literature review was conducted on the prevalence of HPV-CT coinfection focusing on the role of infection-induced inflammation as HPV-CT coinfection creates an environment for cellular transformation, activates an innate immune response and triggers EMT transition. Moreover, inflammation plays a crucial role in developing neoplasia as there is a decrease in effector cells and a change in the levels of players like ROS and miRs. CT infection induces chronic inflammation followed by cervical epithelial cell damage and increases susceptibility to HPV infection which may lead to cellular transformation. The literature search was performed based on a comprehensive investigation of publications in the PubMed journal database and Scopus, on the development of CN. We have reviewed the prevalence of HPV-CT infection and the factors increasing the risk of developing CN.


Assuntos
Infecções por Chlamydia , Coinfecção , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Infecções por Chlamydia/complicações , Infecções por Chlamydia/epidemiologia , Chlamydia trachomatis , Coinfecção/epidemiologia , Feminino , Humanos , Inflamação , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia
14.
Clin Breast Cancer ; 22(3): 200-211, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34625387

RESUMO

The microbiome assisted tumor microenvironment (TME) supports the tumors by modulating multiple mechanisms. Recent studies reported that microbiome dysbiosis is the main culprit of immune suppressive phenotypes of TME. Further, it has been documented that immune suppressive stimulate metastatic phenotype in TME via modulating signaling pathways, cell differentiation, and innate immune response. This review aims at providing comprehensive developments in microbiome and breast TME interface. The combination of microbiome and breast cancer, breast TME and microbiome or microbial dysbiosis, microbiome and risk of breast cancer, microbiome and phytochemicals or anticancer drugs were as used keywords to retrieve literature from PubMed, Google scholar, Scopus, Web of Science from 2015 onwards. Based on the literature, we presented the impact of TME assisted microbiome dysbiosis and estrobolome in breast cancer risk, drug resistance, and antitumor immunity. We have discussed the influence of antibiotics on the breast microbiome. we also presented the possible dietary phytochemicals that target microbiome dysbiosis to restore the tumor suppression immune environment in breast TME. We presented the microbiome as a possible marker for breast cancer diagnosis. This study will help in the identification of microbiome as a novel target and diagnostic markers and phytochemicals and microbiome metabolites for breast cancer treatment.


Assuntos
Neoplasias da Mama , Microbiota , Mama , Neoplasias da Mama/tratamento farmacológico , Disbiose , Feminino , Humanos , Microambiente Tumoral
15.
J Phys Condens Matter ; 33(27)2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-33957615

RESUMO

The double perovskite compound Tb2CoMnO6has been investigated using x-ray absorption spectroscopy (XAS), Raman spectroscopy, magnetic measurements andab initioband structure calculations. It is observed that both anti-ferromagnetic (AFM) and ferromagnetic (FM) phase coexist in this material. The presence of anti-site disorder (ASD) has been established from the analysis of neutron diffraction data. Moreover, a prominent metamagnetic transition is observed in theM(H) behavior that has been explained with the drastic reorientation of the pinned domain which are aligned antiparallel by the antiphase boundaries (APBs) at zero field. The ASD further gives rise to spin frustration at low temperature which leads to the re-entrant cluster glass ∼33 K. The coupling between phononic degree of freedom and spin in the system has also been demonstrated. It is observed that the theoretical calculation is consistent with that of the experimentally observed behavior.

16.
Microb Pathog ; 152: 104780, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33545325

RESUMO

Cellular transformation to malignancy is a multifactorial process strongly linked with microbiome dysbiosis. The female reproductive tract (FRT) is inhabited by specific Lactobacillus spp which play a significant role in maintaining a homeostatic balance and providing resistance to perturbation. Any imbalance in the resident microbiota of the FRT results in cervicovaginal dysbiosis and increased predisposition to viral and bacterial infections. In the present review, we discuss the critical role played by the cervicovaginal microbiome in maintaining cervicovaginal homeostasis. Loss of the mutualistic relationship between cervicovaginal microbiota and the host leads to increased susceptibility to Human papilloma virus (HPV) infection. HPV in coinfection with Chlamydia trachomatis has been linked with increased risk for cellular transformation. The progression to cervical neoplasia is a multistep process regulated by cellular and epigenetic changes mediated by oncogenes and miRNA. Exosomes derived from the infected cells play an important role in the pathological development and progression to cervical neoplasia as they harbor the regulatory molecules like miRNA, proteins and prooncogenic factors which may facilitate cellular transformation.


Assuntos
Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Chlamydia trachomatis , Disbiose , Feminino , Humanos , Papillomaviridae/genética , Infecções por Papillomavirus/complicações
17.
Comb Chem High Throughput Screen ; 24(9): 1514-1526, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33155890

RESUMO

INTRODUCTION: Enzymatic degradation of peptidoglycan, a structural cell wall component of Gram-positive bacteria, has attracted considerable attention being a specific target for many known antibiotics. METHODS: Peptidoglycan hydrolases are involved in bacterial lysis through peptidoglycan degradation. ß-N-acetyl-glucosaminidase, a peptidoglycan hydrolase, acts on O-glycosidic bonds formed by N-acetylglucosamine and N-acetyl muramic acid residues of peptidoglycan. Aim of present study was to study the action of ß-N-acetylglucosaminidase, on methicillin-resistant Staphylococcus aureus (MRSA) and other Gram-negative bacteria. RESULTS: We investigated its dynamic behaviour using molecular dynamics simulation and observed that serine and alanine residues are involved in catalytic reaction in addition to aspartic acid, histidine, lysine and arginine residues. When simulated in its bound state, the RMSD values were found lesser than crystal form in the time stamp of 1000 picoseconds revealing its stability. Structure remained stably folded over 1000 picoseconds without undergoing any major change further confirming the stability of complex. CONCLUSION: It can be concluded that enzymes belonging to this category can serve as a tool in eradicating Gram-positive pathogens and associated infections.


Assuntos
Acetilglucosaminidase/metabolismo , Peptidoglicano/metabolismo , Serratia marcescens/enzimologia , Acetilglucosaminidase/isolamento & purificação , Configuração de Carboidratos , Humanos , Modelos Moleculares , Peptidoglicano/química
18.
Semin Cancer Biol ; 69: 376-390, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-31301361

RESUMO

Female-specific cancers are the most common cancers in women worldwide. Early detection methods remain unavailable for most of these cancers, signifying that most of them are diagnosed at later stages. Furthermore, current treatment options for most female-specific cancers are surgery, radiation and chemotherapy. Although important milestones in molecularly targeted approaches have been achieved lately, current therapeutic strategies for female-specific cancers remain limited, ineffective and plagued by the emergence of chemoresistance, which aggravates prognosis. Recently, the application of nanotechnology to the medical field has allowed the development of novel nano-based approaches for the management and treatment of cancers, including female-specific cancers. These approaches promise to improve patient survival rates by reducing side effects, enabling selective delivery of drugs to tumor tissues and enhancing the uptake of therapeutic compounds, thus increasing anti-tumor activity. In this review, we focus on the application of nano-based technologies to the design of novel and innovative diagnostic and therapeutic strategies in the context of female-specific cancers, highlighting their potential uses and limitations.


Assuntos
Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos , Neoplasias dos Genitais Femininos/tratamento farmacológico , Nanomedicina , Nanopartículas/administração & dosagem , Animais , Feminino , Neoplasias dos Genitais Femininos/patologia , Humanos , Nanopartículas/química
19.
Cancer Rep (Hoboken) ; 3(3): e1246, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32671983

RESUMO

BACKGROUND: Nivolumab is an anti-PD1 immune checkpoint inhibitor commonly used for the treatment of solid organ and hematological malignancies. Severe infusion reaction due to nivolumab is quite rare. CASE: We report a case of severe infusion reaction due to nivolumab necessitating ICU admission and withdrawal of further nivolumab use in a patient with metastatic non-small cell lung cancer. CONCLUSION: Our knowledge and expertise with the use of immune checkpoint inhibitors are still evolving. This report highlights one of the rare possible side-effects that clinicians and patients may have to face with increasing indications and use of nivolumab in day to day practice.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Infusões Intravenosas/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Nivolumabe/efeitos adversos , Antineoplásicos Imunológicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Nivolumabe/administração & dosagem , Prognóstico
20.
Crit Rev Oncol Hematol ; 151: 102968, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32416345

RESUMO

Hepatocellular carcinoma (HCC) is the fifth most prevalent malignancy worldwide. Despite advances in imaging techniques, early diagnosis and management remain very poor. The early diagnosis of HCC requires diagnostic and imaging technologies with high sensitivity and precise quantification ability and with no tissue penetration limit. Nanotechnology-based cancer imaging is a rapidly emerging research area with significant applications in the diagnosis and treatment of cancer, which we review here with application to HCC. Furthermore, we discuss the combination of functional nanotheranostics and magnetic resonance imaging (MRI) for targeted delivery of phytochemical therapeutics, chemotherapeutic drugs, RNAi-based therapeutics, and vaccinations. Finally, this review presents the importance of MRI biomarkers for monitoring HCC treatment response. The use of advanced nanotheranostics as MRI contrast agents for imaging, diagnosis and drug delivery may enhance HCC management and provide a new area of research in tumor imaging technology.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Polímeros/química , Antineoplásicos/administração & dosagem , Portadores de Fármacos , Humanos , Imageamento por Ressonância Magnética , Nanotecnologia
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