Emerging role of microRNAs as regulators of protein kinase C substrate MARCKS and MARCKSL1 in cancer.

MicroRNAs (miRNAs) have emerged as pivotal regulators of gene expression, playing essential roles in diverse cellular processes, including the development and progression of cancer. Among the numerous proteins influenced by miRNAs, the MARCKS/MARCKSL1 protein, a key regulator of cellular cytoskeletal dynamics and membrane-cytosol communication, has garnered significant attention due to its multifaceted involvement in various cancer-related processes, including cell migration, invasion, metastasis, and drug resistance. Motivated by the encouraging early clinical success of peptides targeting MARCKS in several pathological conditions, this review article delves into the intricate interplay between miRNAs and the MARCKS protein in cancer. Herein, we have highlighted the latest findings on specific miRNAs that modulate MARCKS/MARCKSL1 expression, providing a comprehensive overview of their roles in different cancer types. We have underscored the need for in-depth investigations into the therapeutic feasibility of targeting the miRNA-MARCKS axis in cancer, taking cues from the successes witnessed in related fields. Unlocking the full potential of miRNA-mediated MARCKS regulation could pave the way for innovative and effective therapeutic interventions against various cancer types.

Designing Cobalt(II) Complex for Chemoselective Synthesis of 2-Aryl-3-formyl indoles from Amino Alcohols and Alcohols†.

An air-stable, inexpensive, and isolable cobalt(II) complex (C1) of N-((1-methyl-1H-imidazol-2-yl)methyl)-2-(phenylselanyl)ethan amine (L1) was synthesized and characterized. The complex was used to catalyze a one-pot cascade reaction between 2-(2-aminophenyl)ethanols and benzyl alcohol derivatives. Interestingly, 2-aryl-3-formylindole derivatives were formed instead of N-alkylated or C-3 alkylated indoles. A broad substrate scope can be activated using this protocol with only 5.0 mol% catalyst loading to achieve up to 87% yield of 2-aryl-3-formylindole derivatives. The mechanistic studies suggested that the reaction proceeds through tandem imine formation followed by cyclization.

Late stage specific Rv0109 (PE_PGRS1) protein of Mycobacterium tuberculosis induces mitochondria mediated macrophage apoptosis.

Mitochondria are the powerhouse of the cell and a critical cell signalling hub that decides the fate of the cell. Mycobacterium tuberculosis (Mtb) being a successful pathogen targets and controls the host mitochondria for pathogenesis. Various effector proteins of Mtb are also known to target host mitochondria which include few proteins of a unique Proline-Glutamate/Proline-Proline-Glutamate (PE/PPE) family exclusively present in pathogenic mycobacteria, but many of them are still uncharacterized. The present study investigates one such late expressing Rv0109 (PE_PGRS1) protein of Mtb. In-silico analysis predicted the presence of mitochondria targeting signal sequences in Rv0109 and its role in regulation of cysteine type endopeptidase (caspase) activity during apoptosis. Recombinant Rv0109 gets localized to mitochondria of THP1 macrophages as shown by confocal microscopy. Rv0109 was observed to induce mitochondrial stress which resulted in mitochondrial membrane depolarization, upregulation of mitochondrial superoxides and release of Cytochrome-C in the cytoplasm through flow cytometry. Depleted intracellular ATP was observed in THP1 macrophages in response to Rv0109. This mitochondrial stress in response to Rv0109 was observed to culminate in increased expression of pro-apoptotic Bax and Bim factors and caspase activation leading to macrophage apoptosis. Since Rv0109 is a late stage specific protein expressed within granuloma; mitochondria mediated apoptosis induced by Rv0109 may be explored for its role in granuloma maintenance and pathogen persistence.

Titania Nanorod-Supported Mercaptoundecanoic Acid-Grafted Palladium Nanoparticles as a Highly Reusable Heterogeneous Catalyst for Substrate-Dependent Ullmann Coupling and Debromination of Aryl Bromides.

Herein, by implanting palladium nanoparticles (Pd NPs) onto titanium dioxide (TiO2) nanorods (NRs) through 11-mercaptoundecanoic acid (MUA), we devised a robust heterogeneous catalyst. The formation of Pd-MUA-TiO2 nanocomposites (NCs) was authenticated using Fourier transform infrared spectroscopy, powder X-ray diffraction, transmission electron microscopy, energy-dispersive X-ray analysis, Brunauer-Emmett-Teller analysis, atomic absorption spectroscopy, and X-ray photoelectron spectroscopy techniques. Pd NPs were synthesized directly onto TiO2 nanorods without the MUA support for comparative studies. As a means of evaluating the endurance and competency of Pd-MUA-TiO2 NCs compared to their counterpart (Pd-TiO2 NCs), both were used as the heterogeneous catalyst for Ullmann coupling of a wide variety of aryl bromides. When Pd-MUA-TiO2 NCs were used, the reaction produced high yields of homocoupled products (54-88%), whereas the yield was only 76% when Pd-TiO2 NCs were used. Moreover, Pd-MUA-TiO2 NCs impressed with their outstanding reusability property, allowing over 14 reaction cycles without losing efficiency. On the flip side, just after seven reaction cycles, the productivity of Pd-TiO2 NCs dropped around 50%. Presumably, the strong affinity of Pd for the thiol groups of MUA allowed for the substantial control of leaching out of Pd NPs during the reaction. Nonetheless, another crucial feature of the catalyst is that the di-debromination reaction took place with an excellent yield of 68-84% from di-aryl bromides with long alkyl chains instead of macrocyclic or dimerized products. It is worth mentioning that AAS data confirmed that only 0.30 mol % catalyst loading was sufficient to activate a broad substrate scope with large functional group tolerance.

ASSESSMENT OF QUALITY AND ADEQUACY OF PANRETINAL PHOTOCOAGULATION IN PROLIFERATIVE DIABETIC RETINOPATHY USING ULTRA-WIDEFIELD IMAGING.

PURPOSE: To assess the characteristics of completed panretinal photocoagulation (PRP), using ultra-widefield imaging in proliferative diabetic retinopathy. METHODS: Quantitative assessment of ultra-widefield imaging images of 133 patients with proliferative diabetic retinopathy with completed PRP was made using ImageJ software. The parameters assessed included distance of laser spots from the optic disk, foveal center, superior and inferior arcades, and extent of the maximum width of laser. Areas assessed were total area of the image, area of the inner limit within which laser spots are restricted, minimum areas of unlasered patches, total area lasered, and ideal area to be covered by PRP. RESULTS: Two hundred one images were assessed for the final analysis. The mean distance of laser spots was 4.2 ± 2.4 mm from the optic disk (nasal) and 6.6 ± 2.5 mm from the foveal center (temporal). The mean distance of laser spots from the superior arcade vessel was 3.2 ± 1.9 mm and 6.2 ± 4.4 mm from the inferior arcade. The mean area of the retina that should have been ideally lasered was found to be 900 ± 267 mm 2 , and the actual area lasered was found to be 681 ± 254.4 mm 2 . CONCLUSION: Approximately one-quarter area of the retina continues to remain ischemic because of the lack of inadequate coverage of PRP. Further longitudinal studies are recommended, using ultra-widefield imaging to objectively assess the adequacy of PRP and its role in modulating the course of progression of the retinopathy.

The Pharmacological Implications of Flavopiridol: An Updated Overview.

Flavopiridol is a flavone synthesized from the natural product rohitukine, which is derived from an Indian medicinal plant, namely Dysoxylum binectariferum Hiern. A deeper understanding of the biological mechanisms by which such molecules act may allow scientists to develop effective therapeutic strategies against a variety of life-threatening diseases, such as cancer, viruses, fungal infections, parasites, and neurodegenerative diseases. Mechanistic insight of flavopiridol reveals its potential for kinase inhibitory activity of CDKs (cyclin-dependent kinases) and other kinases, leading to the inhibition of various processes, including cell cycle progression, apoptosis, tumor proliferation, angiogenesis, tumor metastasis, and the inflammation process. The synthetic derivatives of flavopiridol have overcome a few demerits of its parent compound. Moreover, these derivatives have much improved CDK-inhibitory activity and therapeutic abilities for treating severe human diseases. It appears that flavopiridol has potential as a candidate for the formulation of an integrated strategy to combat and alleviate human diseases. This review article aims to unravel the potential therapeutic effectiveness of flavopiridol and its possible mechanism of action.

Novel Biocompatible Green Silver Nanoparticles Efficiently Eliminates Multidrug Resistant Nosocomial Pathogens and Mycobacterium Species.

Bacterial infection is a major crisis of 21st era and the emergence of multidrug resistant (MDR) pathogens cause significant health problems. We developed, green chemistry-based silver nanoparticles (G-Ag NPs) using Citrus pseudolimon fruit peel extract. G-Ag NPs has a spherical shape in the range of ~ 40 nm with a surface charge of - 31 Mv. This nano-bioagent is an eco-friendly tool to combat menace of MDR. Biochemical tests prove that G-Ag NPs are compatible with human red blood cells and peripheral blood mononuclear cells. There have been many reports on the synthesis of silver nanoparticles, but this study suggests a green technique for making non-cytotoxic, non-hemolytic organometallic silver nanoparticles with a high therapeutic index for possible use in the medical field. On the same line, G-Ag NPs are very effective against Mycobacterium sp. and MDR strains including Escherichia coli, Klebsiella species, Pseudomonas aeruginosa, and Acinetobacter baumannii isolated from patient samples. Based on it, we filed a patent to Indian Patent Office (reference no. 202111048797) which can revolutionize the prevention of biomedical device borne infections in hospital pre/post-operated cases. This work could be further explored in future by in vivo experimentation with mice model to direct its possible clinical utility. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01061-0.

Biosensors for the detection of Mycobacterium tuberculosis: a comprehensive overview.

Tuberculosis (TB) infection is one of the leading causes of death in the world. According to WHO reports 2019, the average rate of decrease in global TB incidences was only 1.6% per year from 2000 to 2018, besides that the global decline in TB deaths was just 11%. Therefore, the dire need for early detection of the pathogen for the successful diagnosis of TB seems justified. Mycobacterium tuberculosis secretory proteins have gained more attention as TB biomarkers, for the early diagnosis and treatment of TB. Here in this review, we elaborate on the recent advancements made in the field of piezoelectric, magnetic, optical, and electrochemical biosensors, in addition to listing their merits and setbacks. Additionally, this review also discusses the construction of biosensors through modern integrated technologies, such as combinations of analytical chemistry, molecular biology, and nanotechnology. Integrated technologies enhance the detection for perceiving highly selective, specific, and sensitive signals to detect M. tuberculosis. Furthermore, this review highlights the recent challenges and scope of improvement in numerous biosensors developed for rapid, specific, selective, and sensitive detection of tuberculosis to reduce the TB burden and successful treatment.

Three-Fold Intramolecular Ring Closing Alkene Metatheses of Square Planar Complexes with cis Phosphorus Donor Ligands P(X(CH2) mCH═CH2)3 (X = -, m = 5-10; X = O, m = 3-5): Syntheses, Structures, and Thermal Properties of Macrocyclic Dibridgehead Diphosphorus Complexes.

Reactions of cis-PtCl2(P((CH2) mCH═CH2)3)2 and Grubbs' first generation catalyst and then hydrogenations afford cis- PtCl2(P((CH2) n)3 P) ( cis-2; n = 2 m + 2 = 12 (b), 14 (c), 16 (d), 18 (e), 20 (f), 22 (g); 6-40%), derived from 3-fold interligand metatheses. The phosphite complexes cis-PtCl2(P(O(CH2) m*CH═CH2)3)2 are similarly converted to cis- PtCl2(P(O(CH2) n*O)3 P) ( cis-5; n* = 8 (a), 10 (b), 12 (c), 10-20%). The substitution products cis- PtPh2(P((CH2) n)3 P) ( cis-6c,d) and cis- PtI2(P(O(CH2)10O)3 P) are prepared using Ph2Zn and NaI, respectively. Crystal structures of cis-2c,d,f, cis-5a,b, and cis-6c show one methylene bridge that roughly lies in the platinum coordination plane and two that are perpendicular. The thermal behavior of the complexes is examined. When the bridges are sufficiently long, they rapidly exchange via an unusual "triple jump rope" motion over the PtX2 moieties. NMR data establish Δ H⧧, Δ S⧧, and Δ G298K⧧/Δ G393K⧧ values of 7.8 kcal/mol, -27.9 eu, and 16.1/18.8 kcal/mol for cis-2d, and a Δ G393K⧧ of ≥19.6 kcal/mol for the shorter bridged cis-2c. While cis-2c,g gradually convert to trans-2c,g at 150-185 °C in haloarenes, trans-2c,g give little reaction under analogous conditions, establishing the stability order trans > cis. Similar metathesis/hydrogenation sequences with octahedral complexes containing two cis phosphine ligands, fac-ReX(CO)3(P((CH2)6CH═CH2)3)2 (X = Cl, Br), give fac- ReX(CO)3( P(CH2)13 CH2)((CH2)14)( P(CH2)13 CH2) (19-50%), which are derived from a combination of interligand and intraligand metathesis. The relative stabilities of cis/ trans and other types of isomers are probed by combinations of molecular dynamics and DFT calculations.

Homeomorphic Isomerization as a Design Element in Container Molecules; Binding, Displacement, and Selective Transport of MCl2 Species (M = Pt, Pd, Ni).

The dibridgehead diphosphine ((CH2)14)3 P (1) can rapidly turn inside-out (homeomorphic isomerization) to give a mixture of in,in and out,out isomers. The exo directed lone pairs in the latter are able to scavenge Lewis acidic MCl2; cagelike adducts of the in,in isomer, trans- Cl2(P((CH2)14)3 P) (M = 2/Pt, 3/Pd, 4/Ni), then form. The NiCl2 unit in 4 may be replaced by PtCl2 or PdCl2, but 2 and 3 do not give similar substitutions. U-tubes are charged with CH2Cl2 solutions of 1 (lower phase), an aqueous solution of K2MCl4 (charging arm; M = Pt, Pd), and an aqueous solution of excess KCl (receiving arm). The MCl2 units are then transported to the receiving arm until equilibrium is reached (up to 22 d). When the receiving arm is charged with KCN, transport is much faster (ca. 100 h) and higher K2MX4 equilibrium ratios are obtained (≥96≤4). Analogous experiments with K2PtCl4/K2PdCl4 mixtures show PdCl2 transport to be more rapid. A similar diphosphine with longer methylene chains, P((CH2)18)3P, is equally effective. No transport occurs in the absence of 1, and other diphosphines or monophosphines assayed give only trace levels.

Vitamin D Deficiency in Patients With Chronic Tension-Type Headache: A Case-Control Study.

OBJECTIVE: To see the interrelation between chronic tension-type headache (CTTH) and serum vitamin D levels. BACKGROUND: Several studies have suggested an association between chronic pain and vitamin D deficiency. Anecdotal evidence suggests that vitamin D deficiency may be associated with tension-type headache and migraine. METHODS: This case-control study was carried out to examine the association between CTTH and serum 25-hydroxy vitamin (25(OH) D) levels. One hundred consecutive adult (>18 years) patients with CTTH and 100 matched healthy controls were enrolled. RESULTS: The serum 25(OH) D levels were significantly lower in CTTH patients than in the controls (14.7 vs 27.4 ng/mL). The prevalence of vitamin D deficiency (serum 25 (OH) D < 20 ng/mL) was greater in patients with CTTH (71% vs 25%). CTTH patients had a significantly high prevalence of musculoskeletal pain (79% vs 57%), muscle weakness (29%vs 10%), muscle tenderness score (7.5 vs 1.9), and bone tenderness score (3.0 vs 0.8) in comparison to controls. CTTH patients with vitamin D deficient group (<20 ng/mL) had a higher prevalence of musculoskeletal pain (58% vs 31%), muscle weakness (38%vs 7%), muscle and bone tenderness score, associated fatigue (44% vs 17%) and more prolonged course (15.5 months vs 11.2 months). A strong positive correlation was noted between serum vitamin D levels and total muscle tenderness score (R2 = 0. 7365) and total bone tenderness score (R2 = 0. 6293). CONCLUSION: Decreased serum 25(OHD) concentration was associated with CTTH. Intervention studies are required to find out if supplementation of vitamin D is effective in patients with CTTH.

Dynamin 2 along with microRNA-199a reciprocally regulate hypoxia-inducible factors and ovarian cancer metastasis.

Hypoxia-driven changes in the tumor microenvironment facilitate cancer metastasis. In the present study, we investigated the regulatory cross talk between endocytic pathway, hypoxia, and tumor metastasis. Dynamin 2 (DNM2), a GTPase, is a critical mediator of endocytosis. Hypoxia decreased the levels of DNM2. DNM2 promoter has multiple hypoxia-inducible factor (HIF)-binding sites and genetic deletion of them relieved hypoxia-induced transcriptional suppression. Interestingly, DNM2 reciprocally regulated HIF. Inhibition of DNM2 GTPase activity and dominant-negative mutant of DNM2 showed a functional role for DNM2 in regulating HIF. Furthermore, the opposite strand of DNM2 gene encodes miR-199a, which is similarly reduced in cancer cells under hypoxia. miR-199a targets the 3'-UTR of HIF-1α and HIF-2α. Decreased miR-199a expression in hypoxia increased HIF levels. Exogenous expression of miR-199a decreased HIF, cell migration, and metastasis of ovarian cancer cells. miR-199a-mediated changes in HIF levels affected expression of the matrix-remodeling enzyme, lysyloxidase (LOX). LOX levels negatively correlated with progression-free survival in ovarian cancer patients. These results demonstrate a regulatory relationship between DNM2, miR-199a, and HIF, with implications in cancer metastasis.

An Innovative Air-Oxygen Blender for Continuous Positive Airway Pressure Support in Resource-Poor Locations: A Feasibility Study.

Objectives: The objectives of this study are (i) to evaluate the feasibility of using an inexpensive air pump to maintain reliable oxygen concentration in a continuous positive airway pressure (CPAP) system and (ii) to evaluate whether an inexpensive air pump can maintain infant 02 sats >90%. Methods: This prospective study, which included 19 babies in pilot phase and 90 during extension phase, was conducted at a neonatal intensive care unit in a resource-poor academic medical center in India. The intervention involved introduction of an air pump in the CPAP delivery system. Outcome measures were oxygen concentration in the air-oxygen blend and oxygen saturation of the study babies. Results: Oxygen concentration at the outlets ranged between 56 and 70% and in the blend between 42 and 51%. Oxygen saturation ranged between 90 and 97%. Conclusion: A simple and inexpensive air pump can work as a safe and effective oxygen blender.

Identification of genes associated with persistence in Mycobacterium smegmatis.

The prevalence of bacterial persisters is related to their phenotypic diversity and is responsible for the relapse of chronic infections. Tolerance to antibiotic therapy is the hallmark of bacterial persistence. In this study, we have screened a transposon library of Mycobacterium smegmatis mc2155 strain using antibiotic tolerance, survival in mouse macrophages, and biofilm-forming ability of the mutants. Out of 10 thousand clones screened, we selected ten mutants defective in all the three phenotypes. Six mutants showed significantly lower persister abundance under different stress conditions. Insertions in three genes belonging to the pathways of oxidative phosphorylation msmeg_3233 (cydA), biotin metabolism msmeg_3194 (bioB), and oxidative metabolism msmeg_0719, a flavoprotein monooxygenase, significantly reduced the number of live cells, suggesting their role in pathways promoting long-term survival. Another group that displayed a moderate reduction in CFU included a glycosyltransferase, msmeg_0392, a hydrogenase subunit, msmeg_2263 (hybC), and a DNA binding protein, msmeg_2211. The study has revealed potential candidates likely to facilitate the long-term survival of M. smegmatis. The findings offer new targets to develop antibiotics against persisters. Further, investigating the corresponding genes in M. tuberculosis may provide valuable leads in improving the treatment of chronic and persistent tuberculosis infections.

Mycobacterium tuberculosis protein PPE15 (Rv1039c) possesses eukaryote-like SH3 domain that interferes with NADPH Oxidase assembly and Reactive Oxygen Species production.

Inhibition of Reactive Oxygen Species (ROS) is one of the strategies that Mycobacterium tuberculosis (Mtb) employs as its defence mechanism. In this study, the role of PPE15 (Rv1039c), a late-stage protein, has been investigated in modulating the cellular ROS. We discovered PPE15 to be a secretory protein that downregulates ROS generation in THP1 macrophages. Our in-silico analysis revealed the presence of a eukaryote-like SH3 (SH3e) domain in PPE15. The predicted SH3e-domain of PPE15 was found to interact with cytosolic components of NADPH Oxidase (NOX), p67phox and p47phox through molecular docking. In-vitro experiments using THP1 macrophages showed a diminished NADP/NADPH ratio, indicating reduced NOX activity. We also observed increased levels of p67phox and p47phox in the cytoplasmic fraction of PPE15 treated macrophages as compared to the plasma membrane fraction. To understand the role of the SH3e-domain in ROS modulation, this domain was deleted from the full-length PPE15 (PPE15-/-SH3). We observed an increase in cellular ROS and NADP/NADPH ratio in response to PPE15-/-SH3 protein. The interaction of PPE15-/-SH3 with p67phox or p47phox was also reduced in the cytoplasm, indicating migration of NOX subunits to the plasma membrane. Additionally, M. smegmatis expressing PPE15 was observed to be resistant to oxidative stress with significant intracellular survival in THP1 macrophages as compared to M. smegmatis expressing PPE15-/-SH3. These observations suggest that the SH3e-domain of PPE15 interferes with ROS generation by sequestering NOX components that inhibit NOX assembly at the cell membrane. Therefore, PPE15 acts like a molecular mimic of SH3-domain carrying eukaryotic proteins that can be employed by Mtb at late stages of infection for its survival. These findings give us new insights about the pathogen evading strategy of Mtb which may help in improving the therapeutics for TB treatment.

Thermodynamic, kinetic, and equilibrium studies of Cu(II), Cd(II), Ni(II), and Pb(II) ion biosorption onto treated Ageratum conyzoid biomass.

The issue of environmental contamination, particularly caused by the existence of heavy metal particles, is a major and widely recognized subject that receives substantial global attention. The remediation of Cu(II), Cd(II), Ni(II), and Pb(II) ionic metal particles from synthetic wastewater using chemically treated plant leaves of Ageratum conyzoides (TAC) as a biosorbent was investigated. The biosorption process was implemented utilizing a batch system, wherein several operational parameters were considered, including temperature, pH, agitation time, biosorbent dosage, and initial concentration of the metal ion. Langmuir, Freundlich, Temkin, and D-R isotherm models were used to evaluate equilibrium data. The analyzed parameter exhibits characteristics that were best fitted with the Langmuir isotherm. The observed biosorption capacities (qm) of Cu(II), Pb(II), Ni(II), and Cd(II) ions on the TAC were measured as 51.573, 30.49, 33.53, and 35.91 mg/g, respectively, at a temperature of 22 °C. The affinity sequence of these metal ions follows the order Cu(II) > Pb(II) > Ni(II) > Cd(II). The measured values for the biosorption free energy change (ΔG) of Cu(II), Pb(II), Cd(II), and Ni(II) metal ions ranged from -1.017 to -4.723, -1.368 to -3.612, -2.785 to -5.21, and -1.047 to -5.135 kJ/mol, respectively. The enthalpy (ΔH) for Cu(II), Pb(II), Cd(II), and Ni(II) were determined to be +19.33, +6.82, +14.83, and +38.07 kJ/mol, respectively. Similarly, the corresponding entropy changes (ΔS) for the same series of metal ions were recorded as +0.075, +0.064, +0.063, and +0.135 kJ/mol.K. The pseudo-second-order kinetic models yielded superior outcomes in comparison to the pseudo-first-order kinetic models. The findings of the experiment indicated that the TAC demonstrates favorable efficacy in extracting all four metal ions. Hence, the utilization of biomass derived from Ageratum conyzoides leaves has proven to be a viable and economically feasible approach for biosorption of all four metals.

Analysis of Vocal Signatures of COVID-19 in Cough Sounds: A Newer Diagnostic Approach Using Artificial Intelligence.

BACKGROUND: Artificial intelligence (AI) based models are explored increasingly in the medical field. The highly contagious pandemic of coronavirus disease 2019 (COVID-19) affected the world and availability of diagnostic tools high resolution computed tomography (HRCT) and/or real-time reverse transcriptase-polymerase chain reaction (RTPCR) was very limited, costly and time consuming. Therefore, the use of AI in COVID-19 for diagnosis using cough sounds can be efficacious and cost effective for screening in clinic or hospital and help in early diagnosis and further management of patients. OBJECTIVES: To develop an accurate and fast voice-processing AI software to determine voice-based signatures in discriminating COVID-19 and non-COVID-19 cough sounds for screening of COVID-19. METHODOLOGY: A prospective study involving 117 patients was performed based on online and/or offline voice data collection of cough sounds of COVID-19 patients in isolation ward of a tertiary care teaching hospital and non-COVID-19 participants using a smart phone. A website-based AI software was developed to identify the cough sounds as COVID-19 or non-COVID-19. The data were divided into three segments including training set, validation set and test set. A pre-processing algorithm was utilized and combined with Short Time Fourier Transform feature representation and Logistic regression model. A precise software was used to identify vocal signatures and K-fold cross validation was carried out. RESULT: A total of 117 audio recordings of cough sounds were collected through the developed website after inclusion-exclusion criteria out of which 52 have been marked belonging to COVID-19 positive, while 65 were marked as COVID-19 negative/unsure /never had COVID-19, which were assumed to be COVID-19 negative based on RT-PCR test results. The mean and standard error values for the accuracies attained at the end of each experiment in training, validation and testing set were found to be 67.34%±0.22, 58.57%±1.11 and 64.60%±1.79 respectively. The weight values were found to be positive which were contributing towards predicting the samples as COVID-19 positive with large spikes around 7.5 kHz, 7.8 kHz, 8.6 kHz and 11 kHz which can be used for classification. CONCLUSION: The proposed AI based approach can be a helpful screening tool for COVID-19 using vocal sounds of cough. It can help the health system by reducing the cost burden and improving overall diagnosis and management of the disease.

Potential use of cidofovir, brincidofovir, and tecovirimat drugs in fighting monkeypox infection: recent trends and advancements.

Recent years have witnessed the rise of more recent pandemic outbreaks including COVID-19 and monkeypox. A multinational monkeypox outbreak creates a complex situation that necessitates countermeasures to the existing quo. The first incidence of monkeypox was documented in the 1970s, and further outbreaks led to a public health emergency of international concern. Yet as of right now, neither vaccines nor medicines are certain to treat monkeypox. Even the inability of conducting human clinical trials has prevented thousands of patients from receiving effective disease management. The current state of the disease's understanding, the treatment options available, financial resources, and lastly international policies to control an epidemic state are the major obstacles to controlling epidemics. The current review focuses on the epidemiology of monkeypox, scientific ideas, and available treatments, including potential monkeypox therapeutic methods. As a result, a thorough understanding of monkeypox literature will facilitate in the development of new therapeutic medications for the prevention and treatment of monkeypox.

Temozolomide and flavonoids against glioma: from absorption and metabolism to exosomal delivery.

Patients with glioblastoma multiforme and anaplastic astrocytoma are treated with temozolomide. Although it has been demonstrated that temozolomide increases GBM patient survival, it has also been connected to negative immune-related adverse effects. Numerous research investigations have shown that flavonoids have strong antioxidant and chemo-preventive effects. Consequently, it might lessen chemotherapeutic medicines' side effects while also increasing therapeutic effectiveness. The need for creating innovative, secure, and efficient drug carriers for cancer therapy has increased over time. Recent research indicates that exosomes have enormous potential to serve as carriers and cutting-edge drug delivery systems to the target cell. In recent years, researchers have been paying considerable attention to exosomes because of their favorable biodistribution, biocompatibility, and low immunogenicity. In the present review, the mechanistic information of the anti-glioblastoma effects of temozolomide and flavonoids coupled with their exosomal delivery to the targeted cell has been discussed. In addition, we discuss the safety aspects of temozolomide and flavonoids against glioma. The in-depth information of temozolomide and flavonoids action via exosomal delivery can unravel novel strategies to target Glioma.