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The HbD Punjab trait is a less common hemoglobin variant in the Saurashtra region of Gujarat. This patient presented to the General Medicine and Biochemistry Department at All India Institute of Medical Sciences, Rajkot, Hospital, for the HbA1c analysis by high-performance liquid chromatography (HPLC). The patient was 52 years old, a known case of type 2 diabetes mellitus and hypertension, and presented with complaints of generalized malaise and fatigability for the previous ten to twelve months. On physical examination, there was no evidence of pallor, lymphadenopathy, splenomegaly, or hepatomegaly. Peripheral blood smear revealed normocytic normochromic RBC, and platelets were adequate and normal in morphology. The HPLC analysis revealed heterozygous for hemoglobin D (HbD Punjab trait), and false high HbA1c corresponds to fasting plasma glucose (FPG) levels due to abnormal separation. However, genetic counseling is highly recommended to detect any potential reproductive risk factors.
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This randomised, crossover, sham-controlled study explored the neural basis of source-monitoring, a crucial cognitive process implicated in schizophrenia. Left superior temporal gyrus (STG) and dorsolateral prefrontal cortex (DLPFC) were the key focus areas. Thirty participants without neurological or psychological disorders underwent offline sham and active tDCS sessions with specific electrode montage targeting the left STG and DLPFC. Source-monitoring tasks, reality monitoring (Hear-Imagine), internal source-monitoring (Say-Imagine), and external source monitoring (Virtual-Real) were administered. Paired t-test and estimation statistics was performed with Graphpad version 10.1.0. The Benjamini-Hochberg procedure was employed to control the false discovery rate in multiple hypothesis testing. A significant improvement in internal source monitoring tasks (p = 0.001, Cohen's d = 0.97) was observed, but reality monitoring tasks demonstrated moderate improvement (p = 0.02, Cohen's d = 0.44). The study provides insights into the neural mechanisms of source monitoring in healthy individuals and proposes tDCS as a therapeutic intervention, laying the foundation for future studies to refine tDCS protocols and develop individualized approaches to address source monitoring deficits in schizophrenia.
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Estudos Cross-Over , Alucinações , Esquizofrenia , Estimulação Transcraniana por Corrente Contínua , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Masculino , Feminino , Alucinações/terapia , Alucinações/fisiopatologia , Adulto , Esquizofrenia/terapia , Esquizofrenia/fisiopatologia , Adulto Jovem , Córtex Pré-Frontal Dorsolateral/fisiologia , Lobo Temporal/fisiopatologia , Lobo Temporal/fisiologiaRESUMO
Nanomaterials with enzyme-like properties are known as 'nanozymes'. Nanozymes are preferred over natural enzymes due to their nanoscale characteristics and ease of tailoring of their physicochemical properties such as size, structure, composition, surface chemistry, crystal planes, oxygen vacancy, and surface valence state. Interestingly, nanozymes can be precisely controlled to improve their catalytic ability, stability, and specificity which is unattainable by natural enzymes. Therefore, tailor-made nanozymes are being favored over natural enzymes for a range of potential applications and better prospects. In this context, metal oxide nanoparticles with nanozyme-mimicking characteristics are exclusively being used in biomedical sectors and opening new avenues for future nanomedicine. Realising the importance of this emerging area, here, we discuss the mechanistic actions of metal oxide nanozymes along with their key characteristics which affect their enzymatic actions. Further, in this critical review, the recent progress towards the development of point-of-care (POC) diagnostic devices, cancer therapy, drug delivery, advanced antimicrobials/antibiofilm, dental caries, neurodegenerative diseases, and wound healing potential of metal oxide nanozymes is deliberated. The advantages of employing metal oxide nanozymes, their potential limitations in terms of nanotoxicity, and possible prospects for biomedical applications are also discussed with future recommendations.
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Doxorubicin (DOX) is an important drug for cancer treatment, but its clinical application is limited due to its toxicity and side effects. Therefore, detecting the concentration of DOX during treatment is crucial for enhancing efficacy and reducing side effects. In this study, the authors developed a biophotonic fiber sensor based on localized surface plasmon resonance (LSPR) with the multimode fiber (MMF)-four core fiber (FCF)-seven core fiber (SCF)-MMF-based direct-taper and anti-taper structures for the specific detection of DOX. Compared to other detection methods, it has the advantages of high sensitivity, low cost, and strong anti-interference ability. In this experiment, multi-walled carbon nanotubes (MWCNTs), cerium-oxide nanorods (CeO2-NRs), and gold nanoparticles (AuNPs) were immobilized on the probe surface to enhance the sensor's biocompatibility. MWCNTs and CeO2-NRs provided more binding sites for the fixation of AuNPs. By immobilizing AuNPs on the surface, the LSPR was stimulated by the evanescent field to detect DOX. The sensor surface was functionalized with DOX aptamers for specific detection, enhancing its specificity. The experiments demonstrated that within a linear detection range of 0-10 µM, the sensitivity of the sensor is 0.77 nm/µM, and the limit of detection (LoD) is 0.42 µM. Additionally, the probe's repeatability, reproducibility, stability, and selectivity were evaluated, indicating that the probe has high potential for detecting DOX during cancer treatment.
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Doxorrubicina , Ouro , Nanopartículas Metálicas , Ressonância de Plasmônio de Superfície , Doxorrubicina/farmacologia , Humanos , Ressonância de Plasmônio de Superfície/instrumentação , Ouro/química , Nanopartículas Metálicas/química , Neoplasias/tratamento farmacológico , Nanotubos de Carbono/química , Técnicas Biossensoriais/instrumentação , Fibras Ópticas , Desenho de Equipamento , Antibióticos Antineoplásicos/análise , Cério/química , Tecnologia de Fibra Óptica/instrumentaçãoRESUMO
The synthesis and characterization of chitosan encapsulated copper oxide nanocomposites (CuNPs) using plant extracts for the photocatalytic degradation of second-generation antibiotics, cefixime and cefuroxime, were investigated. The study revealed that the presence of diverse chemical components in the plant extract significantly influenced the size of the CuNPs, with transmission electron microscopy (TEM) showing spherical shapes and sizes ranging from 11-35 nm. The encapsulation process was confirmed by an increase in size for certain samples, indicating successful encapsulation. X-ray photoelectron spectroscopy (XPS) analysis further elucidated the chemical makeup, confirming the valency state of Cu2+ and the presence of Cu-O bonding, with no contaminants detected. Photocatalytic activity assessments demonstrated that the copper oxide nanocomposites exhibited significant degradation capabilities against both antibiotics under UV light irradiation, with encapsulated nanocomposites (EnCu30) showing up to 96.18% degradation of cefuroxime within 60 min. The study highlighted the influence of chitosan encapsulation on enhancing photocatalytic performance, attributed to its high adsorption capability. Recycling studies confirmed the sustainability of the Cu nanocomposites, maintaining over 89% degradation rate after five consecutive cycles. This research underscores the potential of green-synthesized CuNPs as efficient, stable photocatalysts for the degradation of harmful antibiotics, contributing to environmental sustainability and public health protection.
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Antibacterianos , Quitosana , Cobre , Nanocompostos , Poluentes Químicos da Água , Quitosana/química , Nanocompostos/química , Cobre/química , Antibacterianos/química , Poluentes Químicos da Água/química , Cefalosporinas/química , Química VerdeRESUMO
BACKGROUND: Crisaborole (CB), a boron-based compound, is the first topical PDE4 inhibitor to be approved by the US Food and Drug Administration (2016) for the treatment of Atopic Dermatitis. It is marketed as a 2% ointment (Eucrisa, Pfizer). However, CB is insoluble in water; therfore, CB glycersomes were formulated to enhance its permeation flux across the skin. OBJECTIVE: We developed a glycerosomal gel of CB and compared its in vitro release and permeation flux with the 2% conventional ointment. METHODS: Glycerosomes were prepared using a thin film hydration method employing CB, soya phosphatidylcholine, and cholesterol. The formed film was further hydrated employing a mixture of phosphate buffer pH 7.4 /glycerin solution containing varying percentages (20,30, 40, and 50 %) of glycerol. The glycerosomes obtained were characterized by their size, polydispersity index (PDI), and Zeta potential. The entrapment efficiency of the optimized formulation (F 1) was determined. The in vitro release of F1 was compared with its 2% conventional ointment. F1 was further incorporated into carbopol 934 P gel. The gel was characterized by pH, viscosity, spreadability, and drug content. The permeability flux of the glycerosomal gel was compared with its 2% conventional ointment. RESULTS: The optimized CB glycerosomes had a vesicle size of 137.5 ± 50.58 nm, PDI 0.342, and zeta potential -65.4 ± 6.75 mV. CB glycerosomal gel demonstrated a 2.13-fold enhancement in the permeation flux. CONCLUSION: It can thereby be concluded that glycerosomes can be an effective delivery system to enhance the penetration of CB across the skin.
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Cancer treatment is challenged due to immunosuppressive inflammatory tumour microenvironment (TME) caused by infiltration of tumour-promoting and inhibition of tumour-inhibiting immune cells. Here, we report the engineering of chimeric nanomicelles (NMs) targeting the cell proliferation using docetaxel (DTX) and inflammation using dexamethasone (DEX) that alters the immunosuppressive TME. We show that a combination of phospholipid-DTX conjugate and PEGylated-lipid-DEX conjugate can self-assemble to form sub-100 nm chimeric NMs (DTX-DEX NMs). Anti-cancer activities against syngeneic and xenograft mouse models showed that the DTX-DEX NMs are more effective in tumour regression, enhance the survival of mice over other treatment modes, and alter the tumour stroma. DTX-DEX NMs cause a significant reduction in myeloid-derived suppressor cells, alter the polarization of macrophages, and enhance the accumulation of cytotoxic CD4+ and CD8+ T cells in tumour tissues, along with alterations in cytokine expression. We further demonstrated that these DTX-DEX NMs inhibit the synthesis of prostaglandins, especially PGE2, by targeting the cyclooxygenase 2 that is partly responsible for immunosuppressive TME. Therefore, this study presents, for the first time, the engineering of lithocholic acid-derived chimeric NMs that affect the prostaglandin pathway, alter the TME, and mitigate tumour progression with enhanced mice survival.
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Antineoplásicos , Prostaglandinas , Humanos , Camundongos , Animais , Prostaglandinas/farmacologia , Linfócitos T CD8-Positivos , Docetaxel/uso terapêutico , Docetaxel/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Terapia de Imunossupressão , Microambiente Tumoral , Linhagem Celular TumoralRESUMO
Background Maternal obesity is a global health concern that leads to metabolic alterations in the offspring, making them vulnerable to metabolic disorders in adulthood. Early identification of such neonates would provide opportunities to positively alter modifiable risk factors for non-communicable diseases (NCDs) to prevent their occurrence later in life. Objectives This study aimed to assess and contrast insulin resistance (IR) levels in neonates born to mothers with obesity and those born to healthy, non-obese mothers. Methods This case-control study was conducted after approval from the institutional ethics committee. A total of 98 healthy, non-obese pregnant females were included in Group 1, and 68 obese pregnant females were included in Group 2. The participants were followed up until delivery and cord blood samples were collected after delivery. Neonatal glucose and insulin concentrations were estimated, and indices of IR such as homeostatic model assessment for insulin resistance (HOMA-IR), quantitative insulin-sensitivity check index (QUICKI), and glucose-to-insulin ratio were calculated. Neonatal IR indices and anthropometric measurements were compared between the groups using the Z test and correlated with the maternal pre-pregnancy body mass index (BMI) using Pearson's correlation. Additionally, Pearson's correlations were examined between neonatal IR indices and anthropometric measurements. Statistical significance was set at p <0.05. Results Neonates in Group 2 exhibited significantly higher anthropometric parameters and IR indices than those in Group 1. A statistically significant positive correlation was identified between maternal pre-pregnancy BMI, neonatal anthropometric parameters, and IR. Furthermore, a statistically significant positive correlation was observed between neonatal IR and the anthropometric parameters. Conclusion Neonates born to obese mothers exhibited higher anthropometric parameters and insulin resistance than those born to non-obese, healthy mothers. Assessment of IR at birth can help identify neonates who are at higher risk of developing NCD in later life. Timely promotion of a healthy lifestyle can reduce the occurrence of NCDs in later life.
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Patients with ankylosing spondylitis (AS) have a significantly higher risk of cardiovascular morbidities. The participation of the autonomic nervous system (ANS) in AS is still unknown and inconclusive. Heart rate variability (HRV) is defined as the variability of the time interval between two consecutive heartbeats. This meta-analysis aims to detect the association of HRV and its various parameters with AS patients by comparing them to healthy controls. Research literature was searched in PubMed, Embase, and Cochrane Library databases from inception to April 2022. The Review Manager 5 (RevMan) Version 5.4 software was used to analyze the data. In addition, the protocol of systematic review is registered in the PROSPERO database with ID CRD42022336484. This study includes a total of nine case-control studies with a total of 923 patients; 409 with AS and 514 healthy controls. The root mean square of successive differences between normal heartbeats (RMSSD) [standardized mean difference (SMD); -0.47, 95% CI: -0.69 to -0.25, p < 0.0001], proportion of NN50 (pNN50) (SMD; -0.89, 95% CI: -1.74 to -0.04, p = 0.04) and HRV (SMD; -1.11, 95% CI: -1.53 to 0.69, P < 0.00001) were significantly low in AS cases compared to healthy controls. The HRV value was also significantly low in patients with high Bath ankylosing spondylitis disease activity (BASDAI) index (SMD: -1.45, 95% CI: -2.45 to -0.36, p < 0.009). HRV (parasympathetic activity) was significantly lowered in AS patients compared to healthy controls.
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Transcription factors play key roles in development and disease by controlling gene expression. Forkhead box A1 (FOXA1), is a pioneer transcription factor essential for mouse development and functions as an oncogene in prostate and breast cancer. In colorectal cancer (CRC), FOXA1 is significantly downregulated and high FOXA1 expression is associated with better prognosis, suggesting potential tumor suppressive functions. We therefore investigated the regulation of FOXA1 expression in CRC, focusing on well-differentiated CRC cells, where FOXA1 is robustly expressed. Genome-wide RNA stability assays identified FOXA1 as an unstable mRNA in CRC cells. We validated FOXA1 mRNA instability in multiple CRC cell lines and in patient-derived CRC organoids, and found that the FOXA1 3'UTR confers instability to the FOXA1 transcript. RNA pulldowns and mass spectrometry identified Staufen1 (STAU1) as a potential regulator of FOXA1 mRNA. Indeed, STAU1 knockdown resulted in increased FOXA1 mRNA and protein expression due to increased FOXA1 mRNA stability. Consistent with these data, RNA-seq following STAU1 knockdown in CRC cells revealed that FOXA1 targets were upregulated upon STAU1 knockdown. Collectively, this study uncovers a molecular mechanism by which FOXA1 is regulated in CRC cells and provides insights into our understanding of the complex mechanisms of gene regulation in cancer.
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Neoplasias Colorretais , Transcriptoma , Masculino , Humanos , Animais , Camundongos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Transcrição/metabolismo , Regulação da Expressão Gênica , Neoplasias Colorretais/metabolismo , Fator 3-alfa Nuclear de Hepatócito/genética , Fator 3-alfa Nuclear de Hepatócito/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Proteínas do Citoesqueleto/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismoRESUMO
The immune system usually provides a defense against invading pathogenic microorganisms and any other particulate contaminants. Nonetheless, it has been recently reported that nanomaterials can evade the immune system and modulate immunological responses due to their unique physicochemical characteristics. Consequently, nanomaterial-based activation of immune components, i.e., neutrophils, macrophages, and other effector cells, may induce inflammation and alter the immune response. Here, it is essential to distinguish the acute and chronic modulations triggered by nanomaterials to determine the possible risks to human health. Nanomaterials size, shape, composition, surface charge, and deformability are factors controlling their uptake by immune cells and the resulting immune responses. The exterior corona of molecules adsorbed over nanomaterials surfaces also influences their immunological effects. Here, we review current nanoengineering trends for targeted immunomodulation with an emphasis on the design, safety, and potential toxicity of nanomaterials. First, we describe the characteristics of engineered nanomaterials that trigger immune responses. Then, the biocompatibility and immunotoxicity of nanoengineered particles are debated, because these factors influence applications. Finally, future nanomaterial developments in terms of surface modifications, synergistic approaches, and biomimetics are discussed.
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Nanoestruturas , Humanos , Nanoestruturas/toxicidade , Nanoestruturas/química , Macrófagos , Inflamação , Imunidade , ImunomodulaçãoRESUMO
Despite advances in therapeutic approaches, the five-year survival rate for head and neck squamous cell carcinoma (HNSCC) patients is still less than fifty percent. Research has indicated that the consumption of Allium vegetables or processed garlic containing diallyl trisulfide (DATS) can lower the risk of multiple types of cancer. Nevertheless, the effectiveness and underlying mechanisms of DATS against HNSCC have not been thoroughly explored until the current study. In this research, it was found that DATS notably curtailed the growth and viability of HNSCC cells. Additionally, DATS triggered a significant G2/M cell cycle arrest in these cells, accumulating cyclin B1, Cip1/p21, and Ser-10 phospho-histone H3-this was indicative of mitotic arrest attenuated by NAC pretreatment, suggesting the role of reactive oxygen species (ROS) induction. The production of ROS induced by DATS led to DNA damage and apoptosis, a process associated with elevated levels of cleaved caspase-3 and cleaved PARP, along with reduced XIAP. When HNSCC cells were exposed to pharmacological concentrations of DATS, it resulted in the suppression of cancer stem cell (CSC) populations, as indicated by a decrease in the CD133high/CD44high cell fraction, reduced aldehyde dehydrogenase 1 (ALDH1) activity, inhibited spheroid formation and downregulated SOX2 and Oct4 expression. Furthermore, the administration of DATS to tumor xenografts demonstrated its in vivo capacity to hinder CSCs. Further, DATS treatment inhibited the growth of UMSCC-22B head and neck cancer tumor xenograft in immunocompromised mice. Overall, DATS inhibited cell proliferation; induced cell cycle mitotic arrest and apoptosis involving DNA damage through ROS generation; reduced the CSC fraction and spheroid formation; and downregulated SOX2 and Oct4 expression. More importantly, DATS inhibited HNSCC tumor growth and CSC fraction in vivo. Thus, DATS could be a potential anticancer agent that can be used against head and neck cancer.
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Long-term spaceflights affect the structural changes in brain, alter motor or cognitive function and associated development of neuro-optic syndrome in astronauts. Studies addressing the impact of microgravity on brain cells are very limited. Herein, we employed microglial (CHME3) and glioblastoma (U87MG and A172) cells to study their molecular and functional adaptations under simulated microgravity (SMG) exposure. A reduction in cell viability and proliferation with decreased levels of PCNA were observed in these cells. SMG caused extensive DNA damage with an increase in γH2A.X (ser139) phosphorylation and differential activation/expression of DNA damage response (DDR) proteins including ATM, ATR, Chk1, Chk2 and p53 in all the three cell lines. Unlike CHME3, the ATM/Chk2-dependent DDR pathway was activated in glioblastoma cells suggesting a marked difference in the adaptation between normal and cancer cells to SMG. Five different classes of DNA repair pathways including BER, NER, MMR, NHEJ and HR were suppressed in both cell lines with the notable exception of NHEJ (Ku70/80 and DNA-PK) activation in U87MG cells. SMG induced mitochondrial apoptosis with increased expression of Bax, cleaved caspase-3 and cleaved poly-(ADP-ribose) polymerase, and reduced Bcl-2 level. SMG triggered apoptosis simultaneously via ERK1/2 and AKT activation, and inhibition of GSK3ß activity which was reversed by MEK1 and PI3K inhibitors. Taken together, our study revealed that microgravity is a strong stressor to trigger DNA damage and apoptosis through activation of ERK1/2 and AKT, and impairment of DNA repair capacity, albeit with a cell-type difference in DDR and NHEJ regulation, in microglial and glioblastoma cells.
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Glioblastoma , Ausência de Peso , Humanos , Glioblastoma/genética , Microglia , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Reparo do DNA , Dano ao DNARESUMO
Glycosylated hemoglobin (HbA1c) is considered a new standard for the detection of diabetes mellitus because it is more accurate than regular blood sugar tests and there is no need to take blood on an empty stomach or at a specific time. In this work, we have developed a novel optical fiber biosensor, referred to as the "WaveFlex biosensor," which operates on the principles of localized surface plasmon resonance (LSPR) plasmonic wave. The sensor is fabricated using an innovative S-tapered and waist-expanded technique, enabling it to effectively detect HbA1c. Compared to the HbA1c sensors currently in use, HbA1c optical fiber sensors possess the characteristics of high sensitivity, low cost, and strong anti-interference ability. The gold nanoparticles (AuNPs), cerium oxide (CeO2) nanorods (NRs), and tungsten disulfide (WS2) nanosheets (NSs) are functionalized to improve the effectiveness of the fiber sensor on the probe surface. AuNPs are utilized to generate LSPR by the excitation of evanescent waves to amplify the sensing signal. The CeO2-NRs can have a strong metal-carrier interaction with AuNPs, enhancing the cascade of CeO2-NRs and AuNPs. The WS2-NSs with layered fold structure have a large specific surface area. Therefore, the combination of CeO2-NRs and WS2-NSs is conducive to the binding of antibodies and the addition of sites. The functionalized antibodies on the fiber make the sensor probe capable of specific selection. The developed probe is applied to test the HbA1c solution over concentrations of 0-1000 µg/mL, and the sensitivity and limits of detection of 1.195×10-5 a.u./(µg/mL) and 1.66 µg/mL are obtained, respectively. The sensor probe is also evaluated using assays for reproducibility, reusability, selectivity, and pH. According to the findings, a novel method for detecting blood glucose based on a plasmonic biosensor is proposed.
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High-toxicity secondary metabolites called aflatoxin are naturally produced by the fungus Aspergillus. In a warm, humid climate, Aspergillus growth can be considerably accelerated. The most dangerous chemical among all aflatoxins is aflatoxin B1 (AFB1), which has the potential to cause cancer and several other health risks. As a result, food forensicists now urgently need a method that is more precise, quick, and practical for aflatoxin testing. The current study focuses on the development of a highly sensitive, specific, label-free, and rapid detection method for AFB1 using a novel humanoid-shaped fiber optic WaveFlex biosensor (refers to a plasmon wave-based fiber biosensor). The fiber probe has been functionalized with nanomaterials (gold nanoparticles, graphene oxide and multiwalled carbon nanotubes) and anti-AFB1 antibodies to enhance the sensitivity and specificity of the developed sensor. The findings demonstrate that the developed sensor exhibits a remarkable low detection limit of 34.5â nM and exceptional specificity towards AFB1. Furthermore, the sensor demonstrated exceptional characteristics such as high stability, selectivity, reproducibility, and reusability. These essential factors highlight the significant potential of the proposed WaveFlex biosensor for the accurate detection of AFB1 in diverse agricultural and food samples.
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OBJECTIVES: This study assessed the clinical safety and efficacy of bexagliflozin, a sodium-glucose cotransporter 2(SGLT2) inhibitor, in managing glycemia among patients with type 2 diabetes mellitus (T2DM). AREAS COVERED: We examined RCTs with T2DM comparing the clinical effectiveness and safety of 20 mg once daily oral dose of bexagliflozin with placebo for managing glycemia till 28 May 2023, published on databases like ClinicalTrials.gov, PubMed, Embase, and Cochrane Library. Furthermore, reduction of body weight, fasting plasma sugarr(FPG), systolic blood pressure (SBP) and the percentage of individuals who achieved glycated hemoglobin (HbA1c) of < 7% from baseline were also evaluated. The Review Manager 5 was utilized to investigate the retrieved data. EXPERT OPINION: We involved eight RCTs. Bexagliflozin was significantly superior in reducing HbA1c[least squares mean difference(LSMD) = -0.45,95% confidence interval (CI =-0.55 to -0.34,p < 0.00001], FPG [LSMD= -1.37, 95%CI =-1.73 to -1.00, p < 0.00001], body weight (LSMD= -1.77, 95%CI =-2.44 to-1.10, p < 0.00001), and SBP(LSMD= -4.11,95%CI = -6.18 to -2.03,p = 0.0001) in comparison to placebo. The safety outcomes of bexagliflozin were consistent with the placebo arm. This study concluded that bexagliflozin seems to be a promising oral anti-diabetic drug for enhancing glycemic management in adult patients with T2DM.
Bexagliflozin, a novel hypoglycemic agent, is an extremely effective SGLT2 inhibitor developed by TheracosBio to manage glycemia in T2DM. The United States Food and Drug Administration (USFDA) granted first approval of bexagliflozin on 20 January 2023, for usage as an adjunctive therapy agent alongside lifestyle changes and exercise in T2DM. All included RCTs have investigated the therapeutic efficacy and safety of bexagliflozin 20 mg concerning glycemic and extra-glycemic effects in T2DM. Bexagliflozin 20 mg significantly reduces HbA1c, FPG (glycemic effect), body weight, and SBP (extra-glycemic effect) compared to the placebo arm in T2DM. Safety data show that bexagliflozin was comparable to placebo arm and polyuria, urinary tract infection (UTI), nasopharyngitis or upper respiratory tract infection (URTI), hypoglycemia, nausea, and diarrhea were the most common non-serious adverse effects. Bexagliflozin 20 mg seems to be an effective SGLT2 inhibitor compared to the placebo arm to manage glycemia in patients with T2DM along with favorable extra-glycemic effects.
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Diabetes Mellitus Tipo 2 , Inibidores do Transportador 2 de Sódio-Glicose , Adulto , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Hemoglobinas Glicadas , Transportador 2 de Glucose-Sódio , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Peso Corporal , Glucose , Sódio/uso terapêuticoRESUMO
Oral cancer (OC) has become a significant barrier to health worldwide due to its high morbidity and mortality rates. OC is among the most prevalent types of cancer that affect the head and neck region, and the overall survival rate at 5 years is still around 50%. Moreover, it is a multifactorial malignancy instigated by genetic and epigenetic variabilities, and molecular heterogeneity makes it a complex malignancy. Oral potentially malignant disorders (OPMDs) are often the first warning signs of OC, although it is challenging to predict which cases will develop into malignancies. Visual oral examination and histological examination are still the standard initial steps in diagnosing oral lesions; however, these approaches have limitations that might lead to late diagnosis of OC or missed diagnosis of OPMDs in high-risk individuals. The objective of this review is to present a comprehensive overview of the currently used novel techniques viz., liquid biopsy, next-generation sequencing (NGS), microarray, nanotechnology, lab-on-a-chip (LOC) or microfluidics, and artificial intelligence (AI) for the clinical diagnostics and management of this malignancy. The potential of these novel techniques in expanding OC diagnostics and clinical management is also reviewed.
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Neoplasias Bucais , Lesões Pré-Cancerosas , Humanos , Inteligência Artificial , Detecção Precoce de Câncer , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/epidemiologia , Neoplasias Bucais/genética , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/genética , PrognósticoRESUMO
Human papilloma virus (HPV), one of the most common sexually transmitted infections, plays a pivotal role in head and neck cancer, primarily oral and oropharyngeal squamous cell carcinomas. HPV is a vaccine-preventable disease that also contributes to cervical cancer. Although HPV vaccination effectively protects the individual against all HPV-associated human carcinomas, the awareness of HPV vaccination and its acceptance is poor in developing nations like India. India has a very high burden of oral cancer, and, unfortunately, the morbidity and mortality rates are also high as the cancer is often detected at an advanced stage. In this review, we explore the prevalence of HPV-associated head and neck squamous cell carcinoma among the Indian population and the awareness of HPV vaccination among Indian youth. Since the prognosis for HPV-associated head and neck squamous cell carcinoma is good, early diagnosis of the cancer is crucial in improving the outcome of the treatment modalities. Efforts are needed to create and increase awareness of HPV vaccination. Routine screening for HPV infection in oral mucosa can prevent the silent epidemic from taking the lives of many young people.
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Neoplasias de Cabeça e Pescoço , Infecções por Papillomavirus , Feminino , Adolescente , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Papillomavirus Humano , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Prevalência , Papillomaviridae , VacinaçãoRESUMO
Oral cancer (OC) has emerged as a major medical and social issue in many industrialized nations due to the high death rate. It is becoming increasingly common in people under the age of 45, although the underlying causes and mechanisms of this increase remain unclear. Melatonin, as a pleiotropic hormone, plays a pivotal role in a wide variety of cellular and physiological functions. Mounting evidence supports melatonin's ability to modify/influence oral carcinogenesis, help in the reduction of the incidence of OC, and increase chemo- and radiosensitivity. Despite its potential anti-carcinogenic effects, the precise function of melatonin in the management of OC is not well understood. This review summarizes the current knowledge regarding melatonin function in anti-carcinogenesis mechanisms for OC. In addition, clinical assessment and the potential therapeutic utility of melatonin in OC are discussed. This review will provide a basis for researchers to create new melatonin-based personalized medicines for treating and preventing OC.