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1.
Nature ; 626(7998): 401-410, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38297129

RESUMO

Ferroptosis is a form of cell death that has received considerable attention not only as a means to eradicate defined tumour entities but also because it provides unforeseen insights into the metabolic adaptation that tumours exploit to counteract phospholipid oxidation1,2. Here, we identify proferroptotic activity of 7-dehydrocholesterol reductase (DHCR7) and an unexpected prosurvival function of its substrate, 7-dehydrocholesterol (7-DHC). Although previous studies suggested that high concentrations of 7-DHC are cytotoxic to developing neurons by favouring lipid peroxidation3, we now show that 7-DHC accumulation confers a robust prosurvival function in cancer cells. Because of its far superior reactivity towards peroxyl radicals, 7-DHC effectively shields (phospho)lipids from autoxidation and subsequent fragmentation. We provide validation in neuroblastoma and Burkitt's lymphoma xenografts where we demonstrate that the accumulation of 7-DHC is capable of inducing a shift towards a ferroptosis-resistant state in these tumours ultimately resulting in a more aggressive phenotype. Conclusively, our findings provide compelling evidence of a yet-unrecognized antiferroptotic activity of 7-DHC as a cell-intrinsic mechanism that could be exploited by cancer cells to escape ferroptosis.


Assuntos
Linfoma de Burkitt , Desidrocolesteróis , Ferroptose , Neuroblastoma , Animais , Humanos , Linfoma de Burkitt/metabolismo , Linfoma de Burkitt/patologia , Sobrevivência Celular , Desidrocolesteróis/metabolismo , Peroxidação de Lipídeos , Transplante de Neoplasias , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Oxirredução , Fenótipo , Reprodutibilidade dos Testes
2.
Crit Rev Microbiol ; : 1-40, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38425122

RESUMO

Antibiotics have remained the cornerstone for the treatment of bacterial infections ever since their discovery in the twentieth century. The uproar over antibiotic resistance among bacteria arising from genome plasticity and biofilm development has rendered current antibiotic therapies ineffective, urging the development of innovative therapeutic approaches. The development of antibiotic resistance among bacteria has further heightened the clinical failure of antibiotic therapy, which is often linked to its low bioavailability, side effects, and poor penetration and accumulation at the site of infection. In this review, we highlight the potential use of siderophores, antibodies, cell-penetrating peptides, antimicrobial peptides, bacteriophages, and nanoparticles to smuggle antibiotics across impermeable biological membranes to achieve therapeutically relevant concentrations of antibiotics and combat antimicrobial resistance (AMR). We will discuss the general mechanisms via which each delivery system functions and how it can be tailored to deliver antibiotics against the paradigm of mechanisms underlying antibiotic resistance.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38497194

RESUMO

Transbronchial lung cryobiopsy (TBLC) with flexible bronchoscope represents an encouraging modality to obtain a larger size specimen without crush artifact, and a higher diagnostic yield in patients with diffuse parenchymal lung lesions/diseases as compared to conventional transbronchial lung biopsy, and fewer complications as opposed to surgical lung biopsy. Artificial airway is preferred as it provides better airway protection in cases of severe bleeding. Although various researchers have published data on different modalities, the data is not sufficient to standardize a single technique. This study describes the procedural technique, safety, and yield of TBLC using a flexible bronchoscope with an endobronchial blocker. We performed a retrospective analysis of 100 consecutive patients who underwent TBLC using flexible bronchoscopy from May 2018 to June 2022. TBLC samples were obtained under moderate sedation without the use of artificial airway or fluoroscopy. Among the 100 patients, the majority were male (63%). The mean age of the enrolled patients was 44.43±15.92 years. The predominant diagnoses in our study were hypersensitivity pneumonitis (27%), followed by sarcoidosis (12%) and tuberculosis (10%). We obtained alveolated lung tissue in 90 out of 100 cases with a median biopsy size of 5 mm (in greatest dimension, interquartile range 5-4 mm), resulting in a specific histopathological diagnosis in 82 cases. The most frequent complications were bleeding and pneumothorax (13%). Mild bleeding occurred in 58% of the patients, and moderate bleeding occurred in 20% of the patients. There was no episode of severe/life-threatening bleeding. None of the patients required intensive care unit admission or endotracheal intubation. In conclusion, the use of TBLC through flexible bronchoscopy with an endobronchial blocker emerges as a minimally invasive, secure, time-efficient, and readily reproducible technique. Significantly, this procedure can be seamlessly executed in the bronchoscopy suite, eliminating the requirement for an artificial airway or general anesthesia.

4.
Chem Biodivers ; 20(3): e202201191, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36811279

RESUMO

The effectiveness of treating bacterial infections is seriously threatened by the emergence of bacterial resistance to chemical treatment. Growth of microbes in biofilm is one of the main causes of resistance to antimicrobial drugs. Quorum sensing (QS) inhibition, which targets the QS signalling system by obstructing cell-cell communication, was developed as an alternative treatment by creating innovative anti-biofilm drugs. Therefore, the goal of this study is to develop novel antimicrobial drugs that are effective against Pseudomonas aeruginosa by inhibiting QS and acting as anti-biofilm agents. In this study, N-(2- and 3-pyridinyl)benzamide derivatives were selected to design and syntheses. Antibiofilm activity was revealed by all the synthesized compounds and the biofilm was visibly impaired, and the OD595nm readings of solubilized biofilm cells presented a momentous difference between the treated and untreated biofilms. The best anti-QS zone was observed for compound 5d and found to be 4.96 mm. Through in silico research, the physicochemical characteristics and binding manner of these produced compounds were examined. For the purpose of understanding the stability of the protein and ligand complex, molecular dynamic simulation was also carried out. The overall findings showed that N-(2- and 3-pyridinyl)benzamide derivatives could be the key to creating effective newer anti-quorum sensing drugs that are effective against different bacteria.


Assuntos
Anti-Infecciosos , Pseudomonas aeruginosa , Antibacterianos/química , Percepção de Quorum , Biofilmes , Anti-Infecciosos/farmacologia , Proteínas de Bactérias/metabolismo
5.
Chem Biodivers ; 20(9): e202300647, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37602712

RESUMO

The development of bacterial resistance to chemical therapy poses a severe danger to efficacy of treating bacterial infections. One of the key factors for resistance to antimicrobial medications is growth of bacteria in biofilm. Quorum sensing (QS) inhibition was created as an alternative treatment by developing novel anti-biofilm medicines. Cell-cell communication is impeded by QS inhibition, which targets QS signaling pathway. The goal of this work is to develop newer drugs that are effective against Pseudomonas aeruginosa by decreasing QS and acting as anti-biofilm agents. In this investigation, N-(benzo[d]thiazol-2-yl)benzamide/N-(thiazol-2-yl)benzamide derivatives 3a-h were designed and synthesized in good yields. Further, molecular docking analyses revealed that binding affinity values were founded -11.2 to -7.6 kcal/mol that were moderate to good. The physicochemical properties of these prepared compounds were investigated through in-silico method. Molecular dynamic simulation was also used to know better understanding of stability of the protein and ligand complex. Comparing N-(benzo[d]thiazol-2-yl)benzamide 3a to salicylic acid (4.40±0.10) that was utilised as standard for quorum sensing inhibitor, the anti-QS action was found greater for N-(benzo[d]thiazol-2-yl)benzamide 3a (4.67±0.45) than salicylic acid (4.40±0.10). Overall, research results suggested that N-(benzo[d]thiazol-2-yl)benzamide/N-(thiazol-2-yl)benzamide derivatives 3a-h may hold to develop new quorum sensing inhibitors.


Assuntos
Pseudomonas aeruginosa , Percepção de Quorum , Simulação de Acoplamento Molecular , Biofilmes , Ácido Salicílico/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Proteínas de Bactérias/metabolismo
6.
J Assoc Physicians India ; 71(5): 11-12, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37355820

RESUMO

INTRODUCTION: Asthma and chronic obstructive pulmonary disease (COPD) are characterized by chronic airway inflammation. Lack of knowledge about the correct inhalation techniques leads to poor control of both diseases. This study aimed to study the effectiveness of inhalation technique training in patients with COPD and asthma. MATERIALS AND METHODS: A total of 132 patients fulfilling the inclusion criteria were trained with the correct technique of inhalation on day 0 and at the end of 1 and 6 months. Evaluation of technique training was done on these three occasions posttraining. The mean score of devices was obtained, and the mean inhalation technique score of various devices was compared. RESULTS: Out of 132 patients, 65.1% (86/132) patients were using a dry powdered inhaler (DPIs), 26.5% (35/132) patients used metered dose inhalers (MDIs), and 8.4% (11/132) patients used MDI with spacer. The mean scores of patients using MDI at baseline were 5.68 ± 0.83, and after 1 month, 6.68 ± 0.58 (p < 0.000). The inhalation technique mean score of MDI improved after 6 months, 7.02 ± 0.56 as compared to baseline (p < 0.008) mean score of the patients using DPIs improved after 1 month, 5.53 ± 0.58 as compared to baseline 4.37 ± 5.53 (p < 0.000). There was no statistical improvement in the device mean score of DPIs after 6 months, 5.62 ± 0.55 when compared with 1 month, 5.53 ± 0.58 (p < 0.117). Patients who used pressurized metered-dose inhalers (pMDI) with spacers improved their inhalation score after 1 month by 6.90 ± 0.94 as compared to the baseline score of 6.90 ± 0.94 (p < 0.001). The mean score decreased marginally after 6 months, 7.818 ± 0.60, as compared to the score at the end of 1 month of 8.27 ± 0.64 (p < 0.053). DISCUSSION: Patients showed improvement in the technique of inhalation after educational training, reinstructions, and a standard checklist.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Asma/tratamento farmacológico , Inaladores Dosimetrados , Administração por Inalação , Nebulizadores e Vaporizadores
7.
World J Microbiol Biotechnol ; 39(10): 268, 2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37528258

RESUMO

Salmonella enterica serovar Typhi is a significant cause of typhoid fever and a major public health problem. The ability of S. Typhi to form biofilms on living and non-living surfaces results in antibiotic resistance and poses a major challenge in health care. In this study, we assessed the ability of zingerone alone and in combination with antibiotics against the motility phenotypes and biofilm-forming ability of S. Typhi. Results showed that zingerone effectively reduced the swimming, swarming, and twitching phenotypes and exhibited biofilm inhibition potential. Moreover, zingerone enhanced the antibiofilm activity of ciprofloxacin and kanamycin. Microscopic analysis revealed a thinner biofilm in the presence of zingerone, which may have enhanced the antibiofilm efficacy of the antibiotics. The microscopic analysis showed that the presence of zingerone resulted in a reduction in the thickness of the biofilm, potentially increasing the antibiofilm efficacy of the antibiotics. In silico molecular docking and simulation studies further indicated that zingerone may bind to the fimbriae subunits (FimA, FimC, FimH, and FimY) of S. Typhi and form stable interactions. These findings provide important insights into the potential of zingerone to target biofilm-associated Salmonella infections. Further research is considered a promising option for designing innovative approaches to prevent infections associated with biofilms. Schematic representation of the role of zingerone in biofilm, motility inhibition and molecular interactions with biofilm associated proteins.


Assuntos
Antibacterianos , Salmonella , Antibacterianos/farmacologia , Simulação de Acoplamento Molecular , Biofilmes , Salmonella typhi
8.
Molecules ; 27(21)2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36364411

RESUMO

Microbial biodiversity includes biotic and abiotic components that support all life forms by adapting to environmental conditions. Climate change, pollution, human activity, and natural calamities affect microbial biodiversity. Microbes have diverse growth conditions, physiology, and metabolism. Bacteria use signaling systems such as quorum sensing (QS) to regulate cellular interactions via small chemical signaling molecules which also help with adaptation under undesirable survival conditions. Proteobacteria use acyl-homoserine lactone (AHL) molecules as autoinducers to sense population density and modulate gene expression. The LuxI-type enzymes synthesize AHL molecules, while the LuxR-type proteins (AHL transcriptional regulators) bind to AHLs to regulate QS-dependent gene expression. Diverse AHLs have been identified, and the diversity extends to AHL synthases and AHL receptors. This review comprehensively explains the molecular diversity of AHL signaling components of Pseudomonas aeruginosa, Chromobacterium violaceum, Agrobacterium tumefaciens, and Escherichia coli. The regulatory mechanism of AHL signaling is also highlighted in this review, which adds to the current understanding of AHL signaling in Gram-negative bacteria. We summarize molecular diversity among well-studied QS systems and recent advances in the role of QS proteins in bacterial cellular signaling pathways. This review describes AHL-dependent QS details in bacteria that can be employed to understand their features, improve environmental adaptation, and develop broad biomolecule-based biotechnological applications.


Assuntos
Acil-Butirolactonas , Percepção de Quorum , Humanos , Pseudomonas aeruginosa/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Bactérias Gram-Negativas/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo
9.
Monaldi Arch Chest Dis ; 93(3)2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-36200689

RESUMO

The risk of death in HIV-TB coinfected individuals is far greater than in HIV-only patients. It is critical to provide timely and appropriate therapy in HIV-TB coinfected patients in order to reduce morbidity and mortality. The purpose of this study was to evaluate the clinical presentation and outcome of TB treatment in HIV-TB co-infected patients receiving daily anti-tubercular therapy (ATT) and concurrent antiretroviral therapy (ART) at a tertiary respiratory care centre in New Delhi, India. The research was cross-sectional, observational, and hospital-based A. From September 2018 to August 2019, a total of 53 patients with HIV-TB coinfection were enrolled at the Institute's ART centre. Patients were evaluated with a structured proforma. Data were evaluated using SPSS version 23.0 and p-value of less than 0.05 was considered statistically significant. Among the patients enrolled, the mean age was 35.98 years. Among the patients enrolled, 56.6% patients had EPTB, 32% had PTB and 11.3% had both PTB and EPTB. The majority of the enrolled patients (n=46, 86.7%) had favourable TB treatment outcomes, while 13.3% (n=7) had unfavourable outcome [including death (n=5) and loss to follow up (n=2)]. During the study and follow-up period, no patients transferred out or relapsed. In univariate analysis, low SES, bedridden functional status, low BMI, anaemia, hypoalbuminemia, and a low CD-4 cell count (<100 cells/mm3 were significantly associated with an unfavourable outcome. Bedridden functional status (p=0.002), anaemia (p=0.040), and low BMI (p<0.001) were independently associated with a poor outcome. Adequate disease knowledge and health education can be very beneficial in reducing morbidity and mortality. Early ART in combination with ATT can reduce mortality in TB-HIV co-infected patients.


Assuntos
Coinfecção , Infecções por HIV , Tuberculose , Humanos , Adulto , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Tuberculose/complicações , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Coinfecção/tratamento farmacológico , Coinfecção/complicações , Estudos Transversais , Resultado do Tratamento
10.
Biophys J ; 119(2): 360-374, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32585130

RESUMO

An understanding of the structure-dynamics relationship is essential for understanding how a protein works. Prior research has shown that the activity of a protein correlates with intradomain dynamics occurring at picosecond to millisecond timescales. However, the correlation between interdomain dynamics and the function of a protein is poorly understood. Here, we show that communications between the catalytic and hemopexin domains of matrix metalloprotease-1 (MMP1) on type 1 collagen fibrils correlate with its activity. Using single-molecule Förster resonance energy transfer, we identified functionally relevant open conformations in which the two MMP1 domains are well separated, which were significantly absent for catalytically inactive point mutant (E219Q) of MMP1 and could be modulated by an inhibitor or an enhancer of activity. The observed relevance of open conformations resolves the debate about the roles of open and closed MMP1 structures in function. We fitted the histograms of single-molecule Förster resonance energy transfer values to a sum of two Gaussians and the autocorrelations to an exponential and power law. We used a two-state Poisson process to describe the dynamics and calculate the kinetic rates from the fit parameters. All-atom and coarse-grained simulations reproduced some of the experimental features and revealed substrate-dependent MMP1 dynamics. Our results suggest that an interdomain separation facilitates opening up the catalytic pocket so that the collagen chains come closer to the MMP1 active site. Coordination of functional conformations at different parts of MMP1 occurs via allosteric communications that can take place via interactions mediated by collagen even if the linker between the domains is absent. Modeling dynamics as a Poisson process enables connecting the picosecond timescales of molecular dynamics simulations with the millisecond timescales of single-molecule measurements. Water-soluble MMP1 interacting with water-insoluble collagen fibrils poses challenges for biochemical studies that the single-molecule tracking can overcome for other insoluble substrates. Interdomain communications are likely important for multidomain proteins.


Assuntos
Metaloproteinase 1 da Matriz , Simulação de Dinâmica Molecular , Domínio Catalítico , Cinética , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 1 da Matriz/metabolismo , Proteínas
11.
J Assoc Physicians India ; 67(8): 79-82, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31562727

RESUMO

Gross electrolytes disturbances including hypokalemia, hypomagnesaemia, and hypocalcaemia have been reported in tuberculosis patients who have been treated with capreomycin.1-3 Capreomycin is recommended in the treatment of M. tuberculosis isolates resistant to kanamycin at baseline in multi drug resistant tuberculosis patients (MDR - TB) and treatment of extensively drug resistant tuberculosis (XDR-TB) under programmatic management of drug resistant tuberculosis (PMDT) in India.4 We report a case of tetany in a extensively drug resistant tuberculosis (XDR-TB) patient treated with capreomycin. She developed hypokalemia after 7 weeks of administration of injection capreomycin intramuscularly daily in dose of 750 mg. Hypokalemia was refractory to intravenous potassium replacement therapy. At 12 weeks during the treatment she developed tetany and hypocalcaemia. Hypomagnesaemia was also associated with hypocalcaemia and hypokalemia. Normal level of serum potassium and calcium were achieved with correction of hypomagnesaemia.


Assuntos
Antibióticos Antituberculose/uso terapêutico , Capreomicina/uso terapêutico , Tuberculose Extensivamente Resistente a Medicamentos , Mycobacterium tuberculosis , Tetania/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos , Antituberculosos , Feminino , Humanos , Índia , Testes de Sensibilidade Microbiana
12.
Protein Expr Purif ; 148: 59-67, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29626520

RESUMO

MMP1 is an essential enzyme for tissue remodeling both in normal and pathological states. We report a method of purifying activated human MMP1 in E. coli without using urea or 4-Aminophenylmercuric acetate (APMA). Instead, a non-ionic detergent, Triton X-100, was used in the lysis buffer to solubilize MMP1 followed by the protease activities of both trypsin and MMP1 to digest E. coli proteins and activate pro-MMP1. Identity of activated MMP1 was confirmed by Western blot using anti-human MMP1 antibodies, whereas the mass was determined to be 43 kD using matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI TOF-MS). Collagen and gelatin degradation by purified MMP1 were confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE) of degraded FITC-labeled type-1 collagen and gelatin zymogram. Broad-spectrum protease activity of purified MMP1 was also confirmed by lysis of native E. coli proteins. Inexpensive high throughput purification of recombinant human MMP1 in E. coli will enable easier MMP1 production for diverse applications.


Assuntos
Metaloproteinase 1 da Matriz/química , Metaloproteinase 1 da Matriz/isolamento & purificação , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Colágeno/química , Eletroforese em Gel de Poliacrilamida , Escherichia coli/genética , Gelatina/química , Humanos , Metaloproteinase 1 da Matriz/genética , Proteólise , Proteínas Recombinantes/genética , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
14.
J Basic Microbiol ; 55(5): 566-78, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25283438

RESUMO

Pathogenicity of opportunistic Pseudomonas aeruginosa is mediated through expression of different virulence determinants, most of which are under the control of quorum sensing. Besides acylhomoserine lactones, P. aeruginosa produces Pseudomonas quinolone signal (PQS) molecules which co-regulate expression of overlapping subset of genes. In the present study, effect of mutations in the pqs genes on the production of virulence factors, biofilm, and membrane vesicles (MVs) was studied using standard strain and isogenic pqs mutants of P. aeruginosa. Mutations in pqs genes severely reduced elastase, pyocyanin, siderophores, biofilm formation, and production of MVs. Further, effect of synthetic PQS on virulence of P. aeruginosa and its correlation with MVs was investigated. Supplementation of PQS resulted in enhancement of phenotypic expression of virulence factors and biofilm forming capacity of these strains. Restoration of virulent phenotype of mutants in presence of PQS indicated that PQS system play an important role in the virulence of P. aeruginosa. In addition, PQS also induced substantial release of MVs in all strains. When vesicles containing natural PQS were added to the mutants, significant increase in production of virulence factors was observed. This augmentation of the virulence traits may be associated with the efficient delivery of PQS among bacterial cells, which could be one possible mechanism of pqs system contributing to the overall virulence of P. aeruginosa.


Assuntos
Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Quinolonas/metabolismo , Transdução de Sinais , Fatores de Virulência/metabolismo , Biofilmes/crescimento & desenvolvimento , Vias Biossintéticas/genética , Vesículas Extracelulares/metabolismo , Mutação , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo , Virulência
15.
Environ Sci Pollut Res Int ; 31(15): 22199-22242, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38411907

RESUMO

Bacteriophages infect and replicate within bacteria and play a key role in the environment, particularly in microbial ecosystems and bacterial population dynamics. The increasing recognition of their significance stems from their wide array of environmental and biotechnological uses, which encompass the mounting issue of antimicrobial resistance (AMR). Beyond their therapeutic potential in combating antibiotic-resistant infections, bacteriophages also find vast applications such as water quality monitoring, bioremediation, and nutrient cycling within environmental sciences. Researchers are actively involved in isolating and characterizing bacteriophages from different natural sources to explore their applications. Gaining insights into key aspects such as the life cycle of bacteriophages, their host range, immune interactions, and physical stability is vital to enhance their application potential. The establishment of diverse phage libraries has become indispensable to facilitate their wide-ranging uses. Consequently, numerous protocols, ranging from traditional to cutting-edge techniques, have been developed for the isolation, detection, purification, and characterization of bacteriophages from diverse environmental sources. This review offers an exploration of tools, delves into the methods of isolation, characterization, and the extensive environmental applications of bacteriophages, particularly in areas like water quality assessment, the food sector, therapeutic interventions, and the phage therapy in various infections and diseases.


Assuntos
Bacteriófagos , Terapia por Fagos , Ecossistema , Bactérias , Biotecnologia , Terapia por Fagos/métodos , Antibacterianos
16.
PeerJ ; 12: e16804, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38313028

RESUMO

Once thought to be a unique capability of the Langerhans islets in the pancreas of mammals, insulin (INS) signaling is now recognized as an evolutionarily ancient function going back to prokaryotes. INS is ubiquitously present not only in humans but also in unicellular eukaryotes, fungi, worms, and Drosophila. Remote homologue identification also supports the presence of INS and INS receptor in corals where the availability of glucose is largely dependent on the photosynthetic activity of the symbiotic algae. The cnidarian animal host of corals operates together with a 20,000-sized microbiome, in direct analogy to the human gut microbiome. In humans, aberrant INS signaling is the hallmark of metabolic disease, and is thought to play a major role in aging, and age-related diseases, such as Alzheimer's disease. We here would like to argue that a broader view of INS beyond its human homeostasis function may help us understand other organisms, and in turn, studying those non-model organisms may enable a novel view of the human INS signaling system. To this end, we here review INS signaling from a new angle, by drawing analogies between humans and corals at the molecular level.


Assuntos
Antozoários , Ilhotas Pancreáticas , Animais , Humanos , Antozoários/metabolismo , Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Pâncreas/metabolismo , Transdução de Sinais
17.
Biomedicines ; 11(3)2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-36979744

RESUMO

Sepsis is a life-threatening condition characterized by an uncontrolled inflammatory response to an infectious agent and its antigens. Immune cell activation against the antigens causes severe distress that mediates a strong inflammatory response in vital organs. Sepsis is responsible for a high rate of morbidity and mortality in immunosuppressed patients. Monoclonal antibody (mAb)-based therapeutic strategies are now being explored as a viable therapy option for severe sepsis and septic shock. Monoclonal antibodies may provide benefits through two major strategies: (a) monoclonal antibodies targeting the pathogen and its components, and (b) mAbs targeting inflammatory signaling may directly suppress the production of inflammatory mediators. The major focus of mAb therapies has been bacterial endotoxin (lipopolysaccharide), although other surface antigens are also being investigated for mAb therapy. Several promising candidates for mAbs are undergoing clinical trials at present. Despite several failures and the investigation of novel targets, mAb therapy provides a glimmer of hope for the treatment of severe bacterial sepsis and septic shock. In this review, mAb candidates, their efficacy against controlling infection, with special emphasis on potential roadblocks, and prospects are discussed.

18.
Biomedicines ; 11(6)2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37371705

RESUMO

Cancer is a significant challenge for effective treatment due to its complex mechanism, different progressing stages, and lack of adequate procedures for screening and identification. Pancreatic cancer is typically identified in its advanced progression phase with a low survival of ~5 years. Among cancers, pancreatic cancer is also considered a high mortality-causing casualty over other accidental or disease-based mortality, and it is ranked seventh among all mortality-associated cancers globally. Henceforth, developing diagnostic procedures for its early detection, understanding pancreatic cancer-linked mechanisms, and various therapeutic strategies are crucial. This review describes the recent development in pancreatic cancer progression, mechanisms, and therapeutic approaches, including molecular techniques and biomedicines for effectively treating cancer.

19.
ACS Omega ; 8(24): 21391-21409, 2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-37360468

RESUMO

Biofilm-associated infections have emerged as a significant public health challenge due to their persistent nature and increased resistance to conventional treatment methods. The indiscriminate usage of antibiotics has made us susceptible to a range of multidrug-resistant pathogens. These pathogens show reduced susceptibility to antibiotics and increased intracellular survival. However, current methods for treating biofilms, such as smart materials and targeted drug delivery systems, have not been found effective in preventing biofilm formation. To address this challenge, nanotechnology has provided innovative solutions for preventing and treating biofilm formation by clinically relevant pathogens. Recent advances in nanotechnological strategies, including metallic nanoparticles, functionalized metallic nanoparticles, dendrimers, polymeric nanoparticles, cyclodextrin-based delivery, solid lipid nanoparticles, polymer drug conjugates, and liposomes, may provide valuable technological solutions against infectious diseases. Therefore, it is imperative to conduct a comprehensive review to summarize the recent advancements and limitations of advanced nanotechnologies. The present Review encompasses a summary of infectious agents, the mechanisms that lead to biofilm formation, and the impact of pathogens on human health. In a nutshell, this Review offers a comprehensive survey of the advanced nanotechnological solutions for managing infections. A detailed presentation has been made as to how these strategies may improve biofilm control and prevent infections. The key objective of this Review is to summarize the mechanisms, applications, and prospects of advanced nanotechnologies to provide a better understanding of their impact on biofilm formation by clinically relevant pathogens.

20.
Naunyn Schmiedebergs Arch Pharmacol ; 396(4): 633-647, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36585999

RESUMO

The rhizomes of ginger have been in use in many forms of traditional and alternative medicines. Besides being employed as condiment and flavoring agent, it is used in the treatment of nausea, osteoarthritis, muscle pain, menstrual pain, chronic indigestion, Alzheimer's disease, and cancer. Ginger rhizome contains volatile oils, phenolic compounds and resins, and characterization studies showed that [6]-gingerol, [6]-shogaol, and [6]-paradol are reported to be the pharmacologically active components. Gingerol is a major chemical constituent found as volatile oil in the rhizomes of ginger. It has several medicinal benefits and used for the treatment of rheumatoid arthritis, nausea, cancer, and diabetes. Many studies have been carried out in various parts of the world to isolate and standardize gingerol for their use as a complementary medicine. The present review summarizes wide range of research studies on gingerol and its pharmacological roles in various metabolic diseases.


Assuntos
Catecóis , Zingiber officinale , Catecóis/farmacologia , Catecóis/uso terapêutico , Álcoois Graxos/farmacologia , Álcoois Graxos/uso terapêutico , Álcoois Graxos/química , Extratos Vegetais/química , Zingiber officinale/química , Zingiber officinale/metabolismo
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