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1.
Crit Rev Immunol ; 41(1): 23-40, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33822523

RESUMO

Genetically engineered T-cell therapies have the adeptness to modernize and revolutionize the treatment of cancer. Cancer immunotherapy, by depending on this fundamental recognition method, supports the antitumor viability of T cells and extends adaptive immunity by encouraging adoptive transfer of genetically engineered T cells. T cells assume a key part in cell-mediated immunity as well as to make strategies for genetically modify T cells, counting chimeric antigen receptor (CAR) T-cell therapy and T-cell receptor (TCR) T-cell therapy. They have accomplished significant advances in the treatment of neoplastic diseases. Tumor cells can produce neoantigens that can possibly be immunogenic, as mutated proteins or proteins with reformed translational processing can be viewed as unfamiliar or foreign by immune system. Recognizable human tumor antigens have prompted a superior understanding the idea of tumor antigens, anti-tumor immune reactions in immunotherapeutic patients as well as tumor escape mechanisms. Furthermore, paucity of exceptionally and homogeneously expressed tumor antigens and intrinsic plasticity of neoplastic cells provide key challenges to specificity, effectiveness, and generally adequacy of genetically engineered T-cell therapies. Difficulties ranges from the determination of antigen targets and managing regulatory and safety issues to effectively explore routes to commercial advancement. In any case, the empowering clinical information, advancement in scientific understanding of tumor immunology along with improvements in manufacture of cell products are altogether propelling the clinical interpretation of modern cancer immunotherapies. In this review, we sum up the advancement of genetically engineered T cells, tumor antigen with intrigue the most recent investigation regarding genetically engineered T cells for cancer immunotherapy, and to confer strategies for refining enactment of these T cells to combat cancers.


Assuntos
Antígenos de Neoplasias , Neoplasias , Antígenos de Neoplasias/genética , Humanos , Imunoterapia , Imunoterapia Adotiva , Neoplasias/terapia , Receptores de Antígenos de Linfócitos T/genética , Linfócitos T
2.
Mol Biol Rep ; 49(3): 2359-2373, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34822068

RESUMO

Beta-hemoglobinopathies exhibit a heterogeneous clinical picture with varying degrees of clinical severity. Pertaining to the limited treatment options available, where blood transfusion still remains the commonest mode of treatment, pharmacological induction of fetal hemoglobin (HbF) has been a lucrative therapeutic intervention. Till now more than 70 different HbF inducers have been identified. The practical usage of many pharmacological drugs has been limited due to safety concerns. Natural compounds, like Resveratrol, Ripamycin and Bergaptene, with limited cytotoxicity and high efficacy have started capturing the attention of researchers. In this review, we have summarized pharmacological drugs and bioactive compounds isolated from natural sources that have been shown to increase HbF significantly. It primarily discusses recently identified synthetic and natural compounds, their mechanism of action, and their suitable screening platforms, including high throughput drug screening technology and biosensors. It also delves into the topic of combinatorial therapy and drug repurposing for HbF induction. Overall, we aim to provide insights into where we stand in HbF induction strategies for treating ß-hemoglobinopathies.


Assuntos
Produtos Biológicos , Hemoglobinopatias , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Hemoglobina Fetal , Hemoglobinopatias/tratamento farmacológico , Humanos
3.
Nano Lett ; 21(1): 673-679, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33337876

RESUMO

Probing structural changes of a molecule induced by charge transfer is important for understanding the physicochemical properties of molecules and developing new electronic devices. Here, we interrogate the structural changes of a single diketopyrrolopyrrole (DPP) molecule induced by charge transport at a high bias using scanning tunneling microscope break junction (STM-BJ) techniques. Specifically, we demonstrate that application of a high bias increases the average nonresonant conductance of single Au-DPP-Au junctions. We infer from the increased conductance that resonant charge transport induces planarization of the molecular backbone. We further show that this conformational planarization is assisted by thermally activated junction reorganization. The planarization only occurs under specific electronic conditions, which we rationalize by ab initio calculations. These results emphasize the need for a comprehensive view of single-molecule junctions which includes both the electronic properties and structure of the molecules and the electrodes when designing electrically driven single-molecule motors.

4.
Curr Psychol ; : 1-10, 2022 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-35136331

RESUMO

The effects of coronavirus are not just physical but also psychological in all age groups and more so common among children. Some children may have had experience of quarantine restrictions during this COVID-19 pandemic. Due to increased digital connections 'emotional contagion' where the distress and fear experienced by one spread to another person may also be common in children. The present study aims to determine whether COVID-19 pandemic and the lockdown has caused stress and affected mental health of children and youth. The current study assessed stress in children and youth between 9 and 18 years age based on Short Self-Rating Questionnaire (SSRQ) during the COVID-19 pandemic. The study design was an observational study,  a descriptive cross-sectional study using online survey. Total 369 schools children participated in the survey. Score Scale and analysis was done to categorize the stress levels as Low, Moderate and Severe. Data analysis based on the total score levels (Delhi+Mathura zone, n=369) showed 30.08% (n=111) students with Low stress level, 62.87% (n=232) within Moderate stress level and 7.08% (n=26) with severe stress level. Students T Test revealed that there was a significant difference (p≤0.04) of the stress level male vs. female in total (Delhi + Mathura zone combined). However, the stress level was not significantly different between Delhi and Mathura zone alone. It is utmost to give primary importance to address the stress issues in children and adoloscents in the current scenario. Inclusion of Intervention strategies that are empirically supported and culturally appropriate as per the need of the communities for children and families may be helpful. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12144-022-02827-3.

5.
Beilstein J Org Chem ; 18: 133-142, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35140814

RESUMO

A heterogeneous and magnetically recyclable Ni-chitosan nanocatalyst was synthesized and thoroughly characterized by powder Fourier-transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) analysis, scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), energy-dispersive X-ray (EDX) spectroscopy, etc. It was effectively utilized in the eco-friendly synthesis of new C5-C6-unsubstituted 1,4-DHPs under ultrasonic irradiation. The important focus of the methodology was to develop an environmentally friendly protocol with a short reaction time and a simple reaction procedure. The other advantages of this protocol are a wide substrate scope, a very good product yield, the use of an eco-friendly solvent and a recyclable nanocatalyst, as well as reaction at room temperature.

6.
Int J Heat Mass Transf ; 135: 44-51, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30880830

RESUMO

Vapor bubble nucleation during subcooled boiling on thin strip wire heaters and the resultant vibrations are studied experimentally. The results show how the subcooled boiling-induced vibrations (SBIV) are intrinsically related to the hydrodynamic flow induced near the heated wires. It is shown that the dominant force responsible for the vibrations in this case is imposed by a localized strong hydrodynamic flow rather than by the vapor recoil force. The dominant frequency of SBIV is the fundamental frequency of the wire, regardless of the individual departure frequencies of the nucleating vapor bubbles. The recorded wire vibrations are used to quantify the hydrodynamic flow. It is shown experimentally and theoretically that the flow fades exponentially with distance from the wire.

7.
J Am Chem Soc ; 140(41): 13167-13170, 2018 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-30280891

RESUMO

We study the single-molecule transport properties of small bandgap diketopyrrolopyrrole oligomers (DPP n, n = 1-4) with lengths varying from 1 to 5 nm. At a low bias voltage, the conductance decays exponentially as a function of length indicative of nonresonant transport. However, at a high bias voltage, we observe a remarkably high conductance close to 10-2 G0 with currents reaching over 0.1 µA across all four oligomers. These unique transport properties, together with density functional theory-based transport calculations, suggest a mechanism of resonant transport across the highly delocalized DPP backbones in the high bias regime. This study thus demonstrates the unique properties of diketopyrrolopyrrole derivatives in achieving highly efficient long-range charge transport in single-molecule devices.

8.
Mol Pharm ; 13(4): 1393-404, 2016 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-26950163

RESUMO

Sustained controlled drug release is one of the prominent contributions for more successful treatment outcomes in the case of several diseases. However, the incorporation of hydrophilic drugs into nanofibers, a promising novel delivery system, and achieving a long-term sustained release still pose a challenging task. In this work we demonstrated a robust method of avoiding burst release of drugs and achieving a sustained drug release from 2 to 4 weeks using core-shell nanofibers with poly(methyl methacrylate) (PMMA) shell and monolithic poly(vinyl alcohol) (PVA) core or a novel type of core-shell nanofibers with blended (PVA and PMMA) core loaded with ciprofloxacin hydrochloride (CIP). It is also shown that, for core-shell nanofibers with monolithic core, drug release can be manipulated by varying flow rate of the core PVA solution, whereas for core-shell nanofibers with blended core, drug release can be manipulated by varying the ratios between PMMA and PVA in the core. During coaxial electrospinning, when the solvent from the core evaporates in concert with the solvent from the shell, the interconnected pores spanning the core and the shell are formed. The release process is found to be desorption-limited and agrees with the two-stage desorption model. Ciprofloxacin-loaded nanofiber mats developed in the present work could be potentially used as local drug delivery systems for treatment of several medical conditions, including periodontal disease and skin, bone, and joint infections.


Assuntos
Ciprofloxacina/química , Sistemas de Liberação de Medicamentos/métodos , Nanofibras/química , Preparações de Ação Retardada , Interações Hidrofóbicas e Hidrofílicas , Espectroscopia de Infravermelho com Transformada de Fourier
9.
Mol Pharm ; 13(1): 295-305, 2016 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-26635214

RESUMO

Nanofibers represent an attractive novel drug delivery system for prolonged and controlled release. However, sustained release of hydrophilic drugs, like ciprofloxacin hydrochloride (CIP), from polymeric nanofibers is not an easy task. The present study investigates the effect of different hydrophobic polymers (PCL and PMMA) alone in monolithic nanofibers or with hydrophilic polymers (PVA, PEO, and chitosan) in blended nanofibers aiming to achieve sustained CIP release. CIP release from PCL nanofibers was 46% and from PMMA just 1.5% over 40 day period. Thus, PMMA holds great promise for modification of CIP release from blended nanofibers. PMMA blends with 10% PEO, PVA, or chitosan were used to electrospin nanofibers from solution in the mixture of acetic and formic acid. These nanofibers exhibited different drug-release profiles: PEO containing nanofiber mats demonstrated high burst effect, chitosan containing mats revealed very slow gradual release, and PVA containing mats yielded smaller burst effect with favorable sustained release. We have also shown that gradual sustain release of antibiotic like CIP can be additionally tuned over 18 days with various blend ratios of PMMA with PVA or chitosan reaching almost 100%. A mathematical model in agreement with the experimental observation revealed that the sustained CIP release from the blended nanofibers corresponded to the two-stage desorption process.


Assuntos
Ciprofloxacina/química , Nanofibras/química , Polímeros/química , Polimetil Metacrilato/química , Interações Hidrofóbicas e Hidrofílicas
10.
Recent Pat Biotechnol ; 18(3): 210-226, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37779409

RESUMO

The COVID-19 pandemic is to escalate globally and acquire new mutations quickly, so accurate diagnostic technologies play a vital role in controlling and understanding the epidemiology of the disease. A plethora of technologies acquires diagnosis of individuals and informs clinical management of COVID. Some important biochemical parameters for COVID diagnosis are the elevation of liver enzymes, creatinine, and nonspecific inflammatory markers such as C-reactive protein (CRP) and Interleukin 6 (IL-6). The main progression predictors are lymphopenia, elevated D-dimer, and hyperferritinemia, although it is also necessary to consider LDH, CPK, and troponin in the marker panel of diagnosis. Owing to the greater sensitivity and accuracy, molecular technologies such as conventional polymerase chain reaction (PCR), reverse transcription (RT)-PCR, nested PCR, loop-mediated isothermal amplification (LAMP), and xMAP technology have been extensively used for COVID diagnosis for some time now. To make so many diagnostics accessible to general people, many techniques may be exploited, including point of care (POC), also called bedside testing, which is developing as a portable promising tool in pathogen identification. Some other lateral flow assay (LFA)-centered techniques like SHERLOCK, CRISPR-Cas12a (AIOD-CRISPR), and FNCAS9 editor limited uniform detection assay (FELUDA), etc. have shown auspicious results in the rapid detection of pathogens. More recently, low-cost sequencing and advancements in big data management have resulted in a slow but steady rise of next-generation sequencing (NGS)-based approaches for diagnosis that have potential relevance for clinical purposes and may pave the way toward a better future. Due to the COVID-19 pandemic, various institutions provided free, specialized websites and tools to promote research and access to critically needed advanced solutions by alleviating research and analysis of data within a substantial body of scientific and patent literature regarding biochemical and molecular diagnosis published since January 2020. This circumstance is unquestionably unique and difficult for anyone using patent information to find pertinent disclosures at a specific date in a trustworthy manner.


Assuntos
COVID-19 , Humanos , COVID-19/diagnóstico , SARS-CoV-2/genética , Pandemias , Patentes como Assunto , Sensibilidade e Especificidade , Teste para COVID-19
11.
Artigo em Inglês | MEDLINE | ID: mdl-38409721

RESUMO

Alternations in protein ubiquitination along with hypoxia-inducible factor (HIF) signaling contribute to tumorigenesis and breast tumor advancement. Ubiquitination is an impulsive process, which is coordinately governed by E3 ligases and deubiquitinases (DUBs), that have come out as charismatic therapeutic targets. HIF expression, as well as the transcriptional process in malignancies, are frequently elevated, resulting in pitiable clinical outcomes. According to increasing research, multiple E3 ligases, in addition to UBDs work together to modulate HIF expression and activity, permitting breast cancer cells to make out a hypoxic milieu. On the other hand, hypoxia and HIF signaling regulate numerous E3 ligases as well as DUBs. Interpreting involved networks connecting E3 ligase, DUBS, and HIF will reveal profound mechanisms of physiological response to hypoxia and aid in the discovery of new molecular references for cancer management. The present state of knowledge about the entire kinship among E3 ligase, DUBs, and HIF signaling is reviewed here, emphasizing using E3 ligase or DUB inhibitors in breast cancer.

12.
Clin Chim Acta ; 557: 117855, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38453050

RESUMO

Breast cancer is the most common cancer and the leading cause of mortality worldwide. Despite advancements in detection and treatment, it remains a major cause of cancer-related deaths in women. Breast cancer stem cells (BCSCs) are a crucial group of cells responsible for carcinogenesis, metastasis, medication resistance, and tumor recurrence. Identifying and understanding their molecular pathways is essential for developing effective breast cancer therapy. BCSCs are responsible for tumor genesis, development, metastasis, treatment resistance, and recurrence. Biomarkers are essential tools for identifying high-risk patients, improving diagnostic accuracy, developing follow-up programs, assessing treatment susceptibility, and predicting prognostic outcomes. Stem cell intervention therapy can provide specialized tools for precision therapy. Biomarker analysis in cancer patients is crucial to identify cells associated with disease progression and post-therapeutic relapse. However, negative post-therapeutic impacts can enhance cancer stemness by boosting BCSCs plasticity phenotypes, activating stemness pathways in non-BCSCs, and promoting senescence escape, leading to tumor relapse and metastasis. Despite the advancements in precision medicine, challenges persist in identifying stem cell markers, limiting the number of eligible patients for treatment. The diversity of biomedical research hinders the development of individualization-based preventative, monitoring, and treatment strategies, especially in oncology. Integrating and interpreting clinical and scientific data remains challenging. The development of stem cell-related indicators could significantly improve disease precision, enabling stem cell-targeted therapy and personalized treatment plans, although BCSCs are promising for breast cancer treatment optimization, serving as biomarkers for current therapy modalities. This summary discusses recent advancements in breast cancer stem cell research, including biomarkers, identification methods, molecular mechanisms, and tools for studying their biological origin and lineage development for precision medicine.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Recidiva Local de Neoplasia , Biomarcadores/metabolismo , Células-Tronco Neoplásicas/patologia , Recidiva , Biomarcadores Tumorais/metabolismo
13.
J Egypt Natl Canc Inst ; 36(1): 7, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38462581

RESUMO

The progression of metastasis, a complex systemic disease, is facilitated by interactions between tumor cells and their isolated microenvironments. Over the past few decades, researchers have investigated the metastatic spread of cancer extensively, identifying multiple stages in the process, such as intravasation, extravasation, tumor latency, and the development of micrometastasis and macrometastasis. The premetastatic niche is established in target organs by the accumulation of aberrant immune cells and extracellular matrix proteins. The "seed and soil" idea, which has become widely known and accepted, is being used to this day to guide cancer studies. Changes in the local and systemic immune systems have a major impact on whether an infection spreads or not. The belief that the immune response may play a role in slowing tumor growth and may be beneficial against the metastatic disease underpins the responsiveness shown in the immunological landscape of metastasis. Various hypotheses on the phylogenesis of metastases have been proposed in the past. The primary tumor's secreting factors shape the intratumoral microenvironment and the immune landscape, allowing this progress to be made. Therefore, it is evident that among disseminated tumor cells, there are distinct phenotypes that either carry budding for metastasis or have the ability to obtain this potential or in systemic priming through contact with substantial metastatic niches that have implications for medicinal chemistry. Concurrent immunity signals that the main tumor induces an immune response that may not be strong enough to eradicate the tumor. Immunotherapy's success with some cancer patients shows that it is possible to effectively destroy even advanced-stage tumors by modifying the microenvironment and tumor-immune cell interactions. This review focuses on the metastasome in colorectal carcinoma and the therapeutic implications of site-specific metastasis, systemic priming, tumor spread, and the relationship between the immune system and metastasis.


Assuntos
Neoplasias Colorretais , Humanos , Neoplasias Colorretais/terapia , Neoplasias Colorretais/patologia , Metástase Neoplásica , Microambiente Tumoral
14.
Curr Mol Med ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38766832

RESUMO

Hypoxia, characterized by insufficient oxygen supply to tissues, is a significant factor in tumor growth and resistance to treatment. The hypoxia-inducible factor (HIF) signaling pathway is activated when oxygen levels decline, influencing cell activities and promoting tumor progression. HIF-1α and HIF-2α are the main targets for therapeutic intervention in tumors. Nevertheless, the significance of HIF-2α is often overlooked. This review examines the physiological role of HIF-2α in tumor growth and its involvement in tumor growth. HIFs, composed of hypoxia-responsive α and oxygeninsensitive ß subunits, play a crucial role in controlling gene expression in both normal and solid tumor tissues under low oxygen levels. HIF-3α, formerly considered a detrimental modulator of HIF-regulated genes, exerts a transcriptional regulatory role by inhibiting gene expression through competition with HIF-1α and HIF-2α for binding to transcriptional sites in target genes under hypoxia. Recent research indicates that various HIF-3 variants exhibit distinct and potentially contrasting functionalities. Hypoxia often occurs during the initiation and progression of cancer formation. Recent research has discovered that HIF-2α, also known as endothelial PAS domain protein 1, has a significant impact on tumors. HIF-2α is a significant cancer-causing gene and a crucial predictor of prognosis in non-small cell lung cancer. However, due to limited research investigating the relationship between HIF-2α and small-cell lung cancer, it is not possible to reach a definitive conclusion. HIF-2α plays a vital function in cancer by preserving the stemness of cancer cells. This review provides a comprehensive overview of HIF-2 and the role of HIF-3 in various cancer-related processes, as well as its potential as a targeted therapeutic approach.

15.
Artigo em Inglês | MEDLINE | ID: mdl-38939989

RESUMO

COVID-19 pandemic is casting a long shadow, and the appearance of the JN.1 variety calls attention to the necessity of maintaining heightened awareness. It considers the strength that has been developed via immunization programs and the necessity of global collaboration to find a solution in light of the emergence of new strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Phylogenetically, the SARS-CoV-2 Omicron XBB lineages, which include EG.5.1 and HK.3, are different from the SARS-CoV-2 BA.2.86 lineage, which was initially discovered in August 2023. More than 30 mutations in the spike (S) protein are carried by BA.2.86 compared to XBB and BA.2, suggesting a high potential for immune evasion. JN.1 (BA.2.86.1.1), a descendant of BA.2.86, appeared in late 2023 after the format had undergone evolution. JN.1 carries three mutations in proteins that do not include S, as well as S:L455S. As previously demonstrated, the HK.3 and other "FLip" variations possess the S:L455F mutation, which enhances transmissibility and immune escape capacity in comparison to the parental EG.5.1 variety. This mutation is a characteristic of JN.1. The COVID-19 virus is dynamic and evolves over time. New varieties can sometimes spread more quickly or effectively after these alterations. If that happens, the new variant has a chance to outpace the current varieties in terms of frequency.

16.
Anticancer Agents Med Chem ; 24(10): 729-732, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38415470

RESUMO

A small therapeutic range of oxygen is required for effective metabolism. As a result, hypoxia (low oxygen concentration) is one of the most potent inducers of gene expression, metabolic alterations, and regenerative processes, such as angiogenesis, stem cell proliferation, migration, and differentiation. The cellular response is controlled by sensing the increased oxygen levels (hyperoxia) or hypoxia via specific chemoreceptor cells. Surprisingly, changes in free oxygen concentration instead of absolute oxygen levels may be regarded as a deficiency of oxygen at the cellular level. Recurrent intermittent hyperoxia may trigger many mediators of cellular pathways typically generated during hypoxia. The dilemma of hyperoxic-hypoxic conditions is known as the hyperoxic-hypoxic paradox. According to the latest data, the hypoxic microenvironment, crucial during cancer formation, has been demonstrated to play a key role in regulating breast cancer growth and metastasis. Hypoxic circumstances cause breast cancer cells to respond in a variety of ways. Transcription factors are identified as hypoxia-inducible factors (HIFs) that have been suggested to be a factor in the pathobiology of breast cancer and a possible therapeutic target, driving the cellular response to hypoxia. Breast cancer has a dismal prognosis due to a high level of resistance to practically all well-known cancer management that has been related to hypoxia-based interactions between tumor cells and the stromal milieu. We attempt to review the enigma by exploring the starring roles of HIFs in breast cancer, the HIF paradox, and the hyperoxic-hypoxic enigma.


Assuntos
Neoplasias da Mama , Microambiente Tumoral , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/tratamento farmacológico , Feminino , Oxigênio/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Animais
17.
Infect Disord Drug Targets ; 24(6): e220124225916, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38258765

RESUMO

Coronavirus Disease-19 (COVID-19) is an infectious disease brought on by the extremely pathogenic and contagious severe acute respiratory syndrome-virus-2 (SARS-CoV-2). The agenda for the COVID-19 pandemic is dynamic and includes recent developments. Seven variants under monitoring (VUMs), one variant of interest (VOI), XBB.1.5, and their offspring lineages are currently being actively monitored by WHO. The VUMs are BA.2.75, CH.1.1, BQ.1, XBB (with the exception of XBB.1.5, XBB.1.16, and XBB.1.9.1), XBF, and XBB.1.16. With 95 countries having reported finding XBB.1.5 (VOI), it is still the most common strain worldwide, responsible for 47.9% of cases from epidemiological January to March 2023. Seventy nations discovered XBB.1.5 in February and March 2023 and posted sequencing data to GISAID. Of the 43 nations that uploaded more than 50 sequences, XBB.1.5 prevalence has increased to more than 50% in 11 nations. Over 23000 deaths and 3 million new cases were recorded globally in March and April 2023. Worldwide detection of a new COVID-19 strain has prompted specialists to issue a warning that the virus is "circulating unchecked". The Greek goddess of conflict and discord Eris has inspired the nicknaming of EG 5.1, a subvariant of Omicron. The strain is becoming more prevalent in the USA and cases are increasing in the UK. The severity of each SARS-CoV- 2 variant has been comparable, although a more severe form might develop. Eris is an ancestor of Omicron and exhibits some of its characteristics. Reinfection risk can be influenced by a variety of variables, including age, location, and health equity and the COVID-19 vaccine is more or less effective depending on the strain.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , COVID-19/virologia , SARS-CoV-2/genética
18.
Curr Mol Med ; 24(2): 205-216, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-36892117

RESUMO

Redox homeostasis is essential for keeping our bodies healthy, but it also helps breast cancer cells grow, stay alive, and resist treatment. Changes in the redox balance and problems with redox signaling can make breast cancer cells grow and spread and make them resistant to chemotherapy and radiation therapy. Reactive oxygen species/reactive nitrogen species (ROS/RNS) generation and the oxidant defense system are out of equilibrium, which causes oxidative stress. Many studies have shown that oxidative stress can affect the start and spread of cancer by interfering with redox (reduction-oxidation) signaling and damaging molecules. The oxidation of invariant cysteine residues in FNIP1 is reversed by reductive stress, which is brought on by protracted antioxidant signaling or mitochondrial inactivity. This permits CUL2FEM1B to recognize its intended target. After the proteasome breaks down FNIP1, mitochondrial function is restored to keep redox balance and cell integrity. Reductive stress is caused by unchecked amplification of antioxidant signaling, and changes in metabolic pathways are a big part of breast tumors' growth. Also, redox reactions make pathways like PI3K, PKC, and protein kinases of the MAPK cascade work better. Kinases and phosphatases control the phosphorylation status of transcription factors like APE1/Ref-1, HIF-1, AP-1, Nrf2, NF-B, p53, FOXO, STAT, and - catenin. Also, how well anti-breast cancer drugs, especially those that cause cytotoxicity by making ROS, treat patients depends on how well the elements that support a cell's redox environment work together. Even though chemotherapy aims to kill cancer cells, which it does by making ROS, this can lead to drug resistance in the long run. The development of novel therapeutic approaches for treating breast cancer will be facilitated by a better understanding of the reductive stress and metabolic pathways in tumor microenvironments.


Assuntos
Antioxidantes , Neoplasias da Mama , Humanos , Feminino , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Oxirredução , Estresse Oxidativo , Resistência a Medicamentos , Microambiente Tumoral
19.
J Indian Soc Periodontol ; 28(1): 122-128, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38988957

RESUMO

Background: Periodontitis is a multifactorial, polymicrobial oral inflammatory illness brought on by oral pathogens. Porphyromonas gingivalis is a Gram-negative, obligatory anaerobic, black-pigmented coccobacillus and is regarded as a primary etiological factor in the progression of periodontitis. Rapid, highly senstitive and specific detection methods are emerging. The present study aimed to evaluate the loop-mediated isothermal amplification (LAMP) technique for efficiently detecting P. gingivalis from subgingival plaque samples of chronic periodontitis patients. Materials and Methods: This study included 50 subgingival plaque samples from patients suffering from chronic periodontitis. The DNA (Deoxyribonucleic acid) was extracted by the "modified proteinase K" method. A set of six primers, targeting the pepO gene of P. gingivalis, was used for conducting LAMP. The amplification was visualized by naked-eye detection and agarose electrophoresis. Conventional polymerase chain reaction (PCR) and real-time qantitative PCR (qPCR) were carried out by targeting the 16SrRNA (16S ribosomal ribonucleic acid) gene of P. gingivalis. Results: The results showed that LAMP detected P. gingivalis in 40 out of 50 samples (80%). Whereas, qPCR and conventional PCR technique detected P. gingivalis in 38 (76%) and 33 (66%) samples respectively. The sensitivity and specificity of the LAMP method were 94.87% and 90.90%, respectively. With qPCR, the sensitivity and specificity were found to be 92.30% and 81.81%, respectively, whereas, with conventional PCR, it was found to be 76.92% and 72.72%, respectively. Conclusion: LAMP is an efficient technique for quick, accurate, and reliable identification of P. gingivalis from subgingival plaque samples. The technique needs to be validated analytically, and further studies can be conducted by taking saliva and/or gingival crevicular fluid samples from periodontitis patients.

20.
Cureus ; 16(2): e53684, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38455790

RESUMO

Background Internship is the time period when young doctors learn to balance between professional and personal lives. If they have good awareness and practice of any kind of physical activity during this period, it will help them to continue it forward. This enables them to educate and inspire people and patients around them. The main objectives of this study were to assess patterns of physical activity among medical interns and to understand the factors preventing physical activity among them. Methodology This cross-sectional survey was carried out among interns of a tertiary care hospital in western Maharashtra from July 2022 to September 2022. Ethical clearance was obtained before starting data collection. The survey was administered to those who fulfilled the inclusion criteria. The questionnaire was adopted from the Global Physical Activity Questionnaire. The data collected were entered into Microsoft Excel (Microsoft Corporation, Redmond, WA) and analysis was done using MedCalc v.18.2.1 (MedCalc Software Ltd, Ostend, Belgium). Results A total of 220 interns were enrolled in the survey, of which 13 were removed due to incomplete data and 28 interns did not participate in the study. Finally, 179 interns were included for analysis in the study. The response rate was 87.27%. The mean age of participants was 23.12 years. The study population consisted of 72 (40.22%) males and 107 (59.78%) females. Among participants, 33 interns (18.44%) were involved in vigorous activity during work, and 108 interns (60.34%) were involved in moderate physical activity during work. The median time of a sedentary lifestyle was 300 minutes per day and was more common among males. Cumulatively busy working schedules and exam preparation were the important reasons for reduced physical activity. Conclusion There is a gap in the practice of physical activity among interns. A sedentary lifestyle was more prevalent among male interns than in female interns. The main constraints were demanding working hours and the pressure of competitive exams. Medical students will become doctors in the future who can advise their patients on healthy lifestyle habits. We recommend that it is necessary to promote physical activity in medical schools and to reinforce the importance of physical exercise in the medical curriculum.

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