REVIEW_ARTICLE Background: Diabetes mellitus, a multifaceted metabolic disorder with diverse etiologies, has remained a significant global health concern, imposing a substantial burden on healthcare systems.  Objectives: This review aims to explore contemporary advancements in diabetes research, shedding light on recent breakthroughs and their potential impact. Methods: A thorough examination of current literature was conducted to identify critical areas in diabetes research. Precision medicine, innovative therapies, biomarker discovery, and technology integration, including artificial intelligence (AI), in diabetes care were investigated to provide a comprehensive overview. Results: The review highlights the emergence of precision medicine as a promising avenue in diabetes research, emphasizing tailored therapeutic approaches based on individual patient characteristics. Innovative therapies, such as gene therapies and advanced pharmacological interventions, present novel strategies for effective diabetes management. Biomarker discovery is a key focus, which helps identify reliable indicators for early diagnosis and personalized treatment strategies. Incorporating technology, including continuous glucose monitoring and insulin delivery systems, reflects a paradigm shift in diabetes care. Conclusion: This review underscores the dynamic landscape of diabetes research, emphasizing the crucial role of precision medicine, innovative therapies, biomarker discovery, and technology integration in shaping future directions. The evolving role of AI in diabetes care signifies a transformative potential for personalized, data-driven interventions. By providing insights into contemporary advancements, this review contributes to the ongoing efforts to develop more effective prevention and management strategies for diabetes, addressing the pressing global health challenge posed by this complex metabolic disorder. http://pbr.mazums.ac.ir/article-1-583-en.pdf 2024-08-08 167 178 10.32598/PBR.10.3.1240.1 Diabetes mellitus (DM) Biomarkers Precision medicine Innovative treatment approaches Telemedicine Nithesh Kumar G knitesh913@gmail.com 1 Department of Pharmacology, Sri Adichunchanagiri College of Pharmacy, Adichunchanagiri University, Nagamangala, India AUTHOR https://orcid.org/0009-0001-3032-2292 Bharathi D R pharmacology.saccp@accp.co.in 2 Department of Pharmacology, Sri Adichunchanagiri College of Pharmacy, Adichunchanagiri University, Nagamangala, India AUTHOR https://orcid.org/0000-0002-8153-2839 Chandan K chandankumar@accp.co.in 3 Department of Pharmacology, Sri Adichunchanagiri College of Pharmacy, Adichunchanagiri University, Nagamangala, India AUTHOR https://orcid.org/0000-0002-3092-500X Jayanth B M jayanthbm5@gmail.com 4 Department of Pharmacology, Sri Adichunchanagiri College of Pharmacy, Adichunchanagiri University, Nagamangala, India AUTHOR Syed Sagheer Ahmed sysaha6835@gmail.com 5 Department of Pharmacology, Sri Adichunchanagiri College of Pharmacy, Adichunchanagiri University, Nagamangala, India AUTHOR https://orcid.org/0000-0001-9817-9747

ORIGINAL_ARTICLE Background: Aging with the gradual loss of organ functions leads to extensive complications. As the world’s elderly population is increasing.  Objectives: We aimed to investigate the effect of Glycyrrhiza glabra (GLY) on biochemical factors, telomerase content, and antioxidant levels in aged tissues. Methods: Thirty aged rats were divided into 3 groups: AG or aging group (control), AG-low GLY (150 mg/kg), and AG-high GLY (300 mg/kg). GLY extract gavage was carried out for 2 weeks. Eventually, the heart, liver, hippocampus, and right kidney tissues were removed to evaluate their antioxidant levels. The serum samples were used to measure the level of aminotransferase (AST), alanine aminotransferase (ALT), urea, creatinine, and telomerase enzyme activity.  Results: The results indicated that administering high dose GLY extract reduced oxidative stress notably in the tissues and blood serum. There was a remarkable decline in the urea, creatinine levels, and ALT in the aged group receiving a high dose of GLY, but the change in AST was insignificant. Receiving GLY extract in low and high doses elevated the telomerase enzyme activity remarkably. Conclusion: The current study supports that administering GLY extract (300 mg/kg) can effectively ameliorate aging-related disturbances.  http://pbr.mazums.ac.ir/article-1-584-en.pdf 2024-08-08 179 190 10.32598/PBR.10.3.562.5 Aging Glycyrrhiza glabra (GLY) Oxidative stress Telomerase Shabnam Mohammadi mohammadish@mums.ac.ir 1 Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. AUTHOR https://orcid.org/0000-0002-2352-286X Negar Ostad-Rahimi n.ostadrahimi74@gmail.com 2 Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. AUTHOR https://orcid.org/0000-0001-6110-0425 Abolfazl Rezaei shabnammhmmd@yahoo.com 3 Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. AUTHOR https://orcid.org/0000-0002-0259-5103

ORIGINAL_ARTICLE Background: In the spectrum of neurodegenerative conditions, Alzheimer disease (AD) stands out as the predominant contributor to dementia and behavioral alterations. Cholinesterase inhibitors (ChE-Is) represent the primary pharmaceutical category currently endorsed for addressing AD.  Objectives: This investigation assessed the potential of selected test compounds to inhibit cholinesterase, specifically targeting acetylcholinesterase (AChE), through in silico approaches. Methods: In this investigation, five test compounds—oxypertine, cinitapride, niaprazine, fenoverine, and clebopride—were identified and selected based on their electroshape resemblance to donepezil, utilizing the SwissSimilarity web server. Molecules with shapes similar to donepezil can fit into the AChE active site more snugly, facilitating similar interactions. AChE (PDB ID: 6U34) was sourced from the RCSB Protein Data Bank (PDB) and prepared for molecular docking with Discovery Studio 2020 software. Molecular docking was executed using PyRx, while visualization was performed with Discovery Studio 2020 software. Furthermore, the physicochemical properties (adhering to Lipinski’s rule of five), drug-likeness, and various parameters, encompassing absorption, distribution, metabolism, elimination, and toxicity (ADMET) profiles of the test compounds were scrutinized utilizing the SwissADME server. These findings were juxtaposed with those of donepezil, the standard drug. Results: The docking scores revealed that fenoverine (-10.40 kcal/mol) exhibits greater potency against 6U34 compared to donepezil (-10.30 kcal/mol), while clebopride, cinitapride, niaprazine, and oxypertine (-9.50, -9.40, -9.20, and -9.10 kcal/mol, respectively) demonstrated lower potency against 6U34 relative to donepezil. All compounds adhered to Lipinski’s drug-likeness rules and displayed promising ADMET profiles suitable for therapeutic applications as ChE-Is. Conclusion: Based on molecular docking and pharmacological parameters, fenoverine is a suitable alternative to donepezil. However, further studies using in vivo methods and other techniques are recommended to validate the results of this study. http://pbr.mazums.ac.ir/article-1-619-en.pdf 2024-08-08 191 202 10.32598/PBR.10.3.1065.3 Acetylcholine Acetylcholinesterase (AChE) Cholinesterase inhibitors Donepezil Nathaniel Ohiemi Amedu amedu.nathaniel@adelekeuniversity.edu.ng 1 Department of Anatomy, Faculty of Basic Medical Sciences, Adeleke University, Ede, Nigeria. AUTHOR https://orcid.org/0000-0002-8490-2292 Michael Olim Obu michaelolim7@gmail.com 2 Department of Anatomy, College of Basic Medical Sciences, Chrisland University, Abeokuta, Nigeria. AUTHOR

ORIGINAL_ARTICLE Background: Janus kinase (JAK) inhibitors are recently launched treatments with a new mechanism of action, so their safety needs to be verified through long-term usage. Objectives: This study aimed to determine the clinical characteristics of JAK inhibitor-related adverse events (AEs) in a real-world setting, using data from the Japanese adverse drug event report (JADER) database. Methods: AEs are defined using the preferred terms from the dictionary of medical terms for regulatory agencies and include pneumonia, herpes zoster (HZ), hematopoietic erythropenia, hematopoietic leukopenia, hematopoietic thrombocytopenia, liver disorder, renal impairment, interstitial lung disease (ILD), cardiac failure, embolic and thrombotic events, gastrointestinal perforation, and hyperglycemia. Adjusted reported odds ratios (ROR) are used to assess disproportionality in the pharmacovigilance data, and time-to-onset analysis is performed using Weibull shape parameters. Results: The JADER database contained 823662 reports published between April 2004 and March 2023. Pneumonia and HZ are associated with all JAK inhibitors except filgotinib. Adjusted RORs for pneumonia with peficitinib, tofacitinib, baricitinib, ruxolitinib, filgotinib, and upadacitinib are 4.4 (95% CI, 3.36%, 5.75%), 6.93 (95% CI, 6.18%, 7.77%), 6.51 (95% CI, 5.52%, 7.67%), 3.3 (95% CI, 2.76%, 3.95%), 4.39 (95% CI, 2.55%, 7.58%), and 6.11 (95% CI, 4.53%, 8.23%), respectively. Adjusted RORs for HZ with peficitinib, tofacitinib, baricitinib, ruxolitinib, and upadacitinib are 8.94 (95% CI, 5.69%, 14.05%), 31.82 (95% CI, 27.58%, 36.71%), 34.96 (95% CI, 28.92%, 42.26%), 5.24 (95% CI, 3.57%, 7.7%), and 33.19 (95% CI, 23.81%, 46.27%), respectively. The median time-to-onset of pneumonia and HZ with JAK inhibitor usage ranged from 2 to 6 months and 4 to 7 months, respectively. Conclusion: We demonstrated the potential risks of JAK inhibitor use with real-world data. The present analysis shows that patients receiving peficitinib, tofacitinib, baricitinib, ruxolitinib, filgotinib, or upadacitinib should be closely monitored for AEs. The most common AEs associated with JAK inhibitors were pneumonia and HZ.   http://pbr.mazums.ac.ir/article-1-560-en.pdf 2024-08-08 203 228 10.32598/PBR.10.3.1207.3 Pharmacovigilance Tofacitinib Janus kinase (JAK) Pneumonia Herpes zoster (HZ) Hideyuki Tanaka mubannsou@gmail.com 1 Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan. AUTHOR https://orcid.org/0000-0000-0000-0000 Mika Maezawa kykm1994@gmail.com 2 Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan. AUTHOR https://orcid.org/0000-0002-9166-1351 Satoshi Nakao nakao.satoshi.442@m.kyushu-u.ac.jp 3 Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan. AUTHOR https://orcid.org/0000-0001-7413-2637 Koumi Miyasaka 195116@gifu-pu.ac.jp 4 Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan. AUTHOR https://orcid.org/0000-0000-0000-0000 Sakiko Hirofuji 195107@gifu-pu.ac.jp 5 Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan. AUTHOR https://orcid.org/0000-0000-0000-0000 Moe Yamashita 205116@gifu-pu.ac.jp 6 Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan. AUTHOR https://orcid.org/0000-0000-0000-0000 Kensuke Matsui 205102@gifu-pu.ac.jp 7 Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan. AUTHOR https://orcid.org/0000-0000-0000-0000 Nanaka Ichihara 205008@gifu-pu.ac.jp 8 Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan. AUTHOR https://orcid.org/0000-0000-0000-0000 Yuka Nokura 205081@gifu-pu.ac.jp 9 Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan. AUTHOR https://orcid.org/0000-0000-0000-0000 Mari Iwata m-iwata@kifune.info 10 Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan. AUTHOR https://orcid.org/0000-0000-0000-0000 Mayumi Kitamura m-kitamura@alice.asahi-u.ac.jp 11 Department of Nursing, School of Health Science, Asahi University, Gifu, Japan. AUTHOR https://orcid.org/0000-0000-0000-0000 Megumi Horibe m-horibe0814@alice.asahi-u.ac.jp 12 Department of Nursing, School of Health Science, Asahi University, Gifu, Japan. AUTHOR https://orcid.org/0000-0000-0000-0000 Hirofumi Tamaki tamaki-hi@gifu-pu.ac.jp 13 Laboratory of Community Pharmacy, Gifu Pharmaceutical University, Gifu, Japan. AUTHOR https://orcid.org/0000-0002-4543-1176 Kazuhiro Iguchi iguchi@gifu-pu.ac.jp 14 Laboratory of Community Pharmacy, Gifu Pharmaceutical University, Gifu, Japan. AUTHOR https://orcid.org/0000-0000-0000-0000 Mitsuhiro Nakamura mnakamura@gifu-pu.ac.jp 15 Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan. AUTHOR https://orcid.org/0000-0002-5062-5522

ORIGINAL_ARTICLE Background: Nanostructured lipid carriers (NLCs) are emerging as the second generation of lipid nanoparticles to solve the shortcomings of the first generation (structured lipid carriers). Terbinafine hydrochloride is used to treat various fungal skin diseases.  Objectives: The study’s main objective was to study the drug release and permeation between NLC and NLC-based gel formulation to select the better one.  Methods: A central composite face-cantered (α=1) design with two components (the amount of liquid lipid and the homogenization speed) and 13 runs were used through Design-Expert® software (version 7.1.5). Terbinafine hydrochloride-loaded NLC (TH_NLC) was produced by using the hot-homogenization technique. Fourier transform infrared study was done to determine drug excipients’ compatibility. Dynamic light scattering (DLS) was employed to determine particle size. Utilizing scanning electron microscopy (SEM), the morphology and shape of the TH_NLC formulation were examined. The hydrogel was filled with the optimized products chosen by point prediction in design expert software. These products were assessed by their pH, spreadability, viscosity, homogeneity, extrudability, and drug content. The in vitro drug release study and the ex vivo permeation investigation for the optimized TH_NLCopt and TH_NLCopt gel formulation were carried out using Franz diffusion cells Results: The formulation contains nanoscale particles, as evidenced by the size range of the particles (17.57 to 329.4 nm). Entrapment efficiency was 60.95% and 98% for TH_NLCopt TH_NLCopt gel, respectively. Within 7 hours, 96.35% and 83.37% of the drug were released from optimized NLC and NLC-based gel, respectively. The amount of drug that had penetrated the skin in 7 hours ranged from 54.19% to 31.16%, with a retention range of 22.46% to 61.87%.  Conclusion: The topical delivery of the TH_NLC-based gel system is quite promising.   http://pbr.mazums.ac.ir/article-1-606-en.pdf 2024-08-08 229 246 10.32598/PBR.10.3.1286.11 Lipid nanoparticles Terbinafine Dynamic light scattering (DLS) Spectroscopy Fourier transform infrared Nanoparticles Hydrogels Gopa Roy Biswas goparoy2020@gmail.com 1 Department of Pharmaceutics, School of Pharmacy, Techno India University, Kolkata, India. AUTHOR Soumik Patra soumikpatra1520@gmail.com 2 Department of Pharmaceutics, School of Pharmacy, Seacom Skills University, Bolpur, India. AUTHOR https://orcid.org/0009-0001-3212-6252 Pritam Dutta pritamgnipst1721@gmail.com 3 Department of Pharmaceutics, School of Pharmacy, Neotia University, Kolkata, India. AUTHOR https://orcid.org//0009-0008-6635-5011 Ritu Khanra ritukhanra@yahoo.co.in 4 Department of Pharmaceutical Technology, JIS University, Kolkata, India. AUTHOR https://orcid.org/0000-0002-0208-846X

ORIGINAL_ARTICLE Background: Assessing the characteristics of patients with COVID-19 considerably helps in the timely detection of infected patients, thus reducing the prevalence of COVID-19 and its mortality.  Objectives: This study aims to investigate the demographic, clinical, and laboratory characteristics of patients with COVID-19 admitted to a hospital in Khorramabad City, western Iran, and to find the factors associated with death from COVID-19. Methods: This is a descriptive-analytical study with a cross-sectional design. The data of all patients with COVID-19 hospitalized in Shahadaye Ashayer Hospital in the mid-year of 2021 were examined (n=555). A researcher-made checklist was used to extract patient information, including demographic data, history of smoking, clinical symptoms, history of underlying diseases, and laboratory findings. Then, they were analyzed in SPSS software, version 19, using descriptive statistics, as well as independent t-test and chi-square test. The significance level was set at 0.05. Results: There were 481 recovered cases (86.7%) and 74 deceased cases (13.3%). The mean age of deceased patients was significantly higher than that of the deceased ones (77.18±9.46 vs 58.49±13.25 years). There was also a significant difference between recovered and deceased patients in terms of marital status (P=0.001), occupation (P=0.001), and history of smoking (P=0.002). Shortness of breath (74.2%), dry cough (63.2%), nausea/vomiting (56.6%), and anorexia (57.2%) were the most prevalent clinical symptoms in patients with COVID-19. The most common underlying diseases were hypertension (15%) and diabetes (9.5%). The difference between the deceased and recovered groups was significant in terms of WBC count, neutrophil percentage, creatinine, and potassium levels, where the deceased patients had higher values in these variables.  Conclusion: People who died from COVID-19 in Khorramabad City were old, married, and unemployed with underlying diseases and higher WBC count, neutrophil percentage, and creatinine and potassium levels. http://pbr.mazums.ac.ir/article-1-617-en.pdf 2024-08-08 247 256 10.32598/PBR.10.3.1300.1 COVID-19 Epidemiology Mortality Social determinants of health Parastoo Baharvand drbaharvand.lums@gmail.com 1 Department of Social Medicine, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran. AUTHOR https://orcid.org/0000-0002-0350-7312 Zahra Vaez drvaezzahra@gmail.com 2 Department of Social Medicine, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran. AUTHOR

ORIGINAL_ARTICLE Background: Uterine fibroids are the most frequently diagnosed tumors of the female reproductive system and the primary reason for hysterectomy. Tetrapleura tetraptera stem bark is traditionally used to treat this condition.  Objectives: To assess the antifibroid activity of the ethanol stem bark extract of T. tetraptera in Sprague-Dawley rats.  Methods: An acute toxicity test was performed to determine the extract’s safety level. Antifibroid activity was evaluated with monosodium glutamate (MSG) administration to rats daily for 30 days and then with concurrent graded doses of the extract (preventive method). A second group of rats were given MSG for 30 days to induce fibroid formation, after which the extract was administered in graded doses for another 30 days (curative method). Biochemical analysis of blood serum was done, and total cholesterol, protein, and estradiol levels were assessed. Histopathological analysis of the uterus was carried out. Major bioactive polyphenolic constituents were identified by high-performance liquid chromatography (HPLC).  Results: The extract exhibited no mortality even at 5000 mg/kg. MSG significantly elevated (P≤0.05) serum cholesterol and estradiol levels in the rats; extract administration inhibited the rise in these parameters, both in the preventive and curative experiments. Histopathology assessment of rat uterus given the extract revealed a reduction in fibroid cells induced by MSG. HPLC analysis identified umbelliferone, piperazine, aridanin, and naringenin as the major phenolic compounds in the extract.  Conclusion: This research’s results support the plant’s antifibroid potential.  http://pbr.mazums.ac.ir/article-1-624-en.pdf 2024-08-08 257 268 10.32598/PBR.10.3.1110.2 Tetrapleura tetraptera Fibroid High-performance liquid chromatography (HPLC) Biochemical Histopathology Rose Osarieme Imade rose.jesuorobo@uniben.edu 1 Department of Pharmacognosy, Faculty of Pharmacy, University of Benin, Benin, Nigeria. AUTHOR https://orcid.org/0000-0001-7252-6392 Buniyamin Adesina Ayinde baayinde@uniben.edu 2 Department of Pharmacognosy, Faculty of Pharmacy, University of Benin, Benin, Nigeria. AUTHOR https://orcid.org/0000-0002-4259-528X Chinaza Esther Onyebuchi buchichinaza@gmail.com 3 Department of Pharmacognosy, Faculty of Pharmacy, University of Benin, Benin, Nigeria. AUTHOR Ekene Victor Asoya ekene.asoya@lifesci.uniben.edu 4 Department of Medical Biochemistry, School of Basic Medical Science, University of Benin, Benin, Nigeria. AUTHOR https://orcid.org/0000-0001-9165-5958

CASE_STUDY Background: Various atypical antipsychotics have been associated with peripheral edema. The exact mechanism of creating edema is not clear yet.  Case Report: A 55-year-old woman with schizophrenia developed pedal edema after taking risperidone, which resolved after discontinuation. However, her symptoms returned when risperidone was restarted. Switching to aripiprazole resolved her edema, with a reduction in dosage preventing further swelling. No edema-related side effects were observed during a 6-month follow-up period. Conclusion: Therefore, it would be recommended that patients, especially those receiving high doses of aripiprazole or risperidone, should be monitored for these side effects. Despite the very low incidence of edema due to the aripiprazole administration, the probable occurrence of this adverse effect should always be considered by psychiatrists, as it may affect patients’ compliance with the prescription. In our case, the reappearance of edema is strong evidence indicating risperidone and aripiprazole cause the swelling.   http://pbr.mazums.ac.ir/article-1-635-en.pdf 2024-08-08 269 274 10.32598/PBR.10.3.1323.1 Edema Risperidone Aripiprazole Schizophrenia Mojtaba Ahmadi mojtaba.ahmadi12@gmail.com 1 Psychiatry and Behavioral Sciences Research Center, Addiction Institute, Mazandaran University of Medical Sciences, Sari, Iran. AUTHOR https://orcid.org/0009-0003-9841-1464 Seyed Hamzeh Hosseini shhosseini@mazums.ac.ir 2 Psychiatry and Behavioral Sciences Research Center, Addiction Institute, Mazandaran University of Medical Sciences, Sari, Iran. AUTHOR https://orcid.org/0000-0002-0987-4295