Mycobacterium tuberculosis: A New Hitchhiker in the Etiopathogenesis of Periodontitis.

Periodontitis, a chronic inflammatory disease of the gums affects both the ligament and alveolar bone. Severe form of periodontal disease affects a strikingly high number of one billion adults globally. The disease permutes both the soft and hard tissues of the oral cavity leading to localized and systemic diseases. Periodontitis has a deleterious impact on systemic health causing diabetes, cardiovascular diseases, and other disease. The cause of enhanced inflammatory process is due to dysbiosis and an unregulated immune response. Innate immune response and T cells trigger uninhibited cytokine release causing an unwarranted inflammatory response. The RANK- RANKL interaction between osteoblasts, immune cells and progenitor osteoclasts results in maturation of osteoclasts which promote bone resorption. It is well established that dysbiosis of the oral cavity has been implicated in periodontitis. But emerging reports suggest that pulmonary pathogen, Mycobacterium tuberculosis (Mtb), causes extra-pulmonary diseases such as periodontitis. Many clinical case reports advocate the involvement of Mtb in periodontitis which poses a threat with the surge of tuberculosis in HIV and other immunocompromised individuals. Fostering a better understanding of the mechanism, causative agents and control on inflammatory response is imperative in prevention and treatment of periodontitis.

Current Updates on the Role of MicroRNA in the Diagnosis and Treatment of Neurodegenerative Diseases.

BACKGROUND: MicroRNAs (miRNA) are small noncoding RNAs that play a significant role in the regulation of gene expression. The literature has explored the key involvement of miRNAs in the diagnosis, prognosis, and treatment of various neurodegenerative diseases (NDD), such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). The miRNA regulates various signalling pathways; its dysregulation is involved in the pathogenesis of NDD. OBJECTIVE: The present review is focused on the involvement of miRNAs in the pathogenesis of NDD and their role in the treatment or management of NDD. The literature provides comprehensive and cutting-edge knowledge for students studying neurology, researchers, clinical psychologists, practitioners, pathologists, and drug development agencies to comprehend the role of miRNAs in the NDD's pathogenesis, regulation of various genes/signalling pathways, such as α-synuclein, P53, amyloid-ß, high mobility group protein (HMGB1), and IL-1ß, NMDA receptor signalling, cholinergic signalling, etc. Methods: The issues associated with using anti-miRNA therapy are also summarized in this review. The data for this literature were extracted and summarized using various search engines, such as Google Scholar, Pubmed, Scopus, and NCBI using different terms, such as NDD, PD, AD, HD, nanoformulations of mRNA, and role of miRNA in diagnosis and treatment. RESULTS: The miRNAs control various biological actions, such as neuronal differentiation, synaptic plasticity, cytoprotection, neuroinflammation, oxidative stress, apoptosis and chaperone-mediated autophagy, and neurite growth in the central nervous system and diagnosis. Various miRNAs are involved in the regulation of protein aggregation in PD and modulating ß-secretase activity in AD. In HD, mutation in the huntingtin (Htt) protein interferes with Ago1 and Ago2, thus affecting the miRNA biogenesis. Currently, many anti-sense technologies are in the research phase for either inhibiting or promoting the activity of miRNA. CONCLUSION: This review provides new therapeutic approaches and novel biomarkers for the diagnosis and prognosis of NDDs by using miRNA.

Novel computational and drug design strategies for inhibition of human papillomavirus-associated cervical cancer and DNA polymerase theta receptor by Apigenin derivatives.

The present study deals with the advanced in-silico analyses of several Apigenin derivatives to explore human papillomavirus-associated cervical cancer and DNA polymerase theta inhibitor properties by molecular docking, molecular dynamics, QSAR, drug-likeness, PCA, a dynamic cross-correlation matrix and quantum calculation properties. The initial literature study revealed the potent antimicrobial and anticancer properties of Apigenin, prompting the selection of its potential derivatives to investigate their abilities as inhibitors of human papillomavirus-associated cervical cancer and DNA polymerase theta. In silico molecular docking was employed to streamline the findings, revealing promising energy-binding interactions between all Apigenin derivatives and the targeted proteins. Notably, Apigenin 4'-O-Rhamnoside and Apigenin-4'-Alpha-L-Rhamnoside demonstrated higher potency against the HPV45 oncoprotein E7 (PDB ID 2EWL), while Apigenin and Apigenin 5-O-Beta-D-Glucopyranoside exhibited significant binding energy against the L1 protein in humans. Similarly, a binding affinity range of - 7.5 kcal/mol to - 8.8 kcal/mol was achieved against DNA polymerase theta, indicating the potential of Apigenin derivatives to inhibit this enzyme (PDB ID 8E23). This finding was further validated through molecular dynamic simulation for 100 ns, analyzing parameters such as RMSD, RMSF, SASA, H-bond, and RoG profiles. The results demonstrated the stability of the selected compounds during the simulation. After passing the stability testing, the compounds underwent screening for ADMET, pharmacokinetics, and drug-likeness properties, fulfilling all the necessary criteria. QSAR, PCA, dynamic cross-correlation matrix, and quantum calculations were conducted, yielding satisfactory outcomes. Since this study utilized in silico computational approaches and obtained outstanding results, further validation is crucial. Therefore, additional wet-lab experiments should be conducted under in vivo and in vitro conditions to confirm the findings.

Anti-inflammatory activities of flavonoid derivates.

Background and purpose: Flavonoids are a group of phytochemicals found abundantly in various plants. Scientific evidence has revealed that flavonoids display potential biological activities, including their ability to alleviate inflammation. This activity is closely related to their action in blocking the inflammatory cascade and inhibiting the production of pro-inflammatory factors. However, as flavonoids typically have poor bioavailability and pharmacokinetic profile, it is quite challenging to establish these compounds as a drug. Nevertheless, progressive advancements in drug delivery systems, particularly in nanotechnology, have shown promising approaches to overcome such challenges. Review approach: This narrative review provides an overview of scientific knowledge about the mechanism of action of flavonoids in the mitigation of inflammatory reaction prior to delivering a comprehensive discussion about the opportunity of the nanotechnology-based delivery system in the preparation of the flavonoid-based drug. Key results: Various studies conducted in silico, in vitro, in vivo, and clinical trials have deciphered that the anti-inflammatory activities of flavonoids are closely linked to their ability to modulate various biochemical mediators, enzymes, and signalling pathways involved in the inflammatory processes. This compound could be encapsulated in nanotechnology platforms to increase the solubility, bioavailability, and pharmacological activity of flavonoids as well as reduce the toxic effects of these compounds. Conclusion: In Summary, we conclude that flavonoids and their derivates have given promising results in their development as new anti-inflammatory drug candidates, especially if they formulate in nanoparticles.

Omental torsion: diagnostic challenge in patients with sclerosing cholangitis and inflammatory bowel disease - case report.

Introduction and importance: The omentum appears as an apron-like extension of the peritoneum. Case presentation: A 30-year-old male patient, presented to the emergency department with the chief complaints of acute nonradiating pain localized in the right-side abdomen for the past 3 days. The patient had a past medical history of sclerosing cholangitis (SC) with inflammatory bowel disease (IBD). The patient reported the pain as persistent, pressure-like, and moderate. The patient also had a low-grade fever and nausea at the time of admission. On examination, the vital signs were found as normal. The patient reported that the abdominal pain gets exacerbated after the meals, and increase in physical activity and movement. Due to the patient's complaints and history of SC and IBD, these were considered as the possible diagnosis. After the diagnostic procedures, the patient was finally diagnosed with OT. Clinical discussion: This report presents a case of a patient suffering from omental torsion having history of SC and IBD. During the laparoscopic procedure, the diagnosis of omental torsion was confirmed. To our knowledge, no case report of omental torsion with IBD and SC is published in the literature. Conclusion: This seems to be a major diagnostic challenge as patients with IBD almost resembles the same clinical signs and symptoms as in the omental torsion. The possibility of misdiagnosis and delayed diagnosis could result in the unfavorable outcome. Therefore, the healthcare fraternities are advised to include the rare diseases such as OT as the differential diagnosis.

Therapeutic Potential and Molecular Mechanisms of the Multitargeted Flavonoid Fisetin.

Flavonoids effectively treat cancer, inflammatory disorders (cardiovascular and nervous systems), and oxidative stress. Fisetin, derived from fruits and vegetables, suppresses cancer growth by altering cell cycle parameters that lead to cell death and angiogenesis without affecting healthy cells. Clinical trials are needed in humans to prove the effectiveness of this treatment for a wide range of cancers. According to the results of this study, fisetin can be used to prevent and treat a variety of cancers. Despite early detection and treatment advances, cancer is the leading cause of death worldwide. We must take proactive steps to reduce the risk of cancer. The natural flavonoid fisetin has pharmacological properties that suppress cancer growth. This review focuses on the potential drug use of fisetin, which has been extensively explored for its cancer-fighting ability and other pharmacological activities such as diabetes, COVID-19, obesity, allergy, neurological, and bone disorders. Researchers have focused on the molecular function of fisetin. In this review, we have highlighted the biological activities against chronic disorders, including cancer, metabolic illnesses, and degenerative illnesses, of the dietary components of fisetin.

Drug target of natural products and COVID-19: how far has science progressed?

The new coronavirus [severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] that caused a viral disease with a high risk of mortality (coronavirus disease 2019) was found toward the end of 2019. This was a significant acute respiratory syndrome. In a brief period, this virus spread throughout the entire planet, causing tremendous loss of life and economic damage. The process of developing new treatments takes time, and there are presently no recognized specific treatments to treat this infection. The most promising participants, who subsequently developed into prospective leads, were dropped from the clinical research in their latter phases. Medication that has previously acquired permission may only be repurposed for use for various medical reasons following a thorough investigation for safety and effectiveness. Because there are now no effective treatments available, natural products are being used haphazardly as antiviral medications and immunity boosters. The fundamental statement that most natural compounds have powerful antiviral action does not apply to SARS-CoV-2. Middle East respiratory syndrome coronavirus and severe acute respiratory syndrome coronavirus infections are inhibited by natural treatments. According to an in silico study, the virus' nonstructural proteins, including PLpro, Mpro, and RdRp, as well as structural proteins like the spike (S) protein, have been shown to have a strong affinity for several natural products and to be inhibited by them. The virus also suggests that it is a valid candidate for therapeutic research since it utilizes the intracellular angiotensin-converting enzyme 2 receptor of the host cell. In this study, interesting targets for SARS-CoV-2 medication development are explored, as well as the antiviral properties of some well-known natural compounds.

Linezolid-induced black hairy tongue in a patient treated for idiopathic granulomatous mastitis: a case report.

Linezolid-induced black hairy tongue (BHT) is a highly scarce adverse event of linezolid therapy. To date, there are very few reported cases in contemporary literature. The onset and mechanism of BHT are also not well understood. Case report: In this article, the authors report a case of BHT in a 28-year-old female following 5 days of therapy with linezolid. The patient recovered well within few days of discontinuation of the drug and maintaining oral hygeine. Patient reassurance and counselling was integral to the management. Discussion and conclusion: This case report and review depict a rare adverse effect of linezolid and discuss its clinical implications aiding healthcare professionals in an early diagnosis and cromulent management strategy. The authors also present a compilation of previously reported literature on linezolid-induced BHT to support the discussion.

Omicron (B.1.1.529) variant and its subvariants and lineages may lead to another COVID-19 wave in the world? -An overview of current evidence and counteracting strategies.

The highly contagious Omicron variant of SARS-CoV-2 is a recent cause of concern during the COVID-19 pandemic. The World Health Organization (WHO) has classified SARS-CoV-2 variants into variants of concern (VOCs), variants of interest (VOIs), and variants under monitoring (VUMs). VOCs were categorized as Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2). Omicron (B.1.1.529) was a further modified strain that has a short incubation period; it was called VOC by the WHO, and it became fifth on the list of variants. Omicron has spread faster than any other variant since its emergence in late 2021. Omicron is currently the only circulating VOC. The various subvariants of Omicron are BA.1 (B.1.1.529.1), BA.2 (B.1.1.529.2), BA.3 (B.1.1.529.3), BA.4, BA.5, and descendent lineages. More recently, identified Omicron subvariants and sublineages BQ.1, BQ.1.1, BA.4.6, BF.7, BA.2.75.2, XBB.1, and BF.7 have also attracted global attention. The BA.5 strain of Omicron is the most contagious and dominant subvariant globally. Recent spikes in cases in China are due to the BF.7 subvariant. With the large increase in the number of cases, there has been an increase in hospitalisations in countries worldwide. In many countries, the lifting of infection prevention protocols, such as the use of masks and physical distancing, contributes to the spread of the virus. This article highlights the potential impacts of SARS-CoV-2 variants and subvariants, which have made the pandemic far from over. Effective vaccination remains the safest option to kerb transmission of these variants. Therefore, people must be vaccinated, wear masks, perform regular hand hygiene, and observe social distancing. Additionally, genome sequencing of positive samples can help detect various virus variants; thus, mapping cases in a particular area can be performed.

Monkeypox outbreak 2022: What we know so far and its potential drug targets and management strategies.

Monkeypox is a rare zoonotic disease caused by infection with the monkeypox virus. The disease can result in flu-like symptoms, fever, and a persistent rash. The disease is currently spreading throughout the world and prevention and treatment efforts are being intensified. Although there is no treatment that has been specifically approved for monkeypox virus infection, infected patients may benefit from using certain antiviral medications that are typically prescribed for the treatment of smallpox. The drugs are tecovirimat, brincidofovir, and cidofovir, all of which are currently in short supply due to the spread of the monkeypox virus. Resistance is also a concern, as widespread replication of the monkeypox virus can lead to mutations that produce monkeypox viruses that are resistant to the currently available treatments. This article discusses monkeypox disease, potential drug targets, and management strategies to overcome monkeypox disease. With the discovery of new drugs, it is hoped that the problem of insufficient drugs will be resolved, and it is not anticipated that drug resistance will become a major issue in the near future.

Promising Marine Natural Products for Tackling Viral Outbreaks: A Focus on Possible Targets and Structure-activity Relationship.

Recently, people worldwide have experienced several outbreaks caused by viruses that have attracted much interest globally, such as HIV, Zika, Ebola, and the one being faced, SARSCoV- 2 viruses. Unfortunately, the availability of drugs giving satisfying outcomes in curing those diseases is limited. Therefore, it is necessary to dig deeper to provide compounds that can tackle the causative viruses. Meanwhile, the efforts to explore marine natural products have been gaining great interest as the products have consistently shown several promising biological activities, including antiviral activity. This review summarizes some products extracted from marine organisms, such as seaweeds, seagrasses, sponges, and marine bacteria, reported in recent years to have potential antiviral activities tested through several methods. The mechanisms by which those compounds exert their antiviral effects are also described here, with several main mechanisms closely associated with the ability of the products to block the entry of the viruses into the host cells, inhibiting replication or transcription of the viral genetic material, and disturbing the assembly of viral components. In addition, the structure-activity relationship of the compounds is also highlighted by focusing on six groups of marine compounds, namely sulfated polysaccharides, phlorotannins, terpenoids, lectins, alkaloids, and flavonoids. In conclusion, due to their uniqueness compared to substances extracted from terrestrial sources, marine organisms provide abundant products having promising activities as antiviral agents that can be explored to tackle virus-caused outbreaks.

Anxiolytic, antidepressant and antioxidant activity of the methanol extract of Canarium resiniferum leaves.

Background and aim: This study evaluated the anxiolytic, antidepressant, and antioxidant activity of the methanol extract of Canarium resiniferum (MECR) leaves, and determined the total phenolic and flavonoid contents in this extract. Experimental procedure: The anxiolytic effect of MECR (100, 200, 400 mg/kg, p. o.) was tested in mice using the elevated plus-maze (EPM) test, the hole-board test (HBT), and the light-dark box (LDB) test. Its antidepressant effect was evaluated in the tail suspension (TST) and the forced swim (FST) tests. The total phenolic (TPC) and flavonoid (TFC) content was measured using standard colorimetric assays. Antioxidant activity was determined using the DPPH radical scavenging and ferric reducing antioxidant power (FRAP) assays. Results and conclusion: MECR, at all doses, showed dose-dependent anxiolytic activity. At 400 mg/kg, it significantly increased the time spent and number of entries in the open arms (EPM test), the number of head-dips (HBT), and the time spent into the light compartment (LDB) test compared to the control. In the TST and FST, MECR dose-dependently reduced the duration of immobility compared to untreated animals. This was significant for all doses except for 100 mg/kg in the FST model. MECR showed high TPC and TFC (90.94 ± 0.75 mg GAE/g and 51.54 ± 0.78 mg QE/g of dried extract, respectively) and displayed potent activity in the DPPH radical scavenging (IC50 = 177.82 µg/mL) and FRAP assays. These findings indicate that C. resiniferum has the potential to alleviate anxiety and depression disorders, which merits further exploration.

Effect of Lippia alba (Mill.) N.E. Brown Essential Oil on the Human Umbilical Artery.

Lippia alba is popularly known as lemon balm, with its essential oil (EO) cited for displaying antimicrobial, sedative, and vasorelaxant effects. Yet, its action on isolated human vessels has not been described in the literature. Thus, we evaluated the vasorelaxant effect of essential oil of L. alba (EOLa) on human umbilical arteries (HUA) isolated in organ baths. HUA rings were isolated, subjected to contractions induced by potassium chloride (KCl), serotonin (5-HT), or histamine (HIST) to record the isometric tension, and then treated with EOLa (30-1000 µg/mL). The EOLa showed a more prominent inhibitory effect on the pharmacomechanical coupling contraction via HIST with an EC50 value of 277.1 ± 8.5 µg/mL and maximum relaxant effect at 600 µg/mL. The addition of tetraethylammonium (TEA) or 4-aminopyridine (4-AP) in HUA preparations did not inhibit EOLa total relaxant effect at 1000 µg/mL. In the presence of gliblenclamide (GLI), the oil relaxed the HUA rings by 90.8% at maximum concentration. The EOLa was also investigated for its effects on voltage-operated calcium channels (VOCCs), where the HUA preincubation with this oil at 1000 µg/mL inhibited BaCl2 (0.1-30 mM)-induced contractions. This study demonstrates for the first time that EOla has a vasorelaxant effect on HUA and its particular blockade of VOCCs.

Monkeypox: A Comprehensive Review.

The 2022 multi-country monkeypox outbreak in humans has brought new public health adversity on top of the ongoing coronavirus disease 2019 (COVID-19) pandemic. The disease has spread to 104 countries throughout six continents of the world, with the highest burden in North America and Europe. The etiologic agent, monkeypox virus (MPXV), has been known since 1959 after isolation from infected monkeys, and virulence among humans has been reported since the 1970s, mainly in endemic countries in West and Central Africa. However, the disease has re-emerged in 2022 at an unprecedented pace, with particular concern on its human-to-human transmissibility and community spread in non-endemic regions. As a mitigation effort, healthcare workers, public health policymakers, and the general public worldwide need to be well-informed on this relatively neglected viral disease. Here, we provide a comprehensive and up-to-date overview of monkeypox, including the following aspects: epidemiology, etiology, pathogenesis, clinical features, diagnosis, and management. In addition, the current review discusses the preventive and control measures, the latest vaccine developments, and the future research areas in this re-emerging viral disease that was declared as a public health emergency of international concern.

Development of Microneedle Patch Loaded with Bacopa monnieri Solid Lipid Nanoparticles for the Effective Management of Parkinson's Disease.

The demand for drug delivery systems (DDS) to treat Parkinson's disease (PD) is still high, and microneedle (MN) assisted transdermal DDS offers enormous potential. Herbal products for PD have been shown to have antioxidant effects in reducing dopaminergic neurons from degeneration. Here, we attempted to incorporate solid lipid nanoparticles (SLNs) of Bacopa monnieri into dissolvable microneedle arrays and evaluate its neuroprotective activity. The bloodless and painless microneedle arrays through the transdermal route deliver the drug across the blood-brain barrier at the desired concentration. The quality by design (QbD) approach was employed for optimizing the SLNs formulations. The mechanical strength, in vitro release studies, ex-vivo permeation investigation, skin irritation test, histopathological studies, biochemical studies, and behavioural tests SLNs loaded microneedle arrays were performed. The microneedle patches obtained were shown to be mechanically robust and were also found to be nonirritant with a decreased degree of bradykinesia, high motor coordination, and balance ability. Compared to systemic delivery systems, such an MN method can achieve a considerably lower effective dose and allow long-term home-based treatment.

Design of Multi-Epitope Vaccine for Staphylococcus saprophyticus: Pan-Genome and Reverse Vaccinology Approach.

Staphylococcus saprophyticus is a Gram-positive coccus responsible for the occurrence of cystitis in sexually active, young females. While effective antibiotics against this organism exist, resistant strains are on the rise. Therefore, prevention via vaccines appears to be a viable solution to address this problem. In comparison to traditional techniques of vaccine design, computationally aided vaccine development demonstrates marked specificity, efficiency, stability, and safety. In the present study, a novel, multi-epitope vaccine construct was developed against S. saprophyticus by targeting fully sequenced proteomes of its five different strains, which were examined using a pangenome and subtractive proteomic strategy to characterize prospective vaccination targets. The three immunogenic vaccine targets which were utilized to map the probable immune epitopes were verified by annotating the entire proteome. The predicted epitopes were further screened on the basis of antigenicity, allergenicity, water solubility, toxicity, virulence, and binding affinity towards the DRB*0101 allele, resulting in 11 potential epitopes, i.e., DLKKQKEKL, NKDLKKQKE, QDKLKDKSD, NVMDNKDLE, TSGTPDSQA, NANSDGSSS, GSDSSSSNN, DSSSSNNDS, DSSSSDRNN, SSSDRNNGD, and SSDDKSKDS. All these epitopes have the efficacy to cover 99.74% of populations globally. Finally, shortlisted epitopes were joined together with linkers and three different adjuvants to find the most stable and immunogenic vaccine construct. The top-ranked vaccine construct was further scrutinized on the basis of its physicochemical characterization and immunological profile. The non-allergenic and antigenic features of modeled vaccine constructs were initially validated and then subjected to docking with immune receptor major histocompatibility complex I and II (MHC-I and II), resulting in strong contact. In silico cloning validations yielded a codon adaptation index (CAI) value of 1 and an ideal percentage of GC contents (46.717%), indicating a putative expression of the vaccine in E. coli. Furthermore, immune simulation demonstrated that, after injecting the proposed MEVC, powerful antibodies were produced, resulting in the sharpest peaks of IgM + IgG formation (>11,500) within 5 to 15 days. Experimental testing against S. saprophyticus can evaluate the safety and efficacy of these prophylactic vaccination designs.

Exploring the journey of emodin as a potential neuroprotective agent: Novel therapeutic insights with molecular mechanism of action.

Emodin is an anthraquinone derivative found in the roots and bark of a variety of plants, molds, and lichens. Emodin has been used as a traditional medication for more than 2000 years and is still common in numerous herbal drugs. Emodin is plentiful in the three plant families, including Polygonaceae (Rheum, Rumex, and Polygonum spp.), Fabaceae (Cassia spp.), and Rhamnaceae (Rhamnus, Frangula, and Ventilago spp.). Emerging experimental evidences indicate that emodin confers a wide range of pharmacological activities; special focus was implemented toward neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, cerebral ischemia, anxiety and depression, schizophrenia, chronic hyperglycemic peripheral neuropathy, etc. Numerous preclinical evidences were established in support of the neuroprotection of emodin. However, this review highlighted the role of emodin as a potent neurotherapeutic agent; therefore, its evidence-based functionality on neurological disorders (NDs).