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1.
J Chromatogr Sci ; 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38706312

RESUMO

Glycyrrhiza glabra is commonly known as licorice. Licorice is the major source of glycyrrhizin. There is no reported stability indicating method for glycyrrhizin in the literature so far. Therefore, it was proposed to develop a stability indicating method and validate the method for glycyrrhizin and its application in G. glabra root extract. Method validation parameters were performed as per the International Council for Harmonization guidelines. The chromatographic separation was achieved on a Zorbax Extended C-18 (250 × 4.6 mm, 5 µm) column. The separation achieved using the mobile phase consisted of 0.1% formic acid in water and acetonitrile in gradient elution. The flow rate was kept at 1 mL/min, and ultraviolet-visible spectroscopy detection was at 250 nm. The average retention time of glycyrrhizin was found to be 7.30 min. Stress degradation studies were performed and confirmed that only acidic degradation has shown a degradation profile of glycyrrhizin up to 40%. The percentage of glycyrrhizin was found to be 0.40% in the G. glabra extract. This may be further explored for commercial applications.

2.
Indian J Otolaryngol Head Neck Surg ; 76(2): 2166-2170, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38566724

RESUMO

Perioperative high dose rate brachytherapy involves insertion of brachytherapy catheter over the tumor bed during surgical removal of disease followed by radiation in the postoperative period. It has applications in radiotherapy dose escalation or reirradiation and for extending the surgical margins. We report here initial results of treatment in five cases of locally advanced head and neck cancers.

3.
Exp Gerontol ; 189: 112409, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38522483

RESUMO

Among all non-communicable diseases, Cardiovascular Diseases (CVDs) stand as the leading global cause of mortality. Within this spectrum, Myocardial Infarction (MI) strikingly accounts for over 15 % of all deaths. The intricate web of risk factors for MI, comprising family history, tobacco use, oral health, hypertension, nutritional pattern, and microbial infections, is firmly influenced by the human gut and oral microbiota, their diversity, richness, and dysbiosis, along with their respective metabolites. Host genetic factors, especially allelic variations in signaling and inflammatory markers, greatly affect the progression or severity of the disease. Despite the established significance of the human microbiome-nutrient-metabolite interplay in associations with CVDs, the unexplored terrain of the gut-heart-oral axis has risen as a critical knowledge gap. Moreover, the pivotal role of the microbiome and the complex interplay with host genetics, compounded by age-related changes, emerges as an area of vital importance in the development of MI. In addition, a distinctive disease susceptibility and severity influenced by gender-based or ancestral differences, adds a crucial insights to the association with increased mortality. Here, we aimed to provide an overview on interactions of microbiome (oral and gut) with major risk factors (tobacco use, alcohol consumption, diet, hypertension host genetics, gender, and aging) in the development of MI and therapeutic regulation.


Assuntos
Microbioma Gastrointestinal , Hipertensão , Microbiota , Infarto do Miocárdio , Humanos , Fatores de Risco
4.
Mol Cell ; 84(6): 1149-1157.e7, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38309274

RESUMO

OCA-B, OCA-T1, and OCA-T2 belong to a family of coactivators that bind to POU transcription factors (TFs) to regulate gene expression in immune cells. Here, we identify IκBζ (encoded by the NFKBIZ gene) as an additional coactivator of POU TFs. Although originally discovered as an inducible regulator of NF-κB, we show here that IκBζ shares a microhomology with OCA proteins and uses this segment to bind to POU TFs and octamer-motif-containing DNA. Our functional experiments suggest that IκBζ requires its interaction with POU TFs to coactivate immune-related genes. This finding is reinforced by epigenomic analysis of MYD88L265P-mutant lymphoma cells, which revealed colocalization of IκBζ with the POU TF OCT2 and NF-κB:p50 at hundreds of DNA elements harboring octamer and κB motifs. These results suggest that IκBζ is a transcriptional coactivator that can amplify and integrate the output of NF-κB and POU TFs at inducible genes in immune cells.


Assuntos
DNA , NF-kappa B , NF-kappa B/genética , NF-kappa B/metabolismo , Regiões Promotoras Genéticas , DNA/genética , DNA/metabolismo
5.
Cell Mol Biol Lett ; 29(1): 13, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38225560

RESUMO

TRIM proteins are characterized by their conserved N-terminal RING, B-box, and coiled-coil domains. These proteins are efficient regulators of autophagy, apoptosis, and innate immune responses and confer immunity against viruses and bacteria. TRIMs function as receptors or scaffold proteins that target substrates for autophagy-mediated degradation. Most TRIMs interact with the BECN1-ULK1 complex to form TRIMosomes, thereby efficiently targeting substrates to autophagosomes. They regulate the functions of ATG proteins through physical interactions or ubiquitination. TRIMs affect the lipidation of MAP1LC3B1 to form MAP1LC3B2, which is a prerequisite for phagophore and autophagosome formation. In addition, they regulate MTOR kinase and TFEB, thereby regulating the expression of ATG genes. TRIM proteins are efficient regulators of apoptosis and are crucial for regulating cell proliferation and tumor formation. Many TRIM proteins regulate intrinsic and extrinsic apoptosis via the cell surface receptors TGFBR2, TNFRSF1A, and FAS. Mitochondria modulate the anti- and proapoptotic functions of BCL2, BAX, BAK1, and CYCS. These proteins use a multipronged approach to regulate the intrinsic and extrinsic apoptotic pathways, culminating in coordinated activation or inhibition of the initiator and executor CASPs. Furthermore, TRIMs can have a dual effect in determining cell fate and are therefore crucial for cellular homeostasis. In this review, we discuss mechanistic insights into the role of TRIM proteins in regulating autophagy and apoptosis, which can be used to better understand cellular physiology. These findings can be used to develop therapeutic interventions to prevent or treat multiple genetic and infectious diseases.


Assuntos
Proteínas Reguladoras de Apoptose , Apoptose , Proteínas com Motivo Tripartido/química , Proteínas com Motivo Tripartido/metabolismo , Ubiquitinação , Autofagia
6.
Artigo em Inglês | MEDLINE | ID: mdl-38275062

RESUMO

BACKGROUND: Recognizing the potential of the immune system, immunotherapies have brought about a revolution in the treatment of cancer. Low tumour mutational burden and strong immunosuppression in the peritoneal tumor microenvironment (TME) lead to poor outcomes of immune checkpoint inhibition (ICI) and CART cell therapy in ovarian cancer. Alternative immunotherapeutic strategies are of utmost importance to achieve sound clinical success. INTRODUCTION: The development of peptide vaccines based on tumor-associated antigens (TAAs) for ovarian cancer cells can be a potential target to provoke an anti-tumor immune response and subsequent clearance of tumour cells. The purpose of this in-silico study was to find potential epitopes for a multi-epitope vaccine construct using the immunopeptidomics landscape of ovarian carcinoma. METHODS: The four TAAs (MUC16, IDO1, FOLR1, and DDX5) were selected as potential epitopes for B-cells, helper T-lymphocytes (HTLs), and cytotoxic T-lymphocytes (CTLs) predicted on the basis of antigenic, allergenic, and toxic properties. These epitopes were combined with suitable linkers and an adjuvant to form a multi-epitope construct. RESULTS: Four HTLs, 13 CTLs, and 6 potential B-cell epitopes were predicted from the TAAs. The designed multi-epitope construct was potentially immunogenic, non-toxic, and nonallergenic. Physicochemical properties and higher-order structural analyses of the final construct revealed a potential vaccine candidate. CONCLUSION: The designed vaccine construct has the potential to trigger both humoral and cellular immune responses and may be employed as a therapeutic immunization candidate for ovarian malignancies. However, further in vitro and animal experimentation is required to establish the efficacy of the vaccine candidate.

7.
Am J Transplant ; 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38219868

RESUMO

Atezolizumab plus bevacizumab is the preferred first-line treatment regimen for patients with advanced hepatocellular carcinoma. Limited data have shown promising results with the use of immune checkpoint inhibitors like nivolumab to downstage these patients for liver transplantation (LT). Here, we describe the first case of successful downstaging with atezolizumab plus bevacizumab in a patient with multifocal hepatocellular carcinoma and main portal vein tumoral thrombosis, followed by ABO-incompatible live donor LT. This illustrated case highlights that atezolizumab plus bevacizumab therapy may be a potential bridging tool for curative LT.

8.
Vet Res Commun ; 48(2): 849-863, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37957451

RESUMO

The effect of the insulin-sensitizing drug metformin on preovulatory follicle (POF) number, ovulation rate, fetal rate and prolificacy was studied in forty-six cyclic Malpura ewes. After estrus synchronization, the ewes were equally divided into two groups (n = 23). The treatment group (MET) received a daily oral dose of metformin at a rate of 500 mg/animal for approximately 12 weeks, spanning five estrous cycles, as against untreated control (CON). All the ewes were bred to proven rams at the end of treatment. Ovarian ultrasound scans were performed at each estrus and day 9 of each cycle to assess the number and diameter of POFs and corpora lutea (CL), respectively. A comprehensive assessment of circulating hormones including, estradiol, progesterone, androstenedione, and insulin as well as metabolic indicators such as glucose, and lipid profile parameters was performed. At the end of treatment on the day of estrus (E5D0), the treatment showed a stimulatory effect on follicular development with a 53.2% (P < 0.001) increase in the number of POFs. It also increased the ovulation rate by 67.4% (P < 0.01), with a higher proportion (χ2df1 = 10.7, P < 0.001) of ewes in the MET group having multiple ovulations compared to the CON group (82.6 vs. 30.4%). With 1.48 ± 0.12 prolificacy rate in MET ewes, the proportion of ewes giving birth to multiple lambs was 2.9-fold higher than in the CON group. Plasma estradiol, insulin, glucose, total cholesterol, and LDL-cholesterol concentrations were lower (P < 0.05) in the MET ewes than in the CON. The results of the present study indicate that metformin can increase the number of POF, ovulation rate, fetal rate and prolificacy in ewes, while reducing the plasma estradiol, insulin, glucose and cholesterol in MET ewes.


Assuntos
Insulina , Metformina , Ovinos , Animais , Gravidez , Feminino , Masculino , Insulina/farmacologia , Ovulação , Progesterona/farmacologia , Estradiol/farmacologia , Carneiro Doméstico , Colesterol/farmacologia , Glucose/farmacologia , Metformina/farmacologia
9.
ACS Pharmacol Transl Sci ; 6(12): 1801-1816, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38093838

RESUMO

Hepatocellular carcinoma (HCC) remains one of the predominant causes of cancer-related mortality across the globe. It is attributed to obesity, excessive alcohol consumption, smoking, and infection by the hepatitis virus. Early diagnosis of HCC is essential, and local treatments such as surgical excision and percutaneous ablation are effective. Palliative systemic therapy, primarily with the tyrosine kinase inhibitor Sorafenib, is used in advanced cases. However, the prognosis for advanced HCC remains poor. This Review additionally describes the pathophysiological mechanisms of HCC, which include aberrant molecular signaling, genomic instability, persistent inflammation, and the paradoxical position of the immune system in promoting and suppressing HCC. The paper concludes by discussing the growing body of research on the relationship between mitochondria and HCC, suggesting that mitochondrial dysfunction may contribute to the progression of HCC. This Review focuses on immunological interactions between different mechanisms of HCC progression, including obesity, viral infection, and alcohol consumption.

10.
Indian J Plast Surg ; 56(6): 548-551, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38105881

RESUMO

During nuclear disaster, infrastructure is severely damaged and injuries are often combined with trauma/burns and whole-body radiation. This makes triage difficult, especially when resources are severely deficient. To solve this problem, in this article, the authors have suggested a new less technology-dependent radiation dosimetry and quick triage using a specially designed triage matrix during nuclear disasters.

11.
Small ; : e2308639, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38126905

RESUMO

Next-generation cancer treatments are expected not only to target cancer cells but also to simultaneously train immune cells to combat cancer while modulating the immune-suppressive environment of tumors and hosts to ensure a robust and lasting response. Achieving this requires carriers that can codeliver multiple therapeutics to the right cancer and/or immune cells while ensuring patient safety. Nanotechnology holds great potential for addressing these challenges. This article highlights the recent advances in nanoimmunotherapeutic development, with a focus on breast cancer. While immune checkpoint inhibitors (ICIs) have achieved remarkable success and lead to cures in some cancers, their response rate in breast cancer is low. The poor response rate in solid tumors is often associated with the low infiltration of anti-cancer T cells and an immunosuppressive tumor microenvironment (TME). To enhance anti-cancer T-cell responses, nanoparticles are employed to deliver ICIs, bispecific antibodies, cytokines, and agents that induce immunogenic cancer cell death (ICD). Additionally, nanoparticles are used to manipulate various components of the TME, such as immunosuppressive myeloid cells, macrophages, dendritic cells, and fibroblasts to improve T-cell activities. Finally, this article discusses the outlook, challenges, and future directions of nanoimmunotherapeutics.

12.
Indian J Otolaryngol Head Neck Surg ; 75(4): 3585-3589, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37974868

RESUMO

AIMS: Obesity affects adverse outcomes in patients undergoing various surgeries. The study was carried out to assess the clinical association between body mass index and post tonsillectomy hemorrhages. MATERIALS AND METHODS: This prospective study was carried out on 60 patients, age between 5 and 40 years, admitted in Department of ENT with chronic tonsillitis. Body mass index and post tonsillectomy hemorrhage were evaluated in all patients who underwent surgery. Bleeding episode were categorized according to the Austrian tonsil study. RESULTS: This prospective study was carried out on 60 patients (adults and children), between December 2021 and November 2022. All patients underwent tonsillectomy under general anaesthesia. It was seen that most of the patients did not have any significant bleeding i.e., Grade A1 (Dry, no clot), and A2 (Clot, but no active bleeding after clot removal) whereas 4 patients (6.7%) had Grade B1 post tonsillectomy hemorrhage (Minimal bleeding requiring minimal intervention by vasoconstriction using adrenaline swab). Post tonsillectomy hemorrhage was seen more in adults. Post tonsillectomy bleeding of Grade B1 was recored in 28.6% of underweight patients, 8% of normal weight patients and no significant bleeding occurred in any of the overweight and obese patients (p-value 0.256). CONCLUSION: Overweight and obesity (higher BMI) did not increase the risk of post tonsillectomy hemorrhage in either children or adults.

13.
Int J Biol Macromol ; 253(Pt 6): 127260, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37802449

RESUMO

Cancer is a significant health hazard worldwide and poses a greater threat to the quality of human life. Quantifying cancer biomarkers with high sensitivity has demonstrated considerable potential for compelling, quick, cost-effective, and minimally invasive early-stage cancer detection. In line with this, efforts have been made towards developing an f-graphene@Ti3C2-MXene nanohybrid thin-film-based electrochemical biosensing platform for efficient carcinoembryonic antigen (CEA) detection. The air-brush spray coating technique has been utilized for depositing the uniform thin films of amine functionalized graphene (f-graphene) and Ti3C2-MXene nanohybrid on ITO-coated glass substrate. The chemical bonding and morphological studies of the deposited nanohybrid thin films are characterized by advanced analytical tools, including XRD, XPS, and FESEM. The EDC-NHS chemistry is employed to immobilize the deposited thin films with monoclonal anti-CEA antibodies, followed by blocking the non-specific binding sites with BSA. The electrochemical response and optimization of biosensing parameters have been conducted using CV and DPV techniques. The optimized BSA/anti-CEA/f-graphene@Ti3C2-MXene immunoelectrode showed the ability to detect CEA biomarker from 0.01 pg mL-1 to 2000 ng mL-1 having a considerably lower detection limit of 0.30 pg mL-1.


Assuntos
Técnicas Biossensoriais , Grafite , Neoplasias , Humanos , Biomarcadores Tumorais , Antígeno Carcinoembrionário/química , Grafite/química , Titânio/química , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas , Limite de Detecção
14.
Indian J Plast Surg ; 56(4): 388-389, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37705824
15.
Nanomedicine (Lond) ; 18(19): 1261-1279, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37721134

RESUMO

Aims: To develop an estrone-targeted d-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS)-based liposomal system for enhanced intracellular delivery of doxorubicin (DOX). Materials & methods: Zetasizer, transmission electron microscopy, energy dispersive x-ray, Fourier-transform infrared spectroscopy, differential scanning calorimetry, x-ray diffraction, confocal laser scanning microscopy and FACS analysis were used for formulation characterization and evaluation. Results: The DOX-LIPO-TPGS and DOX-LIPO-TPGS-estrone formulations had vesicle sizes (117.6 ± 3.51; 144 ± 5.00 nm), zeta potential (-36.4 ± 0.75; -35.8 ± 0.76), polydispersity index (0.123 ± 0.005; 0.169 ± 0.005) and percent entrapment efficiency (73.56 ± 3.55; 77.16 ± 3.83%) with improved cytotoxicity and cellular uptake, confirming the targeted potential of the developed formulations. Conclusion: The results suggest that the developed liposomal formulation with desired characteristics is potentially capable of nonimmunogenic, site-specific drug delivery to targeted cancer sites and reduced DOX-associated cardiac toxicity.


Doxorubicin (DOX) is an effective chemotherapy drug to treat breast cancer. However, DOX can cause unwanted side effects such as damage to the heart. This is due to side effects in healthy body tissues. This study was designed to develop nanoparticles that target cancer cells specifically to improve the delivery of DOX to these cells and prevent side effects elsewhere. Nanoparticles called liposomes were used as the platform for delivering DOX. Liposomes are sometimes coated with d-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS), a synthetic vitamin D derivative. This helps the liposome evade the immune system and release the drug more effectively. TPGS was tethered with estrone (ES), a type of estrogen. Certain breast cancer cells have many more estrogen receptors on their cell surface than healthy cells. TPGS-ES was coated on DOX-loaded liposomes to achieve enhanced intracellular delivery of DOX to breast cancer cells specifically. These liposomes were called DOX-LIPO-TPGS-ES. This liposome proved more toxic to cells in a breast cancer cell line than free DOX or liposomes without tethered ES. When tested in rats, DOX-LIPO-TPGS-ES showed increased tumor uptake compared with free DOX or liposomes without tethered ES. Rats treated with either liposomal drug showed normal levels of key markers associated with heart function, whereas those treated with free DOX showed increased levels of these markers. These results suggest that DOX-LIPO-TPGS-ES is capable of highly targeted delivery of DOX with limited side effects.

16.
Cureus ; 15(6): e39896, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37404432

RESUMO

Tuberculous meningitis is the most serious complication of tuberculosis. Early diagnosis is crucial to start relevant treatment to prevent death and disability. Electronic databases PubMed, Google Scholar, and Cochrane Library were used to find relevant articles from January 1980 to June 2022. The random-effect model in terms of pooled sensitivity, specificity, and diagnostic odds ratio (DOR) with 95% confidence interval was adopted to derive the diagnostic efficacy of cerebrospinal fluid (CSF) adenosine deaminase (ADA) for the diagnosis of tuberculous meningitis (TBM) in adult patients. A total of 22 studies (20 prospective and two retrospective data) have been included in this meta-analysis, having 1927 participants. We perceived acceptable pooled sensitivity, specificity, summary receiver operating characteristics (SROCs), and diagnostic odds ratio (DOR) of 0.85 (95% CI: 0.77-0.90), 0.90 (95% CI: 0.85-0.93), 0.94 (95% CI: 0.91-0.96) and 48 (95% CI: 26-86), respectively, for CSF-ADA for differentiating TBM from non-TBM in adult patients. To ascertain the certainty of evidence for CSF-ADA as a diagnostic marker for TBM, Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) analysis was used. CSF-ADA is an auspicious diagnostic test with a high degree of specificity and acceptable sensitivity for the diagnosis of tuberculous meningitis, however, with very low certainty of evidence.

17.
Infect Chemother ; 55(2): 264-277, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37407244

RESUMO

BACKGROUND: Tuberculous peritonitis is difficult to diagnose due to its non-specific clinical manifestations and lack of proper diagnostic modalities. Current meta-analysis was performed to find the overall diagnostic accuracy of adenosine deaminase (ADA) in diagnosing tuberculous peritonitis. MATERIALS AND METHODS: PubMed, Google Scholar, and Cochrane library were searched to retrieve the published studies which assessed the role of ascitic fluid ADA in diagnosing tuberculous peritonitis from Jan 1980 to June 2022. This meta-analysis included 20 studies and 2,291 participants after fulfilling the inclusion criteria. RESULTS: The pooled sensitivity was 0.90 (95% confidence interval [CI]: 0.85 - 0.94) and pooled specificity was 0.94 (95% CI: 0.92 - 0.95). The positive likelihood ratio was 15.20 (95% CI: 11.70 - 19.80), negative likelihood ratio was 0.10 (95% CI: 0.07 - 0.16) and diagnostic odds ratio was 149 (95% CI: 86 - 255). The area under the summary receiver operating characteristic curve was 0.97. Cut- off value and sample size were found to be the sources of heterogeneity in the mete-regression analysis. CONCLUSION: Ascitic fluid ADA is a useful test for the diagnosis of tuberculous peritonitis with good sensitivity and specificity however, with very low certainty of evidence evaluated by Grading of Recommendations, Assessment, Development and Evaluation approach. Further well- designed studies are needed to validate the diagnostic accuracy of ascitic fluid ADA for tuberculous peritonitis.

18.
Front Public Health ; 11: 1122715, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37143990

RESUMO

Background: The World Health Organization declared the coronavirus disease 2019 (COVID-19) a global pandemic on 11 March 2020. Identifying the infected people and isolating them was the only measure that was available to control the viral spread, as there were no standardized treatment interventions available. Various public health measures, including vaccination, have been implemented to control the spread of the virus worldwide. India, being a densely populated country, required laboratories in different zones of the country with the capacity to test a large number of samples and report test results at the earliest. The Indian Council of Medical Research (ICMR) took the lead role in developing policies, generating advisories, formulating guidelines, and establishing and approving testing centers for COVID-19 testing. With advisories of ICMR, the National Institute of Cancer Prevention and Research (NICPR) established a high-throughput viral diagnostic laboratory (HTVDL) for RT-PCR-based diagnosis of SARS-CoV-2 in April 2020. HTVDL was established during the first lockdown to serve the nation in developing and adopting rapid testing procedures and to expand the testing capacity using "Real-Time PCR." The HTVDL provided its testing support to the national capital territory of Delhi and western Uttar Pradesh, with a testing capacity of 6000 tests per day. The experience of establishing a high-throughput laboratory with all standard operating procedures against varied challenges in a developing country such as India is explained in the current manuscript which will be useful globally to enhance the knowledge on establishing an HTVDL in pandemic or non-pandemic times.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , Teste para COVID-19 , Laboratórios , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Controle de Doenças Transmissíveis
19.
Mol Med Rep ; 27(6)2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37144477

RESUMO

Sudden viral outbreaks have increased in the early part of the 21st century, such as those of severe acute respiratory syndrome coronavirus (SARS­CoV), Middle East respiratory syndrome corona virus, and SARS­CoV­2, owing to increased human access to wildlife habitats. Therefore, the likelihood of zoonotic transmission of human­associated viruses has increased. The emergence of severe acute respiratory syndrome coronavirus 2 in China and its spread worldwide within months have highlighted the need to be ready with advanced diagnostic and antiviral approaches to treat newly emerging diseases with minimal harm to human health. The gold­standard molecular diagnostic approaches currently used are time­consuming, require trained personnel and sophisticated equipment, and therefore cannot be used as point­of­care devices for widespread monitoring and surveillance. Clustered regularly interspaced short palindromic repeats (CRISPR)­associated (Cas) systems are widespread and have been reported in bacteria, archaea and bacteriophages. CRISPR­Cas systems are organized into CRISPR arrays and adjacent Cas proteins. The detection and in­depth biochemical characterization of class 2 type V and VI CRISPR­Cas systems and orthologous proteins such as Cas12 and Cas13 have led to the development of CRISPR­based diagnostic approaches, which have been used to detect viral diseases and distinguish between serotypes and subtypes. CRISPR­based diagnostic approaches detect human single nucleotide polymorphisms in samples from patients with cancer and are used as antiviral agents to detect and destroy viruses that contain RNA as a genome. CRISPR­based diagnostic approaches are likely to improve disease detection methods in the 21st century owing to their ease of development, low cost, reduced turnaround time, multiplexing and ease of deployment. The present review discusses the biochemical properties of Cas12 and Cas13 orthologs in viral disease detection and other applications. The present review expands the scope of CRISPR­based diagnostic approaches to detect diseases and fight viruses as antivirals.


Assuntos
COVID-19 , Humanos , SARS-CoV-2/genética , Sistemas CRISPR-Cas/genética , Pandemias , Bactérias/genética , Teste para COVID-19
20.
Curr Pharm Biotechnol ; 24(10): 1297-1306, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37254276

RESUMO

BACKGROUND: In recent years, the delivery of drugs by nanocomposites has emerged as an exciting field of research for bio-imaging tools and targeted cancer treatment. The large surface area and porous volume of mesoporous silica nanocomposites (MSN's) have gained a lot of interest for their application in the delivery of drugs and the magnetic properties of iron oxide (IO) nanocomposites play a key role in the targeted delivery system. METHODS: In this study, mesoporous silica encapsulated IO nanocomposites loaded with doxorubicin (DOX) were synthesized for the magnetically guided delivery of anticancer drugs. The synthesis of IO nanocomposites was done through the precipitation method, and then silica encapsulation and drug loading were done by the StÖber method. RESULTS: The magnetically driven delivery of the drug is produced by the encapsulation of magnetically active IO in the mesoporous silica shell. The controlled release of DOX is possible because of the MSN's. TEM images show that the nanocomposites have a spherical morphology and average diameter in the range of 120 nm. Power-XRD data confirm the crystalline nature of nanocomposites. The strong absorption peak was observed in UV-Visible spectroscopy at 490 nm and quenching in fluorescence spectra confirms the encapsulation of DOX in the mesoporous silica shell. VSM data showed the magnetic nature of nanocomposites, with large magnetic susceptibility (74.88 emu/g). The use of DOX/IO@Silica nanocomposites as a sustainable drug release and targeted drug delivery vehicle has been reported here. The pH dependent release of DOX was studied and significant release was observed at lower pH. In-vitro cell viability assay and fluorescence imaging assay have demonstrated that these nanocomposites show significant dose-dependent toxicity to cancer cells in the presence of a magnetic field. CONCLUSION: In-vitro studies via the MTT assay showed that these synthesized nanocomposites in culture are non-toxic to healthy cells compared to DOX-induced cytotoxicity due its controlled release and can be further strengthened by magnetic guidance. Therefore, due to its optical properties and potential for guided delivery of drug to the targeted site, these nanocomposites are ideal as an anticancer agent and bio-imaging prob.


Assuntos
Antineoplásicos , Nanocompostos , Nanopartículas , Preparações de Ação Retardada , Dióxido de Silício/química , Sistemas de Liberação de Medicamentos , Doxorrubicina/farmacologia , Antineoplásicos/uso terapêutico , Nanocompostos/química , Ferro , Liberação Controlada de Fármacos , Porosidade , Nanopartículas/química
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