Secondary metabolites in topical infectious diseases and nanomedicine applications.

Topical infection affects nearly one-third of the world's population; it may result from poor sanitation, hygienic conditions and crowded living and working conditions that accelerate the spread of topical infectious diseases. The problems associated with the anti-infective agents are drug resistance and long-term therapy. Secondary metabolites are obtained from plants, microorganisms and animals, but they are metabolized inside the human body. The integration of nanotechnology into secondary metabolites is gaining attention due to their interaction at the subatomic and skin-tissue levels. Hydrogel, liposomes, lipidic nanoparticles, polymeric nanoparticles and metallic nanoparticles are the most suitable carriers for secondary metabolite delivery. Therefore, the present review article extensively discusses the topical applications of nanomedicines for the effective delivery of secondary metabolites.

Emergence of Nano-Based Formulations for Effective Delivery of Flavonoids against Topical Infectious Disorders.

Flavonoids are hydroxylated phenolic substances in vegetables, fruits, flowers, seeds, wine, tea, nuts, propolis, and honey. They belong to a versatile category of natural polyphenolic compounds. Their biological function depends on various factors such as their chemical structure, degree of hydroxylation, degree of polymerization conjugation, and substitutions. Flavonoids have gained considerable attention among researchers, as they show a wide range of pharmacological activities, including coronary heart disease prevention, antioxidative, hepatoprotective, anti-inflammatory, free-radical scavenging, anticancer, and anti-atherosclerotic activities. Plants synthesize flavonoid compounds in response to pathogen attacks, and these compounds exhibit potent antimicrobial (antibacterial, antifungal, and antiviral) activity against a wide range of pathogenic microorganisms. However, certain antibacterial flavonoids have the ability to selectively target the cell wall of bacteria and inhibit virulence factors, including biofilm formation. Moreover, some flavonoids are known to reverse antibiotic resistance and enhance the efficacy of existing antibiotic drugs. However, due to their poor solubility in water, flavonoids have limited oral bioavailability. They are quickly metabolized in the gastrointestinal region, which limits their ability to prevent and treat various disorders. The integration of flavonoids into nanomedicine constitutes a viable strategy for achieving efficient cutaneous delivery owing to their favorable encapsulation capacity and diminished toxicity. The utilization of nanoparticles or nanoformulations facilitates drug delivery by targeting the drug to the specific site of action and exhibits excellent physicochemical stability.

Potential therapeutic application of biophenols - plants secondary metabolites in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease showed that persistent inflammation in the joints, induces the cartilage destruction, bone erosion, and leukocyte infiltration in the synovium. RA mostly affects the joints of hands, feet, wrists, ankles, and knees. Each year, approximately 20-40 new cases are reported per lac population and the disease affects women more than men. The etiology of RA is still unknown, but many pathways have been identified as potential targets in its pathophysiology, including the PI3K/AKT signaling pathway, NF-κB signaling, Adenosine signaling, Wnt, SYK/BTK, and mTOR signaling pathways. Biophenol, plant secondary metabolite, is considered one of the most abundantly phytoconstituents to have potential anti-inflammatory effects associated with multiple pathways. These indicate that biophenols can be used for its protective effect on the development and symptoms of RA. The current review explores and discusses the role of different biophenols in the treatment of RA disease.

Prospective Challenges for Patenting and Clinical Trials of Anticancer Compounds from Natural Products: Coherent Review.

Cancer is a leading cause of morbidity and mortality worldwide. Each year, millions of people worldwide are diagnosed with cancer, and more than half of them die. Various conventional therapies for cancer, including chemotherapy and radiotherapy, have extreme side effects. Therefore, to minimize the global burden of lethal diseases like cancer, an effective and novel drug must be discovered. Its patent should be acquired to secure the novel medicament. The pharmacological potential of different natural products has made them popular in the healthcare and pharmaceutical industries. Various anticancer compounds are obtained from natural sources such as plants, microbes, and marine and terrestrial animals, including alkaloids, terpenoids, biophenols, enzymes, glycosides, etc. The term "natural products" is defined as the product of secondary or non-essential metabolic processes produced by living organisms (such as plants, invertebrates, and microorganisms). Although more precise definitions of NPs exist, they do not always meet consensus. Others define NPs as small molecules (excluding biomolecules) that emerge from the metabolic reaction. A handful of effective compounds are used currently from natural or analog moieties, and many more are in clinical studies. There is an excellent need for patenting molecules from natural products as the hit lead molecules are derived, isolated, and synthesized from natural products. However, these naturally occurring products may not be patentable under the law because they come from nature. This review highlights why natural products and compounds are hard to patent, under what patent law criteria we can patent these natural products and compounds, patent procedural guideline sources and why researchers prefer publication rather than a patent. Here, various patent scenarios of natural products and compounds for cancer have been given.

Nanomedicine-Based Drug-Targeting in Breast Cancer: Pharmacokinetics, Clinical Progress, and Challenges.

Breast cancer (BC) is a malignant neoplasm that begins in the breast tissue. After skin cancer, BC is the second most common type of cancer in women. At the end of 2040, the number of newly diagnosed BC cases is projected to increase by over 40%, reaching approximately 3 million worldwide annually. The hormonal and chemotherapeutic approaches based on conventional formulations have inappropriate therapeutic effects and suboptimal pharmacokinetic responses with nonspecific targeting actions. To overcome such issues, the use of nanomedicines, including liposomes, nanoparticles, micelles, hybrid nanoparticles, etc., has gained wider attention in the treatment of BC. Smaller dimensional nanomedicine (especially 50-200 nm) exhibited improved in vivo effectiveness, such as better tissue penetration and more effective tumor suppression through enhanced retention and permeation, as well as active targeting of the drug. Additionally, nanotechnology, which further extended and developed theranostic nanomedicine by incorporating diagnostic and imaging agents in one platform, has been applied to BC. Furthermore, hybrid and theranostic nanomedicine has also been explored for gene delivery as anticancer therapeutics in BC. Moreover, the nanocarriers' size, shape, surface charge, chemical compositions, and surface area play an important role in the nanocarriers' stability, cellular absorption, cytotoxicity, cellular uptake, and toxicity. Additionally, nanomedicine clinical translation for managing BC remains a slow process. However, a few cases are being used clinically, and their progress with the current challenges is addressed in this Review. Therefore, this Review extensively discusses recent advancements in nanomedicine and its clinical challenges in BC.

Guava Leaf Essential Oil as a Potent Antioxidant and Anticancer Agent: Validated through Experimental and Computational Study.

Several drugs now employed in cancer therapy were discovered as a result of anticancer drug research based on natural products. Here, we reported the in vitro antioxidant and anticancer activity followed by in silico anticancer and estrogen-like activity of Psidium guajava L. essential oil against ER-α receptors which lead to potential inhibitory action against breast cancer pathways. METHODS: The bioactive compounds in guava essential oil were screened using gas chromatography-mass spectrometry (GC-MS). Similarly, the antioxidant properties of the extracted oil were evaluated using 2,2-Diphenyl-1-picrylhydrazyl scavenging assay. Furthermore, the in vitro anticancer activity of guava oil was observed through the MTT assay and an in silico molecular docking experiment was also carried out to ensure that they fit into the estrogen receptors (ERs) and possess anticancer potential. RESULTS: The GC-MS profile of the essential oil revealed the presence of 17 chemicals, with limonene (51.3%), eucalyptol (21.3%), caryophyllene oxide (6.2%), caryophyllene (5.6%), and nerolidol (4.5%) occupying more than one-third of the chromatographic spectrum zone. Guava leaves' essential oil (EO) inhibited DPPH (2,2-diphenyl-1-picrylhydrazyl) radicals and exhibited concentration dependent free radical scavenging activity, acting as a potent antioxidant with an IC50 value of 29.3 ± 0.67 µg/mL. The outcome of the MTT assay showed that the extracted guava oil had nearly the same efficacy against breast and liver cancer cells at a low concentration (1 µg/mL), giving 98.3 ± 0.3% and 98.5 ± 0.4% cell viability against HepG2 at 1 µg/mL, respectively. When the concentration of essential oil was increased, it showed a small reduction in the percentage of viable cells. While conducting an in silico study of all the screened compounds, the potential for hydroxycaryophyllene, caryophyllene, caryophyllene oxide, humulene, terpineol, and calamenene to inhibit tumor growth was bolstered due to a resemblance to 4-hydroxytamoxifen, thereby implying that these compounds may act as selective estrogen receptor modulators (SERMs). The ADME analysis of the compounds indicated above revealed that they exhibit excellent drug likeness properties and follow the Lipinski rule of five. CONCLUSIONS: Consequently, they have a substantial anticancer therapeutic potential and can be used for novel drug discovery in the effort to minimize the global burden of breast cancer.

In Vitro Antioxidant and Antimicrobial Potency of Mimosa pudica of Nepalese Terai Region: Insight into L-Mimosine as an Antibacterial Agent.

Aim: The study aimed to evaluate the in vitro antioxidant and antimicrobial potency of Mimosa pudica found wildly in the Terai region of Nepal and assess its physicochemical properties, such as total phenolic content (TPC) and total flavonoid content (TFC). Materials and Methods: The physicochemical properties of ethyl acetate extract of Mimosa pudica (EAMP), such as extractive value, total ash content, loss on drying, and phytochemical screening, were calculated using standard protocols. The TPC was determined by using the Folin-Ciocalteu method taking gallic acid as standard, and TFC was conducted by using the AlCl3 colorimetric method, using a 96-well plate reader. The in vitro antibacterial activity of different concentrations of the extract against four bacterial ATCC strains was determined by the agar well diffusion method in the Mueller Hinton agar (MHA) medium. The in silico molecular docking model was used to ascertain the antibacterial potency of L-mimosine against the selected strains of bacteria used for the in vitro study by calculating the binding affinity towards the protein of bacteria. Results: The preliminary screening of the extract showed the presence of several phytochemicals. The total ash content (7.67%), loss on drying (2.30%), and extractive value (8.966%) were determined by analyzing the crude sample. The total phenolic and flavonoid contents were 418.640 ± 0.018 mg GAE/g (dried extract) and 14.126 ± 0.021 mg QE/g (dried extract), respectively. The extract showed a potent free radical scavenging activity with an IC50 value of 158.95 ± 1.12 µg/mL. The plant extract also demonstrated the antibacterial activity against both Gram-positive bacteria Staphylococcus aureus (15 mm) and Bacillus cereus (22 mm) and Gram-negative bacteria Escherichia coli (17 mm) and Klebsiella pneumoniae (16 mm) at 200 mg/mL concentration of extract. There was a noteworthy binding affinity of antibiotics with almost all selected bacterial proteins with binding energy against Escherichia coli DNA gyrase subunit B (-5.7 kcal/mol), Staphylococcus aureus DNA gyrase subunit B (-6.1 kcal/mol), Bacillus cereus metallothiol transferase (-5.2 kcal/mol), and Klebsiella pneumoniaebeta-lactamase (-6.1 kcal/mole), respectively, with the L-mimosine. Conclusion: The findings of the current study suggest that Mimosa pudica from the Terai region of Nepal is rich in phenolic and flavonoid compounds, has a significant impact on bacterial growth inhibition, and has a notable potential to scavenge free radicals (DPPH). According to the in silico analysis, L-mimosine is a potent antibacterial compound that might be utilised to discover novel antibacterial drugs to combat antibiotic resistance.

Current Research on Zinc Oxide Nanoparticles: Synthesis, Characterization, and Biomedical Applications.

Zinc oxide nanoparticles (ZnO-NPs) have piqued the curiosity of researchers all over the world due to their extensive biological activity. They are less toxic and biodegradable with the capacity to greatly boost pharmacophore bioactivity. ZnO-NPs are the most extensively used metal oxide nanoparticles in electronic and optoelectronics because of their distinctive optical and chemical properties which can be readily modified by altering the morphology and the wide bandgap. The biosynthesis of nanoparticles using extracts of therapeutic plants, fungi, bacteria, algae, etc., improves their stability and biocompatibility in many biological settings, and its biofabrication alters its physiochemical behavior, contributing to biological potency. As such, ZnO-NPs can be used as an effective nanocarrier for conventional drugs due to their cost-effectiveness and benefits of being biodegradable and biocompatible. This article covers a comprehensive review of different synthesis approaches of ZnO-NPs including physical, chemical, biochemical, and green synthesis techniques, and also emphasizes their biopotency through antibacterial, antifungal, anticancer, anti-inflammatory, antidiabetic, antioxidant, antiviral, wound healing, and cardioprotective activity. Green synthesis from plants, bacteria, and fungus is given special attention, with a particular emphasis on extraction techniques, precursors used for the synthesis and reaction conditions, characterization techniques, and surface morphology of the particles.

Knowledge, practices and compliance related to COVID-19 among Nepalese population in Province 2, Nepal.

Aim: The study aimed to access the knowledge, practice, and compliance related to COVID-19 among people residing in Province 2, Nepal. Materials and methods: A descriptive cross-sectional study was conducted from October 2020 to March 2021. A total of 457 participants of eight districts of Province 2 were enrolled after obtaining consent. Data were collected by face-to-face interviews with participants. A total of 31 validated pre-structured questionnaires were asked to participants in which 11 questions were for knowledge, 12 questions were for practices, and 8 questions were for compliance related to COVID-19. For tool validation, pre-testing was done in 10.0% of individuals of the targeted study population of Mahottari district. Results: Out of 457 participants, 353(77.2%) were male. The majority of the participants were unmarried (68.3%), had only school-level education (26.5%), Hindu by religion (89.7%), farmers (23.0%), and businessmen (23.0%). More than 75.0% of individuals had knowledge about the causative agent of COVID-19 symptoms and the purpose of isolation. About 53.8% of participants had good knowledge of social distancing, 31.1% had knowledge of masks, and 39.3% knew about sanitizer. Moreover, 94.3% of the respondents had good knowledge of hand-washing practice with soap-water and use of sanitizer, 89.1% had good knowledge of wearing masks and 82.9% followed social distancing. Compliance with standard procedures of sneezing was recorded in 43.1%, washing hands with soap water/sanitizer was 82.3%, and disposal of masks was 53.6%. A significant association was observed between gender with knowledge and compliance (p < 0.05). District-wise association with knowledge, practice and compliance was found to be significant (p < 0.05). Conclusion: The findings suggest that participants have a good level of knowledge; however, the practice and compliances are considerably low related to COVID-19.

A cross talk between the immunization and edible vaccine: Current challenges and future prospects.

INTRODUCTION: It is well known that immune system is highly specific to protect the body against various environmental pathogens. The concept of conventional vaccination has overcome the pandemic situation of several infectious diseases outbreak. AREA COVERED: The recent idea of immunization through oral route (edible vaccine) is vital alternatives over conventional vaccines. Edible vaccines are composed of antigenic protein introduced into the plant cells which induce these altered plants to produce the encoded protein. Edible vaccine has no way of forming infection and safety is assured as it only composed of antigenic protein and is devoid of pathogenic genes. Edible vaccines have significant role in stimulating mucosal immunity as they come in contact with digestive tract lining. They are safe, cost-effective, easy-to-administer and have reduced manufacturing cost hence have a dramatic impact on health care in developing countries. EXPERT OPINION: The edible vaccine might be the solution for the potential hazard associated with the parenteral vaccines. In this review we discuss the detailed study of pros, cons, mechanism of immune stimulation, various outbreaks that might be controlled by edible vaccines with the possible future research and applied application of edible vaccine.

Coupled plate-string vibrations in the presence of a finite bridge: Effect on natural frequencies and harmonicity.

Harmonicity of natural frequencies is investigated for a string vibrating against a finite bridge mounted on a flexible plate. This coupled system is akin to the vibration of strings in musical instruments like the sitar, where the top plate is approximated as a clamped circular plate. The bridge is assumed to be parabolic and rigidly attached to the plate at one point. For simplicity, the plate is replaced by linear and torsional springs with frequency dependent dynamic stiffness to account for the continuous nature of the plate. Governing equations of motions are obtained using Hamilton's principle, which are linearized about the static configuration. It is observed that the coupled natural frequencies below the first structural frequencies are inharmonic in a manner opposed to the inharmonicity due to the bending rigidity of the string. A detailed parametric study on the effect of plate thickness, position, mass, and geometry of the bridge on the natural frequencies is performed. It is found that a proper choice of these parameters can significantly increase the harmonic content in the frequencies for real strings. This study guides the proper choice of system parameters to obtain better harmonic relation between the coupled structure-string modes with real strings.

Assessment of nail unit structures by ultrasound in patients with psoriatic arthritis and their correlations with disease activity indices: a case-control study.

Ultrasound (USG) of nail was performed to assess, (1) morphological alterations of nail plates in psoriatic arthritis (PsA) patients, (2) differences of nail unit parameters [nail bed thickness (NBT), nail matrix thickness (NMT) and nail plate distance (NPD)] in PsA patients from healthy controls (3) correlation of nail unit parameters with PsA disease activity indices. Total of 895 fingernails (448 nails of 45 PsA patients and 447 of 45 controls) were evaluated by USG. Psoriasis Area and Severity Index (PASI), Disease Activity in Psoriatic Arthritis (DAPSA), and Nail Psoriasis Severity Index (NAPSI) were calculated in PsA patients. Nail unit parameters were compared between two study groups. Correlation study was done between nail unit parameters and disease activity indices. All PsA patients showed ultrasound evidence of nail plate changes (87.95% of the total fingernails and 75.34% of the clinically normal nails). Loosening of the ventral nail plate border was most common (51.79%). Mean NBT (PsA: 0.19 ± 0.035 cm, control: 0.17 ± 0.018 cm, p = 0.003) and mean NMT (PsA: 0.32 ± 0.041 cm, control: 0.28 ± 0.031 cm, p = < 0.0001) were significantly increased in the PsA patients. Moderately positive correlation was observed between NAPSI score and mean NMT (Spearman r = 0.411, 95% confidence interval: 0.125-0.634, p = 0.005). USG evidence of nail plate alterations was frequent among PsA patients, even in clinically normal nails. Increased mean nail bed and matrix thickness were noted in PsA patients. Mean NMT had a moderately positive correlation with NAPSI score.

Nanomechanical responses of human hair.

Here we report the first ever studies on nanomechanical properties e.g., nanohardness and Young׳s modulus for human hair of Indian origin. Three types of hair samples e.g., virgin hair samples (VH), bleached hair samples (BH) and Fe-tannin complex colour treated hair samples (FT) with the treatment by a proprietary hair care product are used in the present work. The proprietary hair care product involves a Fe-salt based formulation. The hair samples are characterized by optical microscopy, atomic force microscopy, field emission scanning electron microscopy, energy dispersive X-ray spectroscopy (EDAX) genesis line map, EDAX spot mapping, nanoindentation, tensile fracture, and X-ray diffraction techniques. The nanoindentation studies are conducted on the cross-sections of the VH, BH and FT hair samples. The results prove that the nanomechanical properties e.g., nanohardness and Young׳s modulus are sensitive to measurement location e.g., cortex or medulla and presence or absence of the chemical treatment. Additional results obtained from the tensile fracture experiments establish that the trends reflected from the evaluations of the nanomechanical properties are general enough to hold good. Based on these observations a schematic model is developed. The model explains the present results in a qualitative yet satisfactory manner.

Unilateral supernumerary kidney with contra lateral hydronephrosis-a rare case report.

Supernumerary kidney is the rarest of all renal anomalies; fewer than 80 cases have been reported in the literature over the years. Supernumerary kidneys are most commonly located on the left side of the abdomen. Different pathologic conditions are reported to affect supernumerary kidneys and they may be associated with malformations of the upper urinary tract and genital tract. Because of their infrequent occurrence and reporting, they frequently cause diagnostic challenges. Here we report a case in a 14-year-old male patient of unilateral supernumerary kidney on the right side of the abdomen with multiple calculi, mal-rotation and a gross hydronephrotic left kidney.