Search

Background & Aims: The mechanism behind the progressive pathological alteration in metabolic dysfunction-associated steatotic liver disease/steatohepatitis (MASLD/MASH)-associated hepatocellular carcinoma (HCC) is poorly understood. In the present study, we investigated the role of the polyol pathway enzyme AKR1B1 in metabolic switching associated with MASLD/MASH and in the progression of HCC., Methods: AKR1B1 expression was estimated in the tissue and plasma of patients with MASLD/MASH, HCC, and HCC with diabetes mellitus. The role of AKR1B1 in metabolic switching in vitro was assessed through media conditioning, lentiviral transfection, and pharmacological probes. A proteomic and metabolomic approach was applied for the in-depth investigation of metabolic pathways. Preclinically, mice were subjected to a high-fructose diet and diethylnitrosamine to investigate the role of AKR1B1 in the hyperglycemia-mediated metabolic switching characteristic of MASLD-HCC., Results: A significant increase in the expression of AKR1B1 was observed in tissue and plasma samples from patients with MASLD/MASH, HCC, and HCC with diabetes mellitus compared to normal samples. Mechanistically, in vitro assays revealed that AKR1B1 modulates the Warburg effect, mitochondrial dynamics, the tricarboxylic acid cycle, and lipogenesis to promote hyperglycemia-mediated MASLD and cancer progression. A pathological increase in the expression of AKR1B1 was observed in experimental MASLD-HCC, and expression was positively correlated with high blood glucose levels. High-fructose diet + diethylnitrosamine-treated animals also exhibited statistically significant elevation of metabolic markers and carcinogenesis markers. AKR1B1 inhibition with epalrestat or NARI-29 inhibited cellular metabolism in in vitro and in vivo models., Conclusions: Pathological AKR1B1 modulates hepatic metabolism to promote MASLD-associated hepatocarcinogenesis. Aldose reductase inhibition modulates the glycolytic pathway to prevent precancerous hepatocyte formation., Impact and Implications: This research work highlights AKR1B1 as a druggable target in metabolic dysfunction-associated steatotic liver disease (MASLD) and hepatocellular carcinoma (HCC), which could provide the basis for the development of new chemotherapeutic agents. Moreover, our results indicate the potential of plasma AKR1B1 levels as a prognostic marker and diagnostic test for MASLD and associated HCC. Additionally, a major observation in this study was that AKR1B1 is associated with the promotion of the Warburg effect in HCC., Competing Interests: The authors of this study declare that they do not have any conflict of interest. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Authors.)

The goal of this study is to find a cure for the masticatory muscle disease known as hemimasticatory spasm (HMS). This retrospective investigation intends to find a more efficient therapeutic approach for HMS patients by examining the clinical effectiveness of masseteric nerve avulsion performed on HMS using a temporomandibular arthroscope. A clinical study was piloted where the subjects were treated for masseter nerve avulsion by TMJ arthroscopy. The follow-up was done till 2 years, and the subjects were evaluated for the various characteristics like difficulties, masticatory abilities, and various sounds at the joint for the various functions of the joint. The diagnosis was done using the electrophysiological electromyogram (EMG) at the designated time intervals. There was a complete remission in all the subjects. The masseter nerve avulsion was effective since the scores lowered. Within 3 years of the operation, electrophysiological EMG depicted no discharge potential with a high frequency, and the total efficiency when paired with the clinical effectiveness was deemed acceptable. The maximal masseter power between the treated and nontreated sides was comparable. The mastication, on comparing, was also as effective as the normal side; however, lower mastication was noted in the first year. The avulsed nerve tissues lacked any apparent demyelination. Masseteric nerve avulsion with temporomandibular arthroscope assistance provided acceptable and stable total effectiveness for the intervention of the hemimasticatory spasm. While the strength of the muscle of the afflicted side was only marginally reduced, its masticatory effectiveness was optimally preserved., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Pharmacy and Bioallied Sciences.)

Introduction: The palatal rugae may alter their shape based on the various physical pressures that they had to endure. This study's objective is to assess the various alterations in the palatal rugae parameters among the complete denture wearers., Materials and Procedures: Forty subjects in all were chosen for the study. The control group interventional groups had an equal number of participants who were further equally distributed based on gender. For all of the participants, mucostatic maxillary alginate imprints were taken, and gypsum castings were created. They were called at the scheduled intervals of 2, 6, and 12 months following the treatment. The models used during those recalls and all of the palatal rugae were examined under a microscope for quantity, length, form, orientation, and unifications. The unpaired t-test was used to statistically examine palatal rugae alterations., Results: Following the wear of the dentures, the experimental group's primary, secondary, and fragmented rugae all gradually shrank in length. In terms of statistics, the alteration solely affected primary rugae and was significant ( P < 0.001). After a year of wearing dentures, a minimal change in rugae's form was noticed in the denture groups, but it was statistically not substantial ( P > 0.05)., Conclusion: Due to the prolonged mechanical stress the dentures placed on the palatal rugae, complete denture users saw a significant reduction in the length of their primary rugae. Rugae number, orientation, and unification were among the other criteria that did not change during the course of the study. Analysis of the palatal rugae may not be useful in identifying people wearing full dentures. However, in forensic investigations, rugae may act as an adjunct to other methods like fingerprints and DNA analysis., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Pharmacy and Bioallied Sciences.)

Introduction: Opioid may cause undue risk after surgical procedures like orthognathic surgeries. The present study was aimed to determine how the preoperative administration of oral montelukast affected the degree of postoperative discomfort following bimaxillary orthognathic surgery (BOS)., Methodology: This study included all skeletal class III subjects scheduled for BOS. The participants were split into placebo and montelukast groups at random. Every patient received a 10-mL serving of apple juice an hour prior to the surgery; however, for the intervention group, a montelukast 10 mg pill was dissolved in the juice. The same surgical team and general anesthetic guidelines were used for all procedures. The visual analog scale (VAS) was used to calculate postoperative pain at designated intervals. The significance level for the statistical analysis was determined using the Statistical Package for the Social Sciences (SPSS) version 23., Results: The control subjects had a higher level of pain at all the intervals than the intended drug test group. Also, the control group needed more analgesics than the test group. There was one observation made that the length of the surgery had an impact on the postoperative pain., Conclusion: Preoperative montelukast medication may be useful in minimizing postoperative discomfort following bimaxillary orthognathic surgery. More research is required for greater relevance., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Pharmacy and Bioallied Sciences.)

In forensic, odontologic, genetic, and anthropological aspects, odontometric and osteologic features have long been a valuable source. The goal of this research was to correlate both the osteologic and odontometric characteristics to determine the most accurate approach for determining gender. A retrospective study involving 1000 adults, with equal gender distribution, was carried out utilizing digital panoramic radiography. The archives were searched for radiographic images of the subjects that were procured for the various procedures that ranged from implantations to rehabilitations. The measurement process was carried out with Image-Pro. There was a noticeable gender difference in the mesodistal breadth, which ranged from 17 to 47. Asymmetry of the lower jaw was considerable in both genders, as was gender variance in osseologic characteristics including ramus diameter and gonial angle. The two groups of attributes exhibited a substantial positive predictive value and thus can be used indetermining gender., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Pharmacy and Bioallied Sciences.)

The synthesis of multiply substituted acenes is still a relevant research problem, considering their applications and future potential. Here we present an elegant synthetic protocol to afford tetra-peri-substituted naphthalene and tetracene from their tetrahalo derivatives by a Pd(0)-catalyzed C-C cross-coupling method in a single step. The newly synthesized tetracenes were characterized by NMR, HRMS, UV-vis spectrophotometry, and single-crystal X-ray diffraction (SCXRD). In addition, the first systematic computational study of the effect of chalcogenophenyl substitutions on the chiroptical properties of twistacenes was reported here. The gas phase computational studies using density functional theory (DFT) on a series of chalcogenophene-substituted tetracenes revealed that their chiroptical activity could be systematically increased via the atomistic tuning of peripheral substituents.

Identifying the target linking inflammation and oxidative stress to aggravate the disease progression will help to prevent colitis associated carcinogenesis. Since AKR1B1 overexpression is observed in inflammatory diseases and various cancers, we have investigated the role of AKR1B1 in colitis-associated colon carcinogenesis with the aid of epalrestat and its potent analogue NARI-29 (investigational molecule) as pharmacological probes. A TNF-α inducible NF-κB reporter cell line (GloResponse™ NF-κB-RE-luc2P HEK293) and dextran sodium sulfate (DSS) and 1,2 dimethyl hydrazine (DMH))-induced mouse model was used to investigate our hypothesis in vitro and in vivo. Clinically, an increased expression of AKR1B1 was observed in patients with ulcerative colitis. Our in vitro and in vivo findings suggest that the AKR1B1 modulated inflammation and ROS generation for the progression of colitis to colon cancer. AKR1B1 overexpression was observed in DSS + DMH-treated mice colons. Moreover, we could observe histopathological changes like immune cell infiltration, aberrant crypt foci, and tumour formation in DC groups. Mechanistically, we have witnessed modulation of the IKK/IκB/NF-κB and Akt/FOXO-3a/DR axis, increased inflammatory cytokines, increased expression of proliferative markers, Ki-67 and PCNA, and accumulation of β-catenin in the colon epithelium. However, pharmacological inhibition of AKR1B1 using NARI-29 or EPS has reversed the clinical, histopathological, and molecular alterations induced by DSS + DMH, confirming the obvious role of AKR1B1 in the promotion of colitis-associated carcinogenesis. In conclusion, our findings suggest that AKR1B1 targeted therapy could be a promising strategy for preventing CA-CRC and NARI-29 could be developed as a potent AKR1B1 inhibitor., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Tamoxifen and toremifene are two selective estrogen receptor modulators (SERMs) commonly used to treat breast cancer in women. Toremifene is well-known as a triphenylethylene derivative. Carboxy toremifene is a common metabolite of toremifene and tamoxifen. Since 2005, the World Anti-Doping Agency (WADA) has banned the SERMs category during in and out of competition. These substances are in the S4 category in the WADA prohibited list as "agents with anti-oestrogenic activity." However, there is no commercially accessible carboxy toremifene reference material in the market. This research highlights the novel synthetic procedure, the development of a carboxy toremifene HPLC method, and validation, along with detailed characterization using advanced analytical techniques using 1 H NMR, HRMS, FT-IR-ATR and UV-visible spectroscopy. RP-HPLC-DAD method was developed and validated to assess the purity of carboxy toremifene. Developed reference material has shown 100% purity. Therefore, we recommend that this synthesized carboxy toremifene may be used as reference material to strengthen the WADA-accredited lab to maintain a clean sports mission during sports competitions., (© 2022 John Wiley & Sons Ltd.)

Ethylmorphine is permitted internationally for therapeutic purposes where morphine is not indicated across the globe. Nor-ethylmorphine a major metabolite of ethylmorphine. To differentiate the intake of morphine from ethylmorphine, nor-ethylmorphine stable reference material is desirable. There is no available commercial source and no data for reference material context for this substance. Therefore, nor-ethylmorphine HCl was synthesized and characterized, and purity and potency were assessed using nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HRMS), Fourier transform infrared spectroscopy (FT-IR), thermogravimetry (TGA), and high-performance liquid chromatography (HPLC). Purity and potency were found to be 98.29% and 96.40%, respectively, providing a fit for purpose reference material for doping control analysis in sports., (© 2021 John Wiley & Sons, Ltd.)

Prenylamine was initially used for the treatment of angina pectoris and later on withdrawn from the market in 1988 due to cardiac arrhythmias concern. The major phase I metabolite of prenylamine is p-hydroxy prenylamine that has a chiral center in the structure. Even though p-hydroxy prenylamine was synthesized earlier, it lacked complete analytical developments for chiral high-performance liquid chromatography (HPLC) separation. However, p-hydroxy prenylamine reference material is not commercially available. The innovation of this manuscript is the development and validation of a chiral HPLC separation method and more extensive characterization of the reference material than previously reported method. Therefore, it was hypothesized to develop and validate normal phase HPLC method for p-hydroxy prenylamine reference material. p-Hydroxy prenylamine was synthesized in two batches and characterized successfully using 13 C NMR, 1 H NMR, high-resolution mass spectrometry (HRMS), Fourier transform infrared spectroscopy (FT-IR), and thermogravimetric analysis (TGA). A normal phase chiral HPLC method was developed to analyze the p-hydroxy prenylamine purity. Separation of the p-hydroxy prenylamine enantiomers were achieved using ultra-high-performance liquid chromatography (UHPLC) on a ChiralCel ODH column at wavelength of 220 nm. The developed method was validated in terms of its linearity, accuracy, precision, and robustness for purification, purity assessment, and stability studies. Proton and carbon peaks were confirmed by nuclear magnetic resonance (NMR) analysis. Functional groups were confirmed by FT-IR. Loss on drying was 0.3% and 0.6% for Batches 1 and 2, respectively. The purity of the developed reference material for Batches 1 and 2 was found to be 99.59% and 100%, respectively. Therefore, the synthesized batches of p-hydroxy prenylamine can be used in dope testing as reference material., (© 2021 John Wiley & Sons, Ltd.)

Ethnopharmacological Relevance: Cleome species in particular (C. gynandra Linn, C. viscosa Linn, C. rutidosperma DC, C. felina Linn.), commonly known as spider flowers, belong to the genus of flowering plants in Cleomaceae family. Found primarily in the African countries (Kenya, Tanzania, Egypt, South Africa, and Nigeria), Asian countries (India and Afghanistan), European countries (Italy), and also in other countries like Brazil and Austria. These plants are commonly cultivated as a vegetable crop for their nutritional benefits, and the leaves are widely consumed for their health-promoting effects. The different parts of the plants, such as leaves, seeds, flowers, and roots, are used to treat acute and chronic inflammatory disorders, hepatotoxicity, malaria, fungal diseases, and cancer., Aim of the Study: Detailed investigations in underlining the molecular mechanisms and their wide variety of effects in treating various diseases remain ambiguous. The review focuses on an in-depth discussion of studies targeting phytochemistry and polypharmacology. Thus, the review aims to recapitulate the therapeutic potential of the components of Cleome involved in the treatment of a wide variety of ailments from ancient times were collected and presented along with strategies aiming for future studies., Materials and Methods: The information provided is collected from several scientific databases (PubMed, Elsevier, ScienceDirect) and traditional medicine books, and other professional websites., Results and Conclusion: Investigations and current evidence revealed that the different chemical constituents present in cleome species possess various health-promoting effects along with the aerial parts showing promising traditional uses in traditional healing and culinary. An explorative survey in the current review highlights the traditional healing effects along with a broad scope of studies that can be performed in the future., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background and Purpose- Acetylsalicylic acid and clopidogrel are the 2 main antithrombotic drugs for secondary prevention in patients with ischemic stroke (IS) without indication for anticoagulation. Because of their limited efficacy and potential side effects, novel antiplatelet agents are urgently needed. Cilostazol, a specific phosphodiesterase (PDE)-3 inhibitor, protected from IS in clinical studies comprising mainly Asian populations. Nevertheless, the detailed mechanistic role of PDE-3 inhibitors in IS pathophysiology is hardly understood. In this project, we analyzed the efficacy and pathophysiologic mechanisms of a novel and only recently described PDE-3 inhibitor (substance V) in a mouse model of focal cerebral ischemia. Methods- Focal cerebral ischemia was induced by transient middle cerebral artery occlusion in 6- to 8-week-old male C57Bl/6 wild-type mice receiving substance V or vehicle 1 hour after ischemia induction. Infarct volumes and functional outcomes were assessed between day 1 and day 7, and findings were validated by magnetic resonance imaging. Blood-brain barrier damage, as well as the extent of local inflammatory response and cell death, was determined. Results- Inhibition of PDE-3 by pharmacological blockade with substance V significantly reduced infarct volumes and improved neurological outcome on day 1 and 7 after experimental cerebral ischemia. Reduced blood-brain barrier damage, attenuated brain tissue inflammation, and decreased local cell death could be identified as potential mechanisms. PDE-3 inhibitor treatment did neither increase the number of intracerebral hemorrhages nor affect platelet function. Conclusions- The novel PDE-3 inhibitor substance V protected mice from IS independent from platelet function. Pharmaceutical inactivation of PDE-3 might become a promising therapeutic approach to combat IS via inhibition of thromboinflammatory mechanisms and stabilization of the blood-brain barrier.

Background: Alkynes are fundamental building blocks in synthetic chemistry with high pharmaceutical applications. Among the bioactive acetylenic molecules, propargylic alcohol is most important as almost all the marketed drugs contains quaternary centered propargylic alcohol functionality., Objective: In this study we have synthesised and evaluated 3-hydroxy-3-ethynylindolin-2-one derivatives for in vitro cytotoxic activity., Method: An expeditious method for direct alkynylation of isatins (ketones) has been developed using tetrabutylammonium fluoride (TBAF) as a catalyst in THF solvent at room temperature under metal-free conditions. Furthermore, this method is an economically viable process that also compliments green aspects like being a ligand/metal free process under ambient conditions. This reaction tolerated a wide range of substrates with good to excellent yields (80-94%)., Results: The results showed that the synthesized compounds (4m, 4n and 4p) has the ability to inhibit Akt kinase activity with IC50 values ranging from 7.7 to 9.8 µM., Conclusion: All the 3-hydroxy-3-ethynylindolin-2-one derivatives were subjected for in vitro cytotoxic activity on five different cancer cell lines. Further, the synthesized compounds (4m, 4n and 4p) were evaluated for their ability to inhibit Akt kinase activity and exhibited good inhibition with IC50 values ranging from 7.7 to 9.8 µM.., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)