Evaluation of Dermal Wound Healing Potential: Phytochemical Characterization, Anti-inflammatory, Antioxidant, and Antimicrobial Activities of Euphorbia guyoniana Boiss. & Reut. Latex.

This study investigates the wound-healing potential of Euphorbia guyoniana latex (EGL) in male Wistar rats, along with its biochemical composition and biological activities. Phytochemical analysis identified moderate levels of phenolics, flavonoids, and tannins, with HPLC revealing five phenolic compounds. EGL demonstrated strong antioxidant activity in DPPH assays, surpassing ascorbic acid in protecting red blood cells. Its performance in the ß-carotene-linoleic acid assay was robust, though its FRAP assay results were weaker. EGL also exhibited significant anti-inflammatory activity, comparable to Acetylsalicylic acid, and showed antibacterial effects against Listeria innocua. In Vivo, EGL-infused ointments accelerated wound healing, reducing epithelialization periods to 12-16 days, with a higher wound contraction rate compared to controls. The study concludes that EGL, rich in bioactive compounds, holds potential as a promising natural agent for wound healing, owing to its potent antioxidant, anti-inflammatory, and antibacterial properties.

Thiazine-derived compounds in inhibiting efflux pump in Staphylococcus aureus K2068, mepA gene expression, and membrane permeability alteration.

Staphylococcus aureus is a bacterium responsible for resistance to multiple drugs and the efflux system is widely studied among the resistance mechanisms developed by this species. The present study evaluates the inhibition of the MepA efflux pump by thiadiazine-derived compounds. For this purpose, thiadiazine-derived compounds (IJ-14 to IJ-20) were tested against S. aureus K2068 strains. Microdilution tests were initially conducted to assess the Minimum Inhibitory Concentration (MIC) of the compounds and their efflux pump inhibition activity. In addition, fluorimetry tests were performed using BrEt emission and tests were conducted to inhibit the expression of the mepA gene. This involved comparing the bacterial gene expression with the antibiotic alone to the gene expression after combining compounds (IJ-17 and IJ-20) with the antibiotic. Furthermore, membrane permeability assessment tests and in silico molecular docking tests were performed. It was observed that the IJ17 and IJ20 compounds exhibited direct activity against the tested strain. The IJ17 compound produced significant results in the gene inhibition tests, which was also evidenced through the membrane permeability alteration test. These findings suggest that thiadiazine-derived compounds have promising effects against one of the main resistance mechanisms, with the IJ17 compound presenting observable mechanisms of action.

Efficient Synthesis of Mannopyranoside-based Fatty Acyl Esters: Effects of Acyl Groups on Antimicrobial Potential.

BACKGROUND: The approval of Sucrose Fatty Acid Esters (SFAEs) as food additives/ preservatives with antimicrobial potential has triggered enormous interest in discovering new biological applications. Accordingly, many researchers reported that SFAEs consist of various sugar moieties, and hydrophobic side chains are highly active against certain fungal species. OBJECTIVE: This study aimed to conduct aregioselective synthesis of SAFE and check the effect of chain length and site of acylation (i.e., C-6 vs. C-2, C-3, C-4, and long-chain vs. short-chain) on antimicrobial potency. METHODS: A direct acylation method maintaining several conditions was used for esterification. In vitro tests, molecular docking, and in silico studies were conducted using standard procedures. RESULTS: In vitro tests revealed that the fatty acid chain length in mannopyranoside esters significantly affects the antifungal activity, where C12 chains are more potent against Aspergillus species. In terms of acylation site, mannopyranoside esters with a C8 chain substituted at the C-6 position are more active in antifungal inhibition. Molecular docking also revealed that these mannopyranoside esters had comparatively better stable binding energy and hence better inhibition, with the fungal enzymes lanosterol 14-alpha-demethylase (3LD6), urate oxidase (1R51), and glucoamylase (1KUL) than the standard antifungal drug fluconazole. Additionally, the thermodynamic, orbital, drug-likeness, and safety profiles of these mannopyranoside esters were calculated and discussed, along with the Structure-Activity Relationships (SAR). CONCLUSION: This study thus highlights the importance of the acylation site and lipid-like fatty acid chain length that govern the antimicrobial activity of mannopyranoside-based SFAE.

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.

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.

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.

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.