Therapeutic potential of clinically proven natural products in the management of dementia.

Dementia is a common neurodegenerative disorder connected to damage to nerve cells in the brain. Although some conventional drugs are available for dementia treatments and are still sanctified for dementia patients, their short- and long-term side effects and other limitations make treating patients more challenging. The authors aimed to explain novel options for treating dementia with natural products and unravel some clinically proven natural products. This article systematically reviewed recent studies that have investigated the role of natural products and their bioactive compounds for dementia. PubMed Central, Scopus, and Google Scholar databases of articles were collected, and abstracts were reviewed for relevance to the subject matter.In this review, we provide mechanistic insights of clinically validated natural products, including like- Yokukansan, Souvenaid, BDW, Hupergene, Bacopa monnier, Omega-3, Tramiprostate and Palmitoylethanolamide with which have therapeutic efficacy against dementia in the management of dementia. As shown by studies, certain natural ingredients could be used to treat and prevent dementia. We strongly believe that the medicinal plants and phytoconstituents alone or in combination with other compounds would be effective treatments against dementia with lesser side effects as compared to currently available treatments. Moreover, these products should be studied further in order to develop novel dementia medications.

A comprehensive review on clinically proven natural products in the management of nerve pain, with mechanistic insights.

Introduction: People are treating their neuropathic pain with several approved and licensed pharmacological drugs. But due to having existing limitations like low efficacy with some side effects, there needs to be a more effective alternative and complementary therapeutic options. Purpose: s: The study was designed to discuss the mechanistic role of several clinically proven natural products that have been shown to play a significant role against different nerve pain or neuropathic pain. Method: ology: Information for this review article was salvaged using several accessible searching databases like SciVerse Scopus ® (Elsevier Properties S. A, USA), Web of Science® (Thomson Reuters, USA), and PubMed® (U.S. National Library of Medicine, USA) considering some search items like - nerve pain, natural products in pain/nerve pain management, clinically proven natural products in pain management, pain-reducing agents and so on. Result: Our study reported the therapeutic efficacy of natural products and their possible mechanism against neuropathic pain in the human body. Natural products widely used to treat neuropathic pain include comfrey root extract ointment, lavender oil, Rose Oil, aromatic essential oil, ginger oil, vitex agnus-castus, peganum oil, and ajwain 10%. Some common pathways are involved in pain relief through sensory stimulation, enzymatic, anti-inflammatory, and pain-related receptor regulation. Conclusion: The present study suggests that the mentioned natural products can be an appropriate choice for the treatment and management of neuropathic pain.

Morphological Patterns of Balanoposthitis and their Correlation with Final Etiological Diagnosis.

Background: Balanoposthitis is a common dermatological condition across the globe, but studies describing clinico-morphologic features and their diagnostic correlates are scarce. Objective: To study various morphological patterns of balanoposthitis and their correlation with etiological diagnosis. Materials and Methods: A cross-sectional study was conducted on all patients with balanoposthitis visiting the dermatology out-patient department and sexually transmitted disease (STD) clinic over a period of 8 months. Detailed history, demographic data, and clinical features were recorded. Relevant investigations were performed. Results: A total of 129 patients of balanoposthitis were studied. Common causes were because of candida (33.3%), bacteria (17.1%), irritants (13.3%), herpes (11.4%), drugs (8.6%), and lichen sclerosus (6.7%). Common morphological patterns were erosion/confluent wet erythema with sub-preputial discharge (24.81%), fissure with superficial pustules (15.5%), fissure alone (13.18%), patchy dry erythema (11.63%), and superficial pustules (intact or exfoliated) with or without underlying erythema (10.85%). Fissure and superficial pustules were the most common presentation of candidal balanoposthitis (51.43%), erosions/confluent wet erythema with sub-preputial discharge of bacterial balanitis (55.56%), and patchy dry erythema of irritant balanitis (50%). Limitations: Detailed investigations such as fungal culture, herpes serology, real-time polymerase chain reaction and histopathology could not be performed. Conclusion: Certain morphological patterns of balanoposthitis strongly point toward final diagnosis which can help in quick diagnosis and early treatment in resource poor settings, especially in STDs.

A comprehensive review on clinically proven medicinal plants in the treatment of overweight and obesity, with mechanistic insights.

Background and objectives: Obesity has become a global health issue, more precisely, a pandemic throughout the present world due to its high prevalence in the recent era. Increased risk of morbidity and mortality in obese patients can be attributed to its association with the development of different life-threatening conditions. Plants are considered one of the most important sources of bioactive molecules which are used against a wide range of health disorders. This systematic review explores the efficacy as well as the safety profile of commonly used medicinal plants in the management of obesity that may help people to maintain a healthy weight. Methods: This review is based on comprehensive literature searches from PubMed, Science Direct, Scopus, and Google Scholar databases using the keywords- "plants in obesity", "plants used in weight reduction" or keywords that are similar to those. Medicinal plants which have been clinically proven for their anti-obesity effect have only been selected for this study and attempts to investigate beneficial effects and adverse effects along with their mechanism of action have also been taken in this review. Results: A significant reduction of weight in both human and other animals are exhibited by the extracts of Phaseolus vulgaris, green coffee, Yerba Mate, green tea, Gynostemma pentaphyllum, and the combination of Cissus quadrangularis/Irvingia gabonensis. All of those plant extracts seemed to work on different physiological pathways and none of those extracts showed any notable adverse effects in human or animal models. Conclusion: Our review suggests that the discussed medicinal plants are effective in reducing the weight of obese patients without causing notable adverse reactions. Although further study is necessary to confirm their exact molecular mechanism and safety in human use.

Clinical triad with multi-biopsy histopathology as a reliable diagnostic marker of mycetomas: a retrospective review from a tertiary care center.

BACKGROUND: Mycetoma is a neglected tropical infectious disease which runs a prolonged and protracted course. Microbiological confirmation is diagnostic yet unreliable due to poor sensitivity and variable availability of culture facilities in resource poor settings. METHODS: A retrospective review was performed on electronic records (histopathology, microbiology, and radiology) of all patients who underwent skin biopsies with mycetoma as one of the clinical differential diagnoses from year 2016 to 2020. RESULTS: Out of 73 patients biopsied with a differential of mycetoma, 42 fit the clinical triad of swelling-sinuses-granules. After clinical, microbiological, pathological, and radiological correlation, 31 cases were of eumycetoma and seven were of actinomycetoma. Mean patient age was 37.58 ± 13.8 years with a male to female ratio 2.45 : 1 and mean disease duration of 11.31 ± 10.9 years. Histopathological findings revealed fungal hyphae in 18 cases and gram-positive bacteria in six cases. Fungal culture was positive in 13 cases with the three commonest organisms being Madurella mycetomatis in five cases, Fusarium and Aspergillus nidulans in two cases each. X-ray changes of soft tissue, bones, and joints were seen in 25 cases, and "dot-in-circle" sign was seen in eight of nine MRIs. CONCLUSION: Eumycetoma was more common than actinomycetoma in our setup, ratio being 4.43 : 1. A clinical triad of swelling, multiple sinuses and grainy discharge with any one diagnostic support (histopathology/radiology) is sufficient to make a definitive diagnosis of mycetoma in the absence of microbiological identification.

Myths, misconceptions and attitudinal trends among patients with acne.

Background Despite acne being a common dermatological problem, there is a paucity of literature addressing the knowledge, attitude and practice about it. Aims/Objectives To find out what patients know about acne, its cause and treatment, as well as myths, misconceptions and attitude towards it. Methods A cross-sectional, descriptive questionnaire-based study on acne patients at Maharana Bhupal Hospital, RNT Medical College, Udaipur, Rajasthan, India. Results Most (84.8%) patients belonged to the age group of 16-25 years. The majority (63.9%) presented 12 months after the onset of acne. More than half had average knowledge, a positive attitude and good practices, related significantly to gender and education. Limitations A standardized questionnaire suitable for all dialects and regional languages would have yielded more uniform results. Conclusion Study revealed that acne patients still need to acquire accurate, adequate and easily accessible information to seek timely and appropriate treatment, and alleviate their psychological suffering.

Extensive actinomycosis with intracranial and mediastinal involvement: a therapeutic challenge.

Central nervous system (CNS) involvement by actinomycosis is rare, seen in 2%-3% cases. It mostly spreads to CNS by haematogenous route from a distant primary site such as oral cavity, lung, abdomen or pelvis. Direct CNS extension can also occur. It mostly presents as brain abscess, meningoencephalitis, actinomycetoma, subdural empyema and epidural abscess. We report one case of extensive actinomycosis having intra and extraparenchymal CNS, spinal canal, retropharyngeal and mediastinal involvement. Due to such widespread extension and involvement of vital areas, complete surgical debulking was not possible. In addition to therapeutic resistance to conventional antibiotics, repetitive negative cultures posed significant difficulty in the case management.

Investigation of redox mechanism and DNA binding of novel 2-(x-nitrophenyl)-5-nitrobenzimidazole (x = 2, 3 and 4).

The present study describes the investigation of the binding modes of potential anti-cancerous nitrophenyl derivatives of 2-(x-nitrophenyl)-5-nitrobenzimidazole with calf thymus DNA. The -2-(x-nitrophenyl)-5-nitrobenzimidazoles under investigation differ only in position x of nitro group in nitrophenyl substituent relative to benzimidazole moiety leading to 1-NPNB (x = 2), 2-NPNB (x = 3) and 3-NPNB (x = 4). The DFT calculations predicted that derivatives were electrochemically reducible which was then confirmed by cyclic voltammetry. In cyclic voltammetry, the second reversible peak was dependent on first irreversible reduction. This revealed that electrochemical irreversible process was governed by some other process which was then followed by reversible second electron transfer. Thus, ECE (electron transfer leading to coupled chemical reaction followed by another electron transfer process) mechanism was attributed for electrochemical reduction. Experimental results based on UV-Vis spectroscopy vaguely showed intercalation of 1-NPNB, 2-NPNB and 3-NPNB into DNA which was assisted by cyclic voltammetry. However, thermal melting and florescence spectroscopy unambiguously established intercalation for all three compounds. Molecular docking analysis ascertained in pocket stacking of 5-nitrobenzimidazole moiety in 1-NPNB and 2-NPNB while nitro phenyl substitution in 3-NPNB stacks between DNA base pair during intercalation which was in agreement with DFT computed molecular geometry. Therefore, the relative positions of nitro group and 5-nitrobenzimidazole moieties in 2-(x-nitrophenyl)- 5-nitrobenzimidazole influenced the DNA binding pattern of compounds during intercalation. The cytotoxicity of these compounds was comparable to standard drug doxorubicin against both cancerous (MCF-7) and normal (MCF-10A) breast cells which depicts their anti-cancerous potential.

Effect of carbon fiber type on monotonic and fatigue properties of orthopedic grade PEEK.

Carbon-fiber reinforced (CFR) PEEK implants are used in orthopedic applications ranging from fracture fixation plates to spinal fusion cages. Documented implant failures and increasing volume and variety of CFR PEEK implants warrant a clearer understanding of material behavior under monotonic and cyclic loading. To address this issue, we conducted monotonic and fatigue crack propagation (FCP) experiments on orthopedic grade unfilled PEEK and two formulations of CFR PEEK (PAN- and pitch-based carbon fibers). The effect of annealing on FCP behavior was also studied. Under monotonic loading, fiber type had a statistically significant effect on elastic modulus (12.5 ±â€¯1.3 versus 18.5 ±â€¯2.3 GPa, pitch versus PAN CFR PEEK, AVG ±â€¯SD) and on ultimate tensile strength (145 ±â€¯9 versus 192 ±â€¯17 MPa, pitch versus PAN CFR PEEK, AVG ±â€¯SD). Fiber type did not have a significant effect on failure strain. Under cyclic loading, PAN CFR PEEK demonstrated an increased resistance to FCP compared with unfilled and pitch CFR PEEK, and this improvement was enhanced following annealing. Pitch CFR PEEK exhibited FCP behavior similar to unfilled PEEK, and neither material was appreciably affected by annealing. The improvements in monotonic and FCP behavior of PAN CFR PEEK is attributed to a compound effect of inherent fiber properties, increased fiber number for an equivalent wt% reinforcement, and fiber aspect ratio. FCP was shown to proceed via cyclic modes during stable crack growth, which transitioned to static modes (more akin to monotonic fracture) at longer crack lengths. The mechanisms of fatigue crack propagation appear similar between carbon-fiber types.

Design, synthesis, in-vitro thymidine phosphorylase inhibition, in-vivo antiangiogenic and in-silico studies of C-6 substituted dihydropyrimidines.

Thymidine phosphorylase (TP) is an angiogenic enzyme. It plays an important role in angiogenesis, tumour growth, invasion and metastasis. In current research work, we study the effect of structural modification of dihydropyrimidine-2-ones (DHPM-2-ones) on TP inhibition. A series of eighteen new derivatives of 3,4-dihydropyrimidone-2-one were designed and synthesized through the structural modification at C-6 position. All these new derivatives were then assessed for in-vitro inhibition of thymidine phosphorylase (TP) from E. coli. Oxadiazole derivatives 4a-e exhibited excellent TP-inhibition at low micromolar concentration levels better than standard drug 7-deazaxanthine (7-DX). Among all these compounds, 4b was found to be the most potent with IC50 = 1.09 ±â€¯0.004 µM. Anti-angiogenesis potential of representative compounds were also studied in a chorioallantoic membrane (CAM) assay. Here again, compound 4b was found to be the potent anti-angiogenesis compound in a CAM assay. Docking studies were also performed with Molecular Operating Environment (MOE) to further analyse the mode of inhibition of these compounds. Binding mode analysis of the most active inhibitors showed that these are well accommodated into the binding site of enzyme though stable hydrogen bonding and hydrophobic interactions.

Design, synthesis, in vitro Evaluation and docking studies on dihydropyrimidine-based urease inhibitors.

In our previous report, we have identified 3,4-dihydropyrimidine scaffold as promising class of urease inhibitor in a structure based virtual screen (SBVS) experiment. In present study, we attempted to optimize the scaffold by varying C-5 substituent. The elongation of the C-5 chain was achieved by the reaction of C-5 ester with hydrazine leading to C-5 carbohydrazides which were further used as building blocks for the synthesis of fifteen new compounds having diverse moieties. A significantly higher in vitro urease inhibitory activity with IC50 values in submicromolar range was observed for semithiocarbazide derivatives (4a-c, 0.58-0.79µM) and isatin Schiff base derivative 5a (0.23µM). Docking analysis suggests that the synthesized compounds were anchored well in the catalytic site and extending to the entrance of binding pocket and thus restrict the mobility of the flap by interacting with its key amino acid residues. The overall results of urease inhibition have shown that these compounds can be further optimized and developed as lead urease inhibitors.

Microwave-assisted green synthesis of superparamagnetic nanoparticles using fruit peel extracts: surface engineering, T 2 relaxometry, and photodynamic treatment potential.

Superparamagnetic iron oxide nanoparticles (SPIONs) have the potential to be used as multimodal imaging and cancer therapy agents due to their excellent magnetism and ability to generate reactive oxygen species when exposed to light. We report the synthesis of highly biocompatible SPIONs through a facile green approach using fruit peel extracts as the biogenic reductant. This green synthesis protocol involves the stabilization of SPIONs through coordination of different phytochemicals. The SPIONs were functionalized with polyethylene glycol (PEG)-6000 and succinic acid and were extensively characterized by X-ray diffraction analysis, field emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, atomic force microscopy, Rutherford backscattering spectrometry, diffused reflectance spectroscopy, fluorescence emission, Fourier-transform infrared spectroscopy, ultraviolet-visible spectroscopy, and magnetization analysis. The developed SPIONs were found to be stable, almost spherical with a size range of 17-25 nm. They exhibited excellent water dispersibility, colloidal stability, and relatively high R 2 relaxivity (225 mM(-1) s(-1)). Cell viability assay data revealed that PEGylation or carboxylation appears to significantly shield the surface of the particles but does not lead to improved cytocompatibility. A highly significant increase of reactive oxygen species in light-exposed samples was found to play an important role in the photokilling of human cervical epithelial malignant carcinoma (HeLa) cells. The bio-SPIONs developed are highly favorable for various biomedical applications without risking interference from potentially toxic reagents.

Structure based medicinal chemistry-driven strategy to design substituted dihydropyrimidines as potential antileishmanial agents.

In an attempt to explore novel and more potent antileishmanial compounds to diversify the current inhibitors, we pursued a medicinal chemistry-driven strategy to synthesize novel scaffolds with common pharmacophoric features of dihydropyrimidine and chalcone as current investigational antileishmanial compounds. Based on the reported X-ray structure of Pteridine reductase 1 (PTR1) from Leishmania major, we have designed a number of dihydropyrimidine-based derivatives to make specific interactions in PTR1 active site. Our lead compound 8i has shown potent in vitro antileishmanial activity against promastigotes of L. Major and Leishmania donovani with IC50 value of 0.47 µg/ml and 1.5 µg/ml respectively. The excellent in vitro activity conclusively revealed that our lead compound is efficient enough to eradicate both visceral and topical leishmaniasis. In addition, docking analysis and in silico ADMET predictions were also carried out. Predicted molecular properties supported our experimental analysis that these compounds have potential to eradicate both visceral and topical leishmaniasis.