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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 319: 124564, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38824756

RESUMO

In our research we explore the world of PACDs, carbon dots synthesized from pamoic acid through a single step pyrolysis method. Our findings reveal that PACDs have capabilities of serving as sensitive and selective sensors in both colorimetric and fluorescent modes. They are particularly effective, at colorimetrically and fluorometrically detecting ferric ions and can also act as fluorometric sensors for pH. When ferric ions are introduced an interesting transformation occurs. A noticeable change in color unfolds before our eyes, under 365 nm UV light the fluorescence shifts from green to blue while in daylight it changes from a yellow to a deep ink blue. Notably these detection techniques can precisely measure ferric ions within concentrations ranging from 5 µM to 80 µM with a detection limit of 0.1 µM for fluorescence response. Additionally, they can detect ferric ions colorimetrically within the range of 5 µM to 45 µM with a detection limit of 3.8 µM. Furthermore, the PACDs exhibit a capability to adapt to different pH levels. In alkaline environments with a pH range between 8 and 11 the fluorescence signal demonstrates a response that directly correlates with pH levels and slightly shifts its position. In contrast under acidic conditions a noticeable shift, towards blue is observed in the fluorescence signal leading to a change in color from green to blue when exposed to UV light. This shift persists as the fluorescence signal directly correlates with decreasing pH levels in settings. Apart from their proficiency in ferric ion detection and pH monitoring, the PACDs also demonstrate potential in cancer research. Through an assessment using the MTT assay it was discovered that the PACDs exhibit cytotoxic effects against five different cancer cell lines; HCT 116, MDA MB 231, Hep3B, MCF 7 and HeLa. The findings are promising as the PACDs show IC50 values of 12.5 µg/ml 6.25 µg/ml 25 µg/ml 50 µg/ml and 100 µg/ml for these cell lines. This research highlights the versatility and potential of PACDs as a tool, in both sensing applications and oncology research.


Assuntos
Carbono , Pontos Quânticos , Espectrometria de Fluorescência , Humanos , Carbono/química , Pontos Quânticos/química , Concentração de Íons de Hidrogênio , Colorimetria/métodos , Limite de Detecção , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/análise
2.
Eur J Pharmacol ; 975: 176637, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38729416

RESUMO

Macrophages play a pivotal role in safeguarding against a broad spectrum of infections, from viral, bacterial, fungal to parasitic threats and contributing to the immune defense against cancer. While morphine's immunosuppressive effects on immune cells are extensively documented, a significant knowledge gap exists regarding its influence on macrophage polarization and differentiation. Hence, we conducted a study that unveils that prior exposure to morphine significantly impedes the differentiation of bone marrow cells into macrophages. Furthermore, the polarization of macrophages toward the M1 phenotype under M1-inducing conditions experiences substantial impairment, as evidenced by the diminished expression of CD80, CD86, CD40, iNOS, and MHCII. This correlates with reduced expression of M1 phenotypical markers such as iNOS, IL-1ß, and IL-6, accompanied by noticeable morphological, size, and phagocytic alterations. Further, we also observed that morphine affected M2 macrophages. These findings emphasize the necessity for a more comprehensive understanding of the impact of morphine on compromising macrophage function and its potential ramifications for therapeutic approaches.


Assuntos
Diferenciação Celular , Imunossupressores , Macrófagos , Morfina , Morfina/farmacologia , Animais , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Diferenciação Celular/efeitos dos fármacos , Imunossupressores/farmacologia , Polaridade Celular/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/metabolismo , Camundongos Endogâmicos C57BL , Fagocitose/efeitos dos fármacos , Ativação de Macrófagos/efeitos dos fármacos , Masculino , Interleucina-1beta/metabolismo
3.
Mini Rev Med Chem ; 24(13): 1238-1251, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38185891

RESUMO

BACKGROUND: Heterocyclic compounds and their derivatives play a significant role in the design and development of novel quinoline drugs. Among the various pharmacologically active heterocyclic compounds, quinolines stand out as the most significant rings due to their broad pharmacological roles, specifically antitubercular activity, and their presence in plant-based compounds. Quinoline is also known as benzpyridine, benzopyridine, and 1-azanaphthalene. It has a benzene ring fused with a pyridine ring, and both rings share two carbon atoms. The importance of quinoline lies in its incorporation as a key component in various natural compounds found in medicinal plant families like Fumariaceae, Berberidaceae, Rutaceae, Papavaraceae, and others. OBJECTIVE: This article is expected to have a significant impact on the advancement of effective antitubercular drugs. Through harnessing the potent activity of quinoline derivatives, the research aims to make valuable contributions to combating tuberculosis more efficiently and ultimately reducing the global burden of this infectious disease. METHODS: Numerous nitrogen-containing heterocyclic compounds exhibit significant potential as antitubercular agents. These chemicals have fused aromatic nitrogen-heterocyclic nuclei that can change the number of electrons they have, which can change their chemical, physical, and biological properties. This versatility comes from their ability to bind with the receptors in multiple modes, a critical aspect of drug pharmacological screening. Among these compounds, quinoline stands out as it incorporates a stable fusion of a benzene ring with a pyridine nucleus. Quinolines have demonstrated a diverse range of pharmacological activities, including but not limited to anti-tubercular, anti-tumor, anticoagulant, anti-inflammatory, antioxidant, antiviral, antimalarial, anti-HIV, and antimicrobial effects. RESULTS: Some molecules, such as lone-paired nitrogen species, include pyrrole, pyrazole, and quinoline. These molecules contain nitrogen and take part in metabolic reactions with other molecules inside the cell. However, an excessive accumulation of reactive nitrogen species can lead to cytotoxicity, resulting in damage to essential biological macromolecules. Among these compounds, quinoline stands out as the oldest and most effective one, exhibiting a wide range of significant properties such as antitubercular, antimicrobial, anti-inflammatory, antioxidant, analgesic, and anticonvulsant activities. Notably, naturally occurring quinoline compounds, such as quinine, have proven to be potent antimalarial drugs. CONCLUSION: This review highlights quinoline derivatives' antitubercular potential, emphasizing recent research advancements. Utilizing IC50 values, the study emphasizes the efficacy of various quinoline substitutions, hybrids, and electron-withdrawing groups against MTB H37Rv. Continued research is essential for developing potent, low-toxicity quinoline derivatives to combat tuberculosis.


Assuntos
Antituberculosos , Quinolinas , Quinolinas/química , Quinolinas/farmacologia , Antituberculosos/farmacologia , Antituberculosos/química , Humanos , Mycobacterium tuberculosis/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Animais , Estrutura Molecular
4.
Cureus ; 15(4): e37914, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37220467

RESUMO

Soft tissue chondroma is a relatively rare, slowly growing, benign cartilaginous tumor. This solitary mass can imitate chondrosarcomas in radiologic and histological characteristics. The diagnosis is hard to establish on clinical presentation and relies on careful radiological examination. The lesion is equally prevalent in both genders and primarily affects people in their forties and sixties. They may occur in any part of the body; however, they are most commonly observed in hand and foot. We report the case of a 61-year-old female who presented with heavily ossified soft tissue chondroma within the plantar fascia of her left foot. A conclusive diagnosis was established via histopathological examination. The chondroma was marginally excised, and the postoperative period was uneventful.

5.
Chin J Integr Med ; 29(6): 549-555, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37017881

RESUMO

Tinospora cordifolia (Guduchi or Gurjo), a herbaceous vine or climbing deciduous shrub, is consider as an important medicine in the Ayurvedic system of medication, which is available in India, China, Myanmar, Bangladesh and Srilanka. Menispermaceae is the family of this compound. T. cordifolia have a variety of properties to treat various ailments such as fevers, jaundice, diabetes, dysentery, urinary infections, and skin diseases. This compound has been subjected to many chemicals, pharmacological, pre-clinical, or clinical investigations and some new therapeutic potential effects have been indicated. This review aims to summarize the critical information concerning in areas of chemical constituents, chemical structure, and pharmacokinetic activities such as anti-diabetic, anticancer, immune-modulatory, antivirus (especially in silico study about COVID-19), antioxidant, antimicrobial, hepatoprotective and its effect on cardiovascular and neurological disorders as well as rheumatoid arthritis. This traditional herb needs more experimental study on the clinical, pre-clinical study, and clinical efficacy of these compounds for the prevention and treatment of COVID-19 and needs large-scale clinical studies to prove the clinical efficacy of this compound, especially in stress-related diseases and other neuronal disorders.


Assuntos
COVID-19 , Tinospora , Humanos , Tinospora/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/química , Antioxidantes/farmacologia , Antioxidantes/química
6.
Molecules ; 28(5)2023 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-36903437

RESUMO

Therapeutics, based on small interfering RNA (siRNA), have demonstrated tremendous potential for treating cancer. However, issues such as non-specific targeting, premature degradation, and the intrinsic toxicity of the siRNA, have to be solved before they are ready for use in translational medicines. To address these challenges, nanotechnology-based tools might help to shield siRNA and ensure its specific delivery to the target site. Besides playing a crucial role in prostaglandin synthesis, the cyclo-oxygenase-2 (COX-2) enzyme has been reported to mediate carcinogenesis in various types of cancer, including hepatocellular carcinoma (HCC). We encapsulated COX-2-specific siRNA in Bacillus subtilis membrane lipid-based liposomes (subtilosomes) and evaluated their potential in the treatment of diethylnitrosamine (DEN)-induced hepatocellular carcinoma. Our findings suggested that the subtilosome-based formulation was stable, releasing COX-2 siRNA in a sustained manner, and has the potential to abruptly release encapsulated material at acidic pH. The fusogenic property of subtilosomes was revealed by FRET, fluorescence dequenching, content-mixing assay, etc. The subtilosome-based siRNA formulation was successful in inhibiting TNF-α expression in the experimental animals. The apoptosis study indicated that the subtilosomized siRNA inhibits DEN-induced carcinogenesis more effectively than free siRNA. The as-developed formulation also suppressed COX-2 expression, which in turn up-regulated the expression of wild-type p53 and Bax on one hand and down-regulated Bcl-2 expression on the other. The survival data established the increased efficacy of subtilosome-encapsulated COX-2 siRNA against hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/patologia , Dietilnitrosamina/farmacologia , RNA Interferente Pequeno/farmacologia , Ciclo-Oxigenase 2 , Apoptose , Carcinogênese
7.
J Int Soc Prev Community Dent ; 13(6): 469-476, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38304537

RESUMO

Aim: To quantify and compare the metal ions released from different bracket-wire combinations and to assess their cytotoxicity. Materials and Methods: A total of 360 fabricated sectional fixed orthodontic appliances were divided into 6 groups. The first three groups consisted of stainless-steel brackets with stainless-steel, snickel-titanium (NiTi), and titanium-molybdenum alloy (TMA) archwires, and the other three groups were fabricated using ceramic brackets (polycrystalline alumina) with stainless-steel, NiTi, and TMA archwires. These appliances were immersed in artificial saliva (pH 6.5 ± 0.5, 37°C), for 1 week, 2 weeks, and 1 month. The nickel and chromium ions released in the artificial saliva were quantified using a flame atomic absorption spectrometer, and cytotoxicity assessment was performed using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay on human cervical cancer cell line. Results: The stainless-steel bracket groups displayed a significantly greater release of nickel and chromium ions compared to the ceramic bracket groups (P < 0.05). However, no significant differences were identified when comparing the three archwire types within the stainless-steel/ceramic bracket groups. At the end of 1 month, the % cell viability demonstrated by the appliances was in the decreasing order of stainless-steel-TMA > ceramic-stainless steel > stainless-steel-NiTi > ceramic-NiTi > stainless-steel-stainless steel > ceramic-TMA. Conclusion: Considerably greater release of nickel and chromium ions was observed from the appliances utilizing stainless-steel brackets compared to those employing ceramic brackets. However, no remarkable difference in the levels of nickel and chromium ions was observed when comparing the three archwires: stainless steel, NiTi, and TMA. In the cytotoxicity assessment, the ceramic-TMA combination displayed the highest level of cytotoxicity, while the stainless-steel-TMA combination displayed the least cytotoxicity.

8.
Cureus ; 14(11): e31753, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36569738

RESUMO

Eosinophilic granulomatosis with polyangiitis is a systemic vasculitis characterized by the presence of asthma, hyper-eosinophilia, and necrotizing vasculitis with extravascular eosinophilic granulomas. We report the case of a 25-year-old male who presented to the outpatient department complaining of joint aches and numbness in the hands and legs. Physical examination revealed erythematous blanchable macular rashes on palms and soles. Raynaud's phenomenon was also observed. Lab workup revealed elevated WBC count and peripheral blood eosinophilia. Antibody tests were positive only for anti-nuclear antibodies. A diagnosis of eosinophilic granulomatosis with polyangiitis including peripheral neuropathy, arthralgia, rash, and pulmonary manifestations was established. The patient was started on a therapeutic regimen of corticosteroids and immunosuppressants, which halted the progression of the disease. Peripheral neuropathy and arthralgia also improved.

9.
Cureus ; 14(11): e31946, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36582566

RESUMO

Schwannoma of the ascending colon is an extremely rare neoplasm that is often discovered incidentally in the asymptomatic older population on surveillance colonoscopy. We present the case of a symptomatic 22-year-old male presenting with one month of discomfort in the right lower abdominal quadrant, abdominal bloating, and hematochezia. A sessile polyp measuring 0.5 cm was identified in the ascending colon on the colonoscopy. The polyp was completely resected using cold snare polypectomy. Histological examination of the resected polyp with hematoxylin-eosin staining revealed small nodules of bland spindle cells with focal nuclear condensation. The lesional cells tested positive for S-100 and SOX-10 on immunohistochemical analysis, establishing the diagnosis of benign schwannoma. Since this lesion was submucosal, its diagnosis required an endoscopic biopsy that could only be performed on the mucosa. It was difficult to distinguish it from other mesenchymal tumors (gastrointestinal stromal tumor or leiomyoma), and this makes the differential diagnosis exceedingly challenging. If the immunohistochemistry is positive for S-100 and negative for C-KIT, CD-34, actin, and desmin, it aids in diagnosis. These tumors have non-specific radiological features and are asymptomatic.

10.
Front Genet ; 13: 1022734, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338993

RESUMO

Tumorigenesis is a multifaceted process, where multiple physiological traits serving as cancer's distinctive characteristics are acquired. "Hallmarks of cancer" is a set of cognitive abilities acquired by human cells that are pivotal to their tumor-forming potential. With limited or no protein-coding ability, non-coding RNAs (ncRNAs) interact with their target molecules and yield significant regulatory effects on several cell cycle processes. They play a "yin" and "yang" role, thereby functioning both as oncogenic and tumor suppressor and considered important in the management of various types of cancer entities. ncRNAs serve as important post-transcriptional and translational regulators of not only unrestricted expansion and metastasis of tumor cells but also of various biological processes, such as genomic mutation, DNA damage, immune escape, and metabolic disorder. Dynamical attributes such as increased proliferative signaling, migration, invasion, and epithelial-mesenchymal transition are considered to be significant determinants of tumor malignancy, metastatic dissemination, and therapeutic resistance. Furthermore, these biological attributes engage tumor cells with immune cells within the tumor microenvironment to promote tumor formation. We elaborate the interaction of ncRNAs with various factors in order to regulate cancer intra/intercellular signaling in a specific tumor microenvironment, which facilitates the cancer cells in acquiring malignant hallmarks. Exosomes represent a means of intercellular communication and participate in the maintenance of the tumor hallmarks, adding depth to the intricate, multifactorial character of malignant neoplasia. To summarize, ncRNAs have a profound impact on tumors, affecting their microcirculation, invasiveness, altered metabolism, microenvironment, and the capacity to modify the host immunological environment. Though the significance of ncRNAs in crosstalk between the tumor and its microenvironment is being extensively explored, we intend to review the hallmarks in the light of exosome-derived non-coding RNAs and their impact on the tumor microenvironment.

11.
Steroids ; 188: 109113, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36152868

RESUMO

Zinc oxide nanoparticles (ZnO NPs) were synthesized by a green method using Azadirachta indica leaf extract. The structure of the prepared ZnO (NPs) were characterized by FT-IR, XRD, SEM-EDX and TEM analyses. The biosynthesized ZnO (NPs) were then used as a catalyst for the synthesis of steroidal dihydropyrazole derivatives through a one-pot multicomponent reaction involving phenyl acetylene and hydrazine derivatives. The anticancer activity of newly synthesized compounds were evaluated against three cancer cell lines namely HeLa (human cervical carcinoma), Hep3B (human hepatocellular carcinoma) and MCF7 (human breast adenocarcinoma) by MTT assay. The tested compounds were found to be active against all cancer cell lines and less toxic towards normal peripheral blood mononuclear cells (PBMCs). Antioxidant activity have also been investigated via free radical scavenging ability using DPPH, FRAP and ABTS assay. The tested compounds were found to exhibit moderate to good antioxidant activity which increases with increase in the concentration of steroidal dihydropyrazoles. Among all the tested steroidal dihydropyrazoles, compound 17 is found to be most active.


Assuntos
Nanopartículas Metálicas , Óxido de Zinco , Humanos , Óxido de Zinco/farmacologia , Óxido de Zinco/química , Antioxidantes/farmacologia , Antioxidantes/química , Testes de Sensibilidade Microbiana , Espectroscopia de Infravermelho com Transformada de Fourier , Leucócitos Mononucleares , Nanopartículas Metálicas/química , Extratos Vegetais/química
12.
Cancers (Basel) ; 15(1)2022 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-36612248

RESUMO

Phytochemicals possess various intriguing pharmacological properties against diverse pathological conditions. Extensive studies are on-going to understand the structural/functional properties of phytochemicals as well as the molecular mechanisms of their therapeutic function against various disease conditions. Phytochemicals such as curcumin (Cur), genistein (Gen), and tanshinone-IIA (Tan IIA) have multifaceted therapeutic potentials and various efforts are in progress to understand the molecular dynamics of their function with different tools and technologies. Cur is an active lipophilic polyphenol with pleiotropic function, and it has been shown to possess various intriguing properties including antioxidant, anti-inflammatory, anti-microbial, anticancer, and anti-genotoxic properties besides others beneficial properties. Similarly, Gen (an isoflavone) exhibits a wide range of vital functions including antioxidant, anti-inflammatory, pro-apoptotic, anti-proliferative, anti-angiogenic activities etc. In addition, Tan IIA, a lipophilic compound, possesses antioxidant, anti-angiogenic, anti-inflammatory, anticancer activities, and so on. Over the last few decades, the field of proteomics has garnered great momentum mainly attributed to the recent advancement in mass spectrometry (MS) techniques. It is envisaged that the proteomics technology has considerably contributed to the biomedical research endeavors lately. Interestingly, they have also been explored as a reliable approach to understand the molecular intricacies related to phytochemical-based therapeutic interventions. The present review provides an overview of the proteomics studies performed to unravel the underlying molecular intricacies of various phytochemicals such as Cur, Gen, and Tan IIA. This in-depth study will help the researchers in better understanding of the pharmacological potential of the phytochemicals at the proteomics level. Certainly, this review will be highly instrumental in catalyzing the translational shift from phytochemical-based biomedical research to clinical practice in the near future.

13.
Front Immunol ; 12: 706727, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777338

RESUMO

Tuberculosis (TB) is a significant and continuing problem worldwide, with a death toll of around 1.5 million human lives annually. BCG, the only vaccine against TB, offers a varied degree of protection among human subjects in different regions and races of the world. The majority of the population living near the tropics carries a varying degree of tolerance against BCG due to the widespread prevalence of non-tuberculous mycobacteria (NTM). Interestingly, ≈90% of the Mycobacterium tuberculosis (Mtb) infected population restrain the bacilli on its own, which strengthens the notion of empowering the host immune system to advance the protective efficacy of existing mycobacterial vaccines. In general, Mtb modulates IL-10/STAT3 signaling to skew host mononuclear phagocytes toward an alternatively activated, anti-inflammatory state that helps it thrive against hostile immune advances. We hypothesized that modulating the IL-10/STAT3 driven anti-inflammatory effects in mononuclear cells may improve the prophylactic ability of TB vaccines. This study investigated the immunotherapeutic ability of a porphyrin based small molecule inhibitor of IL-10/STAT3 axis, 5, 15-diphenyl porphyrin (DPP), in improving anti-TB immunity offered by second generation recombinant BCG30 (rBCG30-ARMF-II®) vaccine in mice. The DPP therapy potentiated vaccine induced anti-TB immunity by down-modulating anti-inflammatory responses, while simultaneously up-regulating pro-inflammatory immune effector responses in the immunized host. The employed DPP based immunotherapy led to the predominant activation/proliferation of pro-inflammatory monocytes/macrophages/DCs, the concerted expansion of CD4+/CD8+ effector and central memory T cells, alongside balanced Th17 and Treg cell amplification, and conferred augmented resistance to aerosol Mtb challenge in rBCG30 immunized BALB/c mice.


Assuntos
Vacina BCG/imunologia , Ativação de Macrófagos/imunologia , Macrófagos/imunologia , Mycobacterium tuberculosis/imunologia , Porfirinas/farmacologia , Tuberculose/imunologia , Animais , Vacina BCG/administração & dosagem , Plasticidade Celular/efeitos dos fármacos , Citocinas/metabolismo , Humanos , Imunização , Imunomodulação , Imunoterapia , Mediadores da Inflamação/metabolismo , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Células T de Memória/imunologia , Células T de Memória/metabolismo , Camundongos , Fagócitos/efeitos dos fármacos , Fagócitos/imunologia , Fagócitos/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Tuberculose/prevenção & controle
14.
J Basic Clin Physiol Pharmacol ; 33(3): 223-233, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33638319

RESUMO

N-acetylcysteine (NAC) is considered as the body's major antioxidant molecules with diverse biological properties. In this review, the pharmacokinetics, safety and efficacy report on both the preclinical and clinical summary of NAC is discussed. Both in vitro and in vivo preclinical studies along with the clinical data have shown that NAC has enormous biological properties. NAC is used in the treatment of acetaminophen poisoning, diabetic nephropathy, Alzheimer's disease, schizophrenia, and ulcerative colitis, etc. Numerous analytical techniques, for instance, UPLC, LC-MS, HPLC, RP-IPC are primarily employed for the estimation of NAC in different single and fixed-dose combinations. The molecular docking studies on NAC demonstrate the binding within Sudlow's site-I hydrogen bonds and formation of NAC and BSA complexes. Various hydrophobic and hydrophilic amino acids generally exist in making contact with NAC as NAC-BSA complexes. Docking studies of NAC with the active site of the urease exposed an O-coordinated bond through nickel 3002 and a hydrogen bond through His-138. NAC and its analogs also made the allosteric pockets that helped to describe almost all favorable pose for the chaperone in a complex through the protein. Thus, we intended to highlight the several health benefits of this antioxidant compound and applications in pharmaceutical product development.


Assuntos
Acetilcisteína , Antioxidantes , Acetilcisteína/metabolismo , Acetilcisteína/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Cromatografia Líquida de Alta Pressão , Composição de Medicamentos , Simulação de Acoplamento Molecular
15.
Front Aging ; 2: 748591, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35822018

RESUMO

During the last 2 years, the entire world has been severely devastated by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic (COVID-19) as it resulted in several million deaths across the globe. While the virus infects people indiscriminately, the casualty risk is higher mainly in old, and middle-aged COVID-19 patients. The incidences of COVID-19 associated co-morbidity and mortality have a great deal of correlation with the weakened and malfunctioning immune systems of elderly people. Presumably, due to the physiological changes associated with aging and because of possible comorbidities such as diabetes, hypertension, obesity, cardiovascular, and lung diseases, which are more common in elderly people, may be considered as the reason making the elderly vulnerable to the infection on one hand, and COVID-19 associated complications on the other. The accretion of senescent immune cells not only contributes to the deterioration of host defense, but also results in elevated inflammatory phenotype persuaded immune dysfunction. In the present review, we envisage to correlate functioning of the immune defense of older COVID-19 patients with secondary/super infection, increased susceptibility or aggravation against already existing cancer, infectious, autoimmune, and other chronic inflammatory diseases. Moreover, we have discussed how age-linked modulations in the immune system affect therapeutic response against administered drugs as well as immunological response to various prophylactic measures including vaccination in the elderly host. The present review also provides an insight into the intricate pathophysiology of the aging and the overall immune response of the host to SARS-CoV-2 infection. A better understanding of age-related immune dysfunction is likely to help us in the development of targeted preemptive strategies for deadly COVID-19 in elderly patients.

16.
J Biomol Struct Dyn ; 39(11): 4037-4050, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32496965

RESUMO

Currently, most pathogens influencing a number of epidemics outline a notable warning to human health. It has pushed researchers to design new antimicrobial drugs using transition metals that are studied in proceeding fewer years for their antimicrobial properties. Henceforth, in this work, two mononuclear complexes [Imz-H][Fe(pda)2]⋅1⋅3H2O (1) and [Mn(Imz)6]⋅2Cl-⋅2H2O (2) [Imz = imidazole and H2pda = 2,6 pyridine dicarboxylic acid] are isolated and characterized systematically by various spectral and single-crystal XRD studies. The antimicrobial activity of the present hexadentate complexes of Fe(III) and Mn(II) against Gram-positive as well as Gram-negative bacteria is also assessed. Augmented activity against standard isolates of Staphylococcus aureus with a minimum inhibitory concentration (MIC) is observed. Similar activity was also observed toward Escherichia coli, Klebsiella pneumoniae and Listeria monocytogenes. 1 and 2 have excellent bactericidal activity, and no resistant mutant for S. aureus was seen. The compound also unveiled antibiofilm activity and was capable to disrupt significantly the pre-formed biofilms and this property was confirmed by XTT assay experiment. The MTT assay data indicate that 1 and 2 can be used as anticancer agents toward the RAW 64.7 (human macrophage/monocyte) cell line. Further, the molecular docking study reveals that the role of imidazole is very important in the biological activity of these complexes. Moreover, our results suggest that 1 and 2 with its effective anti-microbial, anti-biofilm and cytotoxicity activity can be used to treat bacterial and fungal infections and could be appraised clinically for further applications.Communicated by Ramaswamy H. Sarma.


Assuntos
Anti-Infecciosos , Listeria monocytogenes , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Compostos Férricos , Humanos , Imidazóis/farmacologia , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Staphylococcus aureus
17.
Nanomaterials (Basel) ; 10(6)2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32492878

RESUMO

A novel method of preparing reduced graphene oxide (RGOX) from graphene oxide (GOX) was developed employing vegetable extract, Chenopodium album, as a reducing and stabilizing agent. Chenopodium album is a green leafy vegetable with a low shelf life, fresh leaves of this vegetable are encouraged to be used due to high water content. The previously modified 'Hummers method' has been in practice for the preparation of GOX by using precursor graphite powder. In this study, green synthesis of RGOX was functionally verified by employing FTIR and UV-visible spectroscopy, along with SEM and TEM. Our results demonstrated typical morphology of RGOX stacked in layers that appeared as silky, transparent, and rippled. The antibacterial activity was shown by analyzing minimal inhibitory concentration values, agar diffusion assay, fluorescence techniques. It showed enhanced antibacterial activity against Gram-positive and Gram-negative bacteria in comparison to GOX. It has also been shown that the synthesized compound exhibited enhanced antibiofilm activity as compared to its parent compound. The efficacy of RGOX and GOX has been demonstrated on a human breast cancer cell line, which suggested RGOX as a potential anticancer agent.

18.
Front Chem ; 7: 787, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31799242

RESUMO

In general, neurodegenerative disorders have a great deal of correlation with the misfolded as well as aggregated forms of protein-based macromolecules. Among various species formed during the aggregation process, protein oligomers have been classified as most toxic entities against several types of living cells. A series of chemicals have been developed to inhibit protein aggregation as a measure to regulate neurodegenerative diseases. Recently, various classes of nanoparticles have also been reported to inhibit protein aggregation. In the present study, we synthesized fluorescent gold nanoparticles (B-AuNPs) employing Olax scandens leaf extract. Next, an in vitro study was performed to assess the effect of as-synthesized B-AuNPs on the aggregation behavior of the ovalbumin (OVA) and other related model proteins. We performed an extensive study to elucidate anti-amyloidogenic properties of nano-sized entities and established that small-sized B-AuNPs manifest chaperone potential against protein aggregation. Further, we exploited as-synthesized B-AuNPs as a mean to prevent protein aggregation mediated toxicity in neuroblastoma cells.

19.
Photochem Photobiol Sci ; 18(12): 3008-3015, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31696896

RESUMO

A quinoline moiety was used as a building block for designing a probe for the selective detection of copper ions in a partially aqueous medium. We have developed a molecular sensing system which gives insight into the complex physiological and redox aspects of labile copper. The probe provides a colorimetric approach for distinguishing cuprous and cupric ions along with their simultaneous discrimination from other metal ions in the visible range of the spectrum. The chemosensor showed a remarkable fluorescence enhancement along with a significant bathochromic shift of about 35 nm. The detection limit of the probe was found to be 1.03 µM which is optimally favorable to be applied in real-time monitoring. Fabrication of paper strips with the probe was done to detect the presence of cuprous ions in the real sample. The value of the binding constant (1.37 × 104 M-1) suggests stable complex formation between the metal ion and the sensing probe. The photoluminescence and structural aspects of the chemosensor were characterized by using fluorescence, absorption, ESI-MS, and 1H NMR spectroscopy. Furthermore, the cytotoxic nature and bioimaging properties of the probe were interpreted in vitro on RAW 264.7 macrophage cell lines and peripheral blood mononuclear cells (PBMCs) respectively.


Assuntos
Colorimetria , Cobre/análise , Quinolinas/química , Animais , Corantes Fluorescentes/química , Humanos , Íons/química , Leucócitos Mononucleares/química , Leucócitos Mononucleares/citologia , Limite de Detecção , Macrófagos/química , Macrófagos/citologia , Camundongos , Microscopia de Fluorescência , Células RAW 264.7
20.
J Cell Physiol ; 234(5): 6951-6964, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30443899

RESUMO

In the recent past, various groups have proposed diverse biocompatible methods for the synthesis of metal nanoparticles (NPs). Besides culture biomass, culture supernatants (CS) are increasingly being explored for the synthesis of NPs; however, with the ever-increasing exploration of various CS in the biofabrication of NPs, it is equally important to explore the potential of various culture media (CMs) in the synthesis of metal NPs. Considering these aspects, in the present investigation, we explore the possible applicability of various CMs in the biofabrication of metal NPs. The synthesis of NPs was primarily followed by UV/VIS spectroscopy, and, thereafter, the NPs were characterized by various physiochemical techniques, including EM, EDX, FT_IR, X-ray diffraction, and DLS measurements, and finally, their anticancer potentialities were investigated against breast cancer. In addition, the NPs were examined in conjunction with artemisinin for therapeutic benefits against aggressive and highly metastatic MDA-MB-231 breast cancer cells. Cumulatively, the results of the present study collated the potentials of various bacterial CMs in the biofabrication of metal NPs and ascertained the efficacy of the as-synthesized silver nanoparticles, especially the combinatorial entity as intriguing breast cancer therapeutics. The data of the present study plausibly assist in advancing the therapeutic applicability of the combinatorial amalgam against aggressive and highly metastatic MDA-MB-231 breast cancer cells.


Assuntos
Artemisininas/química , Artemisininas/farmacologia , Bactérias/metabolismo , Neoplasias da Mama/tratamento farmacológico , Meios de Cultura/metabolismo , Nanopartículas Metálicas/química , Antineoplásicos/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , Feminino , Células HEK293 , Humanos , Células MCF-7 , Tamanho da Partícula , Prata/química
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