Naringenin mitigates aluminum toxicity-induced learning memory impairments and neurodegeneration through amelioration of oxidative stress.

Aluminum chloride (AlCl3) is a potent neurotoxic substance known to cause memory impairment and oxidative stress-dependent neurodegeneration. Naringenin (NAR) is a dietary flavonoid with potent antioxidant and anti-inflammatory properties which was implemented against AlCl3-induced neurotoxicity to ascertain its neuroprotective efficacy. Experimental neurotoxicity in mice was induced by exposure of AlCl3 (10 mg/kg, p.o.) followed by treatment with NAR (10 mg/kg, p.o.) for a total of 63 days. Assessed the morphometric, learning memory dysfunction (novel object recognition, T- and Y-maze tests), neuronal oxidative stress, and histopathological alteration in different regions of the brain, mainly cortex, hippocampus, thalamus, and cerebellum. AlCl3 significantly suppressed the spatial learning and memory power which were notably improved by administration of NAR. The levels of oxidative stress parameters nitric oxide, advanced oxidation of protein products, protein carbonylation, lipid peroxidation, superoxide dismutase, catalase, glutathione reductase, reduced glutathione, and the activity of acetylcholine esterase were altered 1.5-3 folds by AlCl3 significantly. Treatment of NAR remarkably restored the level of oxidative stress parameters and maintained the antioxidant defense system. AlCl3 suppressed the expression of neuronal proliferation marker NeuN that was restored by NAR treatment which may be a plausible mechanism. NAR showed therapeutic efficacy as a natural supplement against aluminum-intoxicated memory impairments and histopathological alteration through a mechanism involving an antioxidant defense system and neuronal proliferation.

Autonomic neuronal modulations in cardiac arrhythmias: Current concepts and emerging therapies.

The pathophysiology of atrial fibrillation and ventricular tachycardia that result in cardiac arrhythmias is related to the sustained complicated mechanisms of the autonomic nervous system. Atrial fibrillation is when the heart beats irregularly, and ventricular arrhythmias are rapid and inconsistent heart rhythms, which involves many factors including the autonomic nervous system. It's a complex topic that requires careful exploration. Cultivation of speculative knowledge on atrial fibrillation; the irregular rhythm of the heart and ventricular arrhythmias; rapid oscillating waves resulting from mistakenly inconsistent P waves, and the inclusion of an autonomic nervous system is an inconceivable approach toward clinical intricacies. Autonomic modulation, therefore, acquires new expansions and conceptions of appealing therapeutic intelligence to prevent cardiac arrhythmia. Notably, autonomic modulation uses the neural tissue's flexibility to cause remodeling and, hence, provide therapeutic effects. In addition, autonomic modulation techniques included stimulation of the vagus nerve and tragus, renal denervation, cardiac sympathetic denervation, and baroreceptor activation treatment. Strong preclinical evidence and early human studies support the annihilation of cardiac arrhythmias by sympathetic and parasympathetic systems to transmigrate the cardiac myocytes and myocardium as efficient determinants at the cellular and physiological levels. However, the goal of this study is to draw attention to these promising early pre-clinical and clinical arrhythmia treatment options that use autonomic modulation as a therapeutic modality to conquer the troublesome process of irregular heart movements. Additionally, we provide a summary of the numerous techniques for measuring autonomic tone such as heart rate oscillations and its association with cutaneous sympathetic nerve activity appear to be substitute indicators and predictors of the outcome of treatment.

Naringenin suppresses aluminum-induced experimental hepato-nephrotoxicity in mice through modulation of oxidative stress and inflammation.

Aluminum is a widely used metal substance in daily life activities that has been shown to cause severe hepato-nephrotoxicity with long-term exposure. Natural dietary flavonoids are being utilized as a newer pharmaceutical approach against various acute and chronic diseases. Naringenin (NAR) has shown efficient therapeutic properties, including effects against metal toxicities. However, the protective efficacy of NAR on aluminum chloride (AlCl3)-induced hepato-renal toxicity needs investigation as aluminum has shown serious environmental toxicity and bioaccumulation behavior. In this study, mice were treated with AlCl3 (10 mg/kg b.w./day) to assess toxicities, and a group of mice were co-treated with NAR (10 mg/kg b.w./day) to assess the protective effects of NAR against hepato-nephrotoxicity. The levels of blood serum enzymes, oxidative stress biomarkers, inflammatory cytokines, and the apoptosis marker caspase-3 were measured using histological examinations. NAR treatment in AlCl3-treated mice resulted in maintained levels of liver and kidney function enzymes and lipid profiles. NAR treatment attenuated oxidative stress by regulating the levels of nitric oxide, advance oxidation of protein products, protein carbonylation, and lipid peroxidation. NAR also replenished reduced antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and reduced the levels of glutathione and oxidized glutathione. NAR regulated the levels of pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) and elevated the levels of anti-inflammatory cytokines (IL-4, IL-10, and IFN-γ). The histological study further confirmed the protective effects of NAR against AlCl3-induced hepato-renal alterations. NAR decreased the expression of caspase-3 as a mechanism of protective effects against apoptotic damage in the liver and kidney of AlCl3-treated mice. In summary, this study demonstrated the antioxidant and anti-inflammatory properties of NAR, leading to the suppression of AlCl3-triggered hepato-renal apoptosis and histological alterations. The results suggest that aluminum toxicity needs to be monitored in daily life usage, and supplementation of the natural dietary flavonoid naringenin may help maintain liver and kidney health.

Case Report: Primary Ewing Sarcoma of the Penis.

Background: Ewing sarcoma is a malignancy that commonly affects the skeletal system and primary extraskeletal involvement is rare. Extraskeletal Ewing sarcoma (EES) arises in soft tissue anywhere in the body. These are very rarely seen aggressive tumours. There have been only 7 reported cases of EES of penis. Case Presentation: We report a 22-year-young patient who presented to our hospital with a ulcero-proliferative growth in the shaft of penis. There were no other complaints indicating any metastasis. Incisional biopsy was suggestive of invasive malignancy. He was scheduled for a partial penectomy. Final HPE and IHC were suggestive of EES. Conclusion: EES as a subtype of Ewing sarcoma is rare and it can occur in any soft tissue site. Hence, clinicians need to differentiate this entity from other soft tissue sarcomas. Early diagnosis and timely treatment of EES are pivotal for a favourable prognosis due to its aggressive nature. Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-023-01793-x.

Naringenin ameliorates aluminum toxicity-induced testicular dysfunctions in mice by suppressing oxidative stress and histopathological alterations.

Environmental aluminum intoxication has shown increasingly alarming negative consequences on reproductive health. This needs mechanistic exploration and preventive management using medicines like herbal supplementation. The ameliorative effects of naringenin (NAR) against AlCl3-induced reproductive toxicity were thus evaluated in this study by assessing testicular dysfunction in albino male mice. A group of mice was treated with AlCl3 (10 mg/kg b.w./day) and then with NAR (10 mg/kg b.w./day) for a total of sixty-two days. Results show that treatment of AlCl3 significantly reduced the body weight and testis weight of mice. AlCl3 caused oxidative damage in mice as evidenced by an increase in the concentration of nitric oxide, advanced oxidation of protein product, protein carbonylation, and lipid peroxidation. Furthermore, diminished activity of antioxidant moieties included superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, reduced glutathione, and oxidized glutathione. Several histological changes, such as spermatogenic cell degeneration, germinal epithelium detachment, and structural abnormalities in seminiferous tubules, were observed in AlCl3-treated mice. Oral administration of NAR was found to restore body weight and testes weight and ameliorated reproductive dysfunctions. NAR decreased oxidative stress, replenished the antioxidant defense system, and improved histopathological alterations in the AlCl3-treated testes. Therefore, the present study suggests that the supplementation of NAR may be a beneficial strategy to mitigate AlCl3-induced reproductive toxicity and testicular dysfunction.

Targeting prolyl-tRNA synthetase via a series of ATP-mimetics to accelerate drug discovery against toxoplasmosis.

The prolyl-tRNA synthetase (PRS) is a validated drug target for febrifugine and its synthetic analog halofuginone (HFG) against multiple apicomplexan parasites including Plasmodium falciparum and Toxoplasma gondii. Here, a novel ATP-mimetic centered on 1-(pyridin-4-yl) pyrrolidin-2-one (PPL) scaffold has been validated to bind to Toxoplasma gondii PRS and kill toxoplasma parasites. PPL series exhibited potent inhibition at the cellular (T. gondii parasites) and enzymatic (TgPRS) levels compared to the human counterparts. Cell-based chemical mutagenesis was employed to determine the mechanism of action via a forward genetic screen. Tg-resistant parasites were analyzed with wild-type strain by RNA-seq to identify mutations in the coding sequence conferring drug resistance by computational analysis of variants. DNA sequencing established two mutations, T477A and T592S, proximal to terminals of the PPL scaffold and not directly in the ATP, tRNA, or L-pro sites, as supported by the structural data from high-resolution crystal structures of drug-bound enzyme complexes. These data provide an avenue for structure-based activity enhancement of this chemical series as anti-infectives.

Capsicum annuum L. and its bioactive constituents: A critical review of a traditional culinary spice in terms of its modern pharmacological potentials with toxicological issues.

Capsicum annuum L., commonly known as chili pepper, is used as an important spice globally and as a crude drug in many traditional medicine systems. The fruits of C. annuum have been used as a tonic, antiseptic, and stimulating agent, to treat dyspepsia, appetites, and flatulence, and to improve digestion and circulation. The article aims to critically review the phytochemical and pharmacological properties of C. annuum and its major compounds. Capsaicin, dihydrocapsaicin, and some carotenoids are reported as the major active compounds with several pharmacological potentials especially as anticancer and cardioprotectant. The anticancer effect of capsaicinoids is mainly mediated through mechanisms involving the interaction of Ca2+ -dependent activation of the MAPK pathway, suppression of NOX-dependent reactive oxygen species generation, and p53-mediated activation of mitochondrial apoptosis in cancer cells. Similarly, the cardioprotective effects of capsaicinoids are mediated through their interaction with cellular transient receptor potential vanilloid 1 channel, and restoration of calcitonin gene-related peptide via Ca2+ -dependent release of neuropeptides and suppression of bradykinin. In conclusion, this comprehensive review presents detailed information about the traditional uses, phytochemistry, and pharmacology of major bioactive principles of C. annuum with special emphasis on anticancer, cardioprotective effects, and plausible toxic adversities along with food safety.

A systematic assessment of stress insomnia as the high-risk factor for cervical cancer and interplay of cervicovaginal microbiome.

Cervical cancer is a dreaded form of cancer in women, the fourth most common cancer, with around 0.3 million females suffering from this disease worldwide. Over the past several decades, global researches have focused on the mitigation of cervical lesions and cancers and have explored the impact of physiological and psychological stress and insomnia on cervical pathogenesis. Furthermore, disruption of the cervicovaginal microbiome profiles is identified as an added high-risk factor for the occurrence of cervical cancer. The physiological regulation of stress has an underlying mechanism controlled via hypothalamic pituitary adrenal (HPA) and sympatho-adrenal medullary (SAM) axes. Disruptions in these axes have been identified as the factors responsible for maintaining the homeostasis balance. Recent studies on microbiomes have offered novel ways to combat cervical cancer and cervix infection by exploring the interplay of the cervicovaginal microbiome. Moreover, the integration of various immune cells and microbiome diversity is known to act as an effective strategy to decipher the cervix biological activity. Cytokine profiling and the related immune competence, and physiological stress and insomnia impart to the regulatory networks underlying the mechanism which may be helpful in designing mitigation strategies. This review addressed the current progress in the research on cervical cancer, HPV infection, immune cell interaction, and physiological stress and insomnia with the cervicovaginal microbiome to decipher the disease occurrence and therapeutic management.

Inonotus obliquus aqueous extract prevents histopathological alterations in liver induced by environmental toxicant Microcystin.

Environmental toxicants like microcystins are known to adversely impact liver physiology and lead to the increased risk for abnormal liver function and even liver carcinoma. Chaga mushroom (Inonotus obliquus) is reported for various properties mainly antibacterial, antiallergic, anti-inflammatory, antioxidant, and anticancer properties. This study was aimed to assess the effect microcystin (MC-LR) on histopathology of liver in mice and a preventive measure by using aqueous extract of Inonotus obliquus (IOAE). Adult Balb/c mice were administered with MC-LR at 20 â€‹µg/kg body weight, per day, intraperitoneal (i.p.) for 4 weeks. IOAE was treated to one group of MC-LR mice at 200 â€‹mg/kg body weight, per oral, for 4 weeks. Histological staining for liver structural details and biochemical assays for functions were assessed. The results of the study showed that MC-LR drastically reduced the body weight of mice which were restored close to the range of control by IOAE treatment. MC-LR exposed mice showed 1.9, 1.7 and 2.2-fold increase in the levels of SGOT, SGPT and LDH which were restored by IOAE treatment as compared to control (one-fold). MC-LR exposed mice showed reduced level of GSH (19.83 â€‹± â€‹3.3 â€‹µM) which were regained by IOAE treatment (50.83 â€‹± â€‹3.0 â€‹µM). Similar observations were noted for catalase activity. Histological examinations show that MC-LR exposed degenerative changes in the liver sections which were restored by IOAE supplementation. The immunofluorescence analysis of caspase-3 counterstained with DAPI showed that MC-LR led to the increased expression of caspase-3 which were comparatively reduced by IOAE treatment. The cell viability decreased on increasing the concentration of MC-LR with 5% cell viability at concentration of 10 â€‹µg MC-LR/mL as that of control 100% Cell viability. The IC50 was calculated to be 3.6 â€‹µg/ml, indicating that MC-LR is chronic toxic to AML12 mouse hepatocytes. The molecular docking interaction of NF-κB-NIK with ergosterol peroxidase showed binding interaction between the two and showed the plausible molecular basis for the effects of IOAE in MC-LR induced liver injury. Collectively, this study revealed the deleterious effects of MC-LR on liver through generation of oxidative stress and activation of caspase-3, which were prevented by treatment with IOAE.

Double drugging of prolyl-tRNA synthetase provides a new paradigm for anti-infective drug development.

Toxoplasmosis is caused by Toxoplasma gondii and in immunocompromised patients it may lead to seizures, encephalitis or death. The conserved enzyme prolyl-tRNA synthetase (PRS) is a validated druggable target in Toxoplasma gondii but the traditional 'single target-single drug' approach has its caveats. Here, we describe two potent inhibitors namely halofuginone (HFG) and a novel ATP mimetic (L95) that bind to Toxoplasma gondii PRS simultaneously at different neighbouring sites to cover all three of the enzyme substrate subsites. HFG and L95 act as one triple-site inhibitor in tandem and form an unusual ternary complex wherein HFG occupies the 3'-end of tRNA and the L-proline (L-pro) binding sites while L95 occupies the ATP pocket. These inhibitors exhibit nanomolar IC50 and EC50 values independently, and when given together reveal an additive mode of action in parasite inhibition assays. This work validates a novel approach and lays a structural framework for further drug development based on simultaneous targeting of multiple pockets to inhibit druggable proteins.

Nailfold Videocapillaroscopy in Connective Tissue Diseases with Raynaud's Phenomenon in an Indian Population.

INTRODUCTION: Microvasculopathy is characterized by progressive structural and functional damage to the microvessels and plays a key role in the pathogenesis of various connective tissue diseases (CTD). Nailfold videocapillaroscopy is an optimal and validated method for analysis of microvascular abnormalities and is able to differentiate secondary Raynaud's phenomenon (RP) of CTD from primary RP and healthy subjects. AIM: To assess and analyze nailfold capillaroscopic findings in Indian subjects with secondary Raynaud and to compare with findings in healthy subjects. METHODS: A total of 62 study participants including cases and controls underwent nailfold videocapillaroscopy. Capillary loop length, capillary width, capillary density, presence/absence of tortuosity, giant loops, neoangiogenesis, microhemorrhages, and avascular areas were the parameters studied. RESULTS: All the quantitative and qualitative parameters studied were significantly associated with secondary RP. Mean loop length in cases of connective tissue diseases was significantly less than in the controls (225.74 µm versus 282.97 µm) (P=0.002). Capillary density was also reduced significantly in the cases as compared to the controls (4.6 versus 7.39/mm) (P<0.01), whereas it was markedly decreased in systemic sclerosis (SSc) and mixed connective tissue diseases (MCTD), and near normal in systemic lupus erythematosus (SLE). Tortuosity was the most frequent (77.4%) qualitative parameter. Scleroderma pattern was found in 62.5% of patients with SSc and in 60% with MCTD. Non-specific pattern was found in 80% of SLE cases and 50% of dermatomyositis cases. CONCLUSION: Both quantitative and qualitative capillaroscopic changes are significantly associated with secondary RP. Scleroderma pattern was predominant in SSc and MCTD, whereas non-specific pattern was predominantly found in SLE and dermatomyositis.

Andrographolide Induces Apoptosis in Gastric Cancer Cells through Reactivation of p53 and Inhibition of Mdm-2.

Andrographolide is a labdane diterpenoid isolated from Andrographis paniculata. The plant extract and andrographolide has long been used in traditional medicine practices mainly for gastrointestinal diseases and improving liver function. Andrographolide has shown various pharmacological properties including anti-inflammatory, antioxidant and anticancer activity. This study evaluated the effect of andrographolide on proliferation of human gastric carcinoma cells in relevance to p53 and Mdm-2 pathways. Andrographolide inhibited the proliferation of SGC7901 and AGS cells in a dose-dependent manner with estimated IC50 values 38 and 44 µM respectively. Effect of andrographolide on p53 activity was ascertained by using a p53 activator (RITA) which showed synergistic inhibition of cell proliferation. While andrographolide when used in combination with a p53 inhibitor (pifithrin-α) showed potent restriction over its response. Andrographolide caused decrease in mitochondrial membrane potential as an indicator of apoptotic activity. Andrographolide activated the expression of p53 protein and gene and downregulated the levels of Mdm-2 (negative regulator of p53). Andrographolide inhibited the colony formation abilities in SGC7901 in a p53-dependent manner followed by induction of mitochondrial intrinsic apoptosis through activation of caspases-9 and -3, cleavage of PARP, and inhibition of pro-apoptotic Bcl-2. Andrographolide induced p53 mediated apoptosis in gastric carcinoma cells which adds to a novel approach in anticancer therapies.

On the approximation of functions by tanh neural networks.

We derive bounds on the error, in high-order Sobolev norms, incurred in the approximation of Sobolev-regular as well as analytic functions by neural networks with the hyperbolic tangent activation function. These bounds provide explicit estimates on the approximation error with respect to the size of the neural networks. We show that tanh neural networks with only two hidden layers suffice to approximate functions at comparable or better rates than much deeper ReLU neural networks.

The phytochemical, biological, and medicinal attributes of phytoecdysteroids: An updated review.

The phytoecdysteroids (PEs) comprise a large group of biologically-active plant steroids, which have structures similar to those of insect-molting hormones. PEs are distributed in plants as secondary metabolites that offer protection against phytophagus (plant-eating) insects. When insects consume the plants containing these chemicals, they promptly molt and undergo metabolic destruction; the insects eventually die. Chemically, ecdysteroids are a group of polyhydroxylated ketosteroids that are structurally similar to androgens. The carbon skeleton of ecdysteroids is termed as cyclopentanoperhydro-phenanthrene with a ß-side chain at carbon-17. The essential characteristics of ecdysteroids are a cis-(5ß-H) junction of rings A and B, a 7-en-6-one chromophore, and a trans-(14α-OH) junction of rings C and D. Plants only synthesize PEs from mevalonic acid in the mevalonate pathway of the plant cell using acetyl-CoA as a precursor; the most common PE is 20-hydroxyecdysone. So far, over 400 PEs have been identified and reported, and a compilation of 166 PEs originating from 1998 has been previously reviewed. In the present review, we have summarized 212 new PEs reported between 1999 and 2019. We have also critically analyzed the biological, pharmacological, and medicinal properties of PEs to understand the full impact of these phytoconstituents in health and disease.

Inhibition of Plasmodium falciparum Lysyl-tRNA Synthetase via a Piperidine-Ring Scaffold Inspired Cladosporin Analogues.

Plasmodium falciparum lysyl-tRNA synthetase (PfKRS) represents a promising therapeutic anti-malarial target. Cladosporin was identified as a selective and potent PfKRS inhibitor but lacks metabolic stability. Here, we report chemical synthesis, biological evaluation and structural characterization of analogues where the tetrahydropyran (THP) frame of cladosporin is replaced with the piperidine ring bearing functional group variations. Thermal binding, enzymatic, kinetic and parasitic assays complemented with X-ray crystallography reveal compounds that are moderate in potency. Co-crystals of Cla-B and Cla-C with PfKRS reveal key atomic configurations that allow drug binding to and inhibition of the enzyme. Collectively these piperidine ring scaffold inhibitors lay a framework for further structural editing and functional modifications of the cladosporin scaffold to obtain a potent lead.

Targeting cancer cells with nanotherapeutics and nanodiagnostics: Current status and future perspectives.

Nanotechnology is reshaping health care strategies and is expected to exert a tremendous impact in the coming years offering better healthcare facilities. It has led to not only therapeutic drug delivery feasibility but also to diagnostics. Materials in the size of nano range (1-100 nm) used in the design, fabrication, regulation, and application of therapeutic drugs or devices are classified as medical nanotechnology and nanopharmacology. Delivery of more complex molecules to the specific site of action as well as gene therapy has pushed forward the nanoparticle-based drug delivery to its maximum. Areas that benefit from nano-based drug delivery systems are cancer, diabetes, infectious diseases, neurodegenerative diseases, blood disorders and orthopedic-related ailments. Moreover, development of nanotherapeutics with multi-functionalities has a considerable potential to fill the gaps that exist in the present therapeutic domain. In cancer treatment, nanomedicines have superiority over current therapeutic practices as they can effectively deliver the drug to the affected tissues, thus reducing drug toxicities. Along this line, polymeric conjugates of asparaginase and polymeric micelles of paclitaxel have recently been recommended for the treatment of various types of cancers. Nanotechnology-based therapeutics and diagnostics provide greater effectiveness with less or no toxicity concerns. Similarly, diagnostic imaging holds promising future applications with newer nano-level imaging elements. Advancements in nanotechnology have emerged to a newer direction which use nanorobotics for various applications in healthcare. Accordingly, this review comprehensively highlights the potentialities of various nanocarriers and nanomedicines for multifaceted applications in diagnostics and drug delivery, especially the potentialities of polymeric nanoparticle, nanoemulsion, solid-lipid nanoparticle, nanostructured lipid carrier, self-micellizing anticancer lipids, dendrimer, nanocapsule and nanosponge-based therapeutic approaches in the field of cancer. Furthermore, this article summarizes the most recent literature pertaining to the use of nano-technology in the field of medicine, particularly in treating cancer patients.

Global distribution of single amino acid polymorphisms in Plasmodium vivax Duffy-binding-like domain and implications for vaccine development efforts.

Plasmodium vivax (Pv) malaria continues to be geographically widespread with approximately 15 million worldwide cases annually. Along with other proteins, Duffy-binding proteins (DBPs) are used by plasmodium for RBC invasion and the parasite-encoded receptor binding regions lie in their Duffy-binding-like (DBL) domains-thus making it a prime vaccine candidate. This study explores the sequence diversity in PvDBL globally, with an emphasis on India as it remains a major contributor to the global Pv malaria burden. Based on 1358 PvDBL protein sequences available in NCBI, we identified 140 polymorphic sites within 315 residues of PvDBL. Alarmingly, country-wise mapping of SAAPs from field isolates revealed varied and distinct polymorphic profiles for different nations. We report here 31 polymorphic residue positions in the global SAAP profile, most of which map to the PvDBL subdomain 2 (α1-α6). A distinct clustering of SAAPs distal to the DARC-binding sites is indicative of immune evasive strategies by the parasite. Analyses of PvDBL-neutralizing antibody complexes revealed that between 24% and 54% of interface residues are polymorphic. This work provides a framework to recce and expand the polymorphic space coverage in PvDBLs as this has direct implications for vaccine development studies. It also emphasizes the significance of surveying global SAAP distributions before or alongside the identification of vaccine candidates.

A Perspective on Emerging Therapeutic Interventions for COVID-19.

Coronaviruses are enveloped positive-sense RNA viruses with an unusual large RNA genome and a unique replication mechanism, which are characterized by club-like spikes that protrude from their surface. An outbreak of a novel coronavirus 2019 infection has posed significant threat to the health and economies in the whole world. This article reviewed the viral replication, pathogenicity, prevention and treatment strategies. With a lack of approved treatment options for this virus, alternative approaches to control the spread of disease is in urgent need. This article also covers some management strategies which may be applied to this virus outbreak. Ongoing clinical studies related to possible treatments for COVID-19, potential vaccines, and alternative medication such as natural compounds are also discussed.

Effect of Diagnosis by Two-Dimensional Radiography Versus CBCT on Surgical Aspects of Transmigrated Impacted Mandibular Canines.

PURPOSE: The transmigration of mandibular canines is a rare clinical finding. The present study aimed to compare the effect of diagnosis by two-dimensional radiography and cone beam computed tomography on surgical aspects of transmigrated impacted mandibular canines. PATIENTS AND METHODS: A total of 20 patients (mean age 20.18 ± 3.36 years; male/female = 1.5:1), reporting to the Department of Oral and Maxillofacial Surgery with transmigrated impacted mandibular canines and planned for surgical removal, were randomly divided into two groups of ten patients each. Group A patients were diagnosed using 2D radiographs (orthopantomograms and occlusal view radiographs), and Group B patients were diagnosed using CBCT scans. The effects of the diagnosis on surgical aspects were compared in both the groups using various intraoperative and post-operative parameters. RESULTS: The operating surgeons experienced lesser operating time and more accuracy in terms of prediction of surgical approach in Group B patients than in Group A. Post-operative complications, including post-operative vitality of the adjacent tooth and lower lip paraesthesia, were seen to be more in Group A patients than in Group B. CONCLUSION: Increased precision in localization of transmigrated impacted mandibular canines was seen by using CBCT, leading to better surgical experience and lesser post-operative complications.

Goldenseal (Hydrastis canadensis L.) and its active constituents: A critical review of their efficacy and toxicological issues.

Goldenseal (Hydrastis canadensis L.) is a medicinal plant widely used in various traditional systems of medicine and as a food supplement. It has been traditionally used by Native Americans as a coloring agent and as medicinal remedy for common diseases and conditions like wounds, digestive disorders, ulcers, skin and eye ailments, and cancer. Over the years, goldenseal has become a popular food supplement in the USA and other regions. The rhizome of this plant has been used for the treatment of a variety of diseases including, gastrointestinal disorders, ulcers, muscular debility, nervous prostration, constipation, skin and eye infections, cancer, among others. Berberine is one of the most bioactive alkaloid that has been identified in different parts of goldenseal. The goldenseal extract containing berberine showed numerous therapeutic effects such as antimicrobial, anti-inflammatory, hypolipidemic, hypoglycemic, antioxidant, neuroprotective (anti-Alzheimer's disease), cardioprotective, and gastrointestinal protective. Various research finding suggest the health promoting effects of goldenseal components and their extracts. However, few studies have also suggested the possible neurotoxic, hepatotoxic and phototoxic activities of goldenseal extract and its alkaloids. Thus, large randomized, double-blind clinical studies need to be conducted on goldenseal supplements and their main alkaloids to provide more evidence on the mechanisms responsible for the pharmaceutical activity, clinical efficacy and safety of these products. Thus, it is very important to review the scientific information about goldenseal to understand about the current scenario.