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Amr J Halawani,1 Abdullah A Mobarki,2 Ali H Arjan,3 Muhammad Saboor,2 Hassan A Hamali,2 Gasim Dobie,2 Khalaf F Alsharif4 1Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia; 2Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia; 3Department of Laboratory and Blood Bank, King Fahad Central Hospital, Ministry of Health, Jazan, Saudi Arabia; 4Department of Clinical Laboratory Science, College of Applied Medical Sciences, Taif University, Taif, Saudi ArabiaCorrespondence: Amr J Halawani, Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia, Email ajjhalawani@uqu.edu.saPurpose: Sickle cell disease (SCD) and thalassemia are common inherited blood disorders in Saudi Arabia, especially in Jazan Province. Patients with these disorders require multiple blood transfusions, which may lead to alloimmunization because of mismatched blood group antigens. In this study, we examined the alloimmunization and autoimmunization rates in patients with SCD and thalassemia together with the involved antibodies.Patients and Methods: A cross-sectional study was conducted to review the transfusion history records of patients with SCD and thalassemia at Prince Mohammed bin Nasser Hospital, Jazan Province, Saudi Arabia.Results: Four-hundred thirty-eight patients (385 with SCD, 52 with β-thalassemia, and 1 with α-thalassemia) were received leukoreduced red cell transfusions. The alloimmunization and autoimmunization rates in patients with SCD were 12.98% and 0.52%, respectively. In patients with thalassemia, the alloimmunization and autoimmunization rates were 13.21% and 3.77%, respectively. The most prevalent antibodies in the study population were anti-E (17.19%) and anti-K (14.06%).Conclusion: The alloimmunization and autoimmunization rates were determined in patients with SCD and thalassemia in Jazan Province, Saudi Arabia. The results highlight the need for extended phenotyping to include ABO, RH (D, C, c, E, e), K, Fya, Fyb, Jka and Jkb antigens in the screening panel. This will benefit patients to ensure better transfusion practices.Keywords: red cell alloimmunization, sickle cell disease, thalassemia, autoimmunization

Ashraf Albrakati,1 Khalaf F Alsharif,2 Naif E Al omairi,3 Walaa F Alsanie,2 Abdulraheem SA Almalki,4 Zakaria Y Abd Elmageed,5 Gehad E Elshopakey,6 Maha S Lokman,7,8 Amira A Bauomy,9 Ahmed E Abdel Moneim,8 Rami B Kassab8,10 1Department of Human Anatomy, College of Medicine, Taif University, Taif, Saudi Arabia; 2Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif, Saudi Arabia; 3Department of Internal Medicine, College of Medicine, Taif University, Taif, Saudi Arabia; 4Department of Chemistry, Faculty of Science, Taif University, Taif, Saudi Arabia; 5Department of Pharmacology, Edward via College of Osteopathic Medicine, University of Louisiana at Monroe, Monroe, LA, USA; 6Department of Clinical Pathology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt; 7Biology Department, College of Science and Humanities, Prince Sattam bin Abdul Aziz University, Alkharj, Saudi Arabia; 8Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo, Egypt; 9Department of Science Laboratories, College of Science and Arts, Qassim University, ArRassAl-Qassim, Saudi Arabia; 10Biology Department, Faculty of Science and Arts, Al Baha University, Al Makhwah Branch, Al Baha, Saudi ArabiaCorrespondence: Ahmed E Abdel MoneimDepartment of Zoology and Entomology, Faculty of Science, Helwan University, Cairo, EgyptTel +20 1153322079Email aest1977@hotmail.comPurpose: Depression is a mood disorder accompanied by intensive molecular and neurochemical alterations. Currently, available antidepressant therapies are not fully effective and are often accompanied by several adverse impacts. Accordingly, the ultimate goal of this investigation was to clarify the possible antidepressant effects of prodigiosins (PDGs) loaded with selenium nanoparticles (PDGs-SeNPs) in chronic unpredictable mild stress (CUMS)-induced depression-like behavior in rats.Methods: Sixty Sprague Dawley rats were randomly allocated into six groups: control, CUMS group (depression model), fluoxetine (Flu, 10 mg/kg)+CUMS, PDGs+CUMS (300 mg/kg), sodium selenite (Na2SeO3, 400 mg/kg)+CUMS, and PDGs-SeNPs+CUMS (200 mg/kg). All treatments were applied orally for 28 consecutive days.Results: PDGs-SeNPs administration prevented oxidative insults in hippocampal tissue, as demonstrated by decreased oxidant levels (nitric oxide and malondialdehyde) and elevated innate antioxidants (glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase), in addition to the upregulated expression of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 in rats exposed to CUMS. Additionally, PDGs-SeNPs administration suppressed neuroinflammation in hippocampal tissue, as determined by the decreased production of pro-inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1β, and interleukin-6), increased anti-inflammatory cytokine interleukin-10, and decreased inflammatory mediators (prostaglandin E2, cyclooxygenase-2, and nuclear factor kappa B). Moreover, PDGs-SeNPs administration in stressed rats inhibited neuronal loss and the development of hippocampal apoptosis through enhanced levels of B cell lymphoma 2 and decreased levels of caspase 3 and Bcl-2-associated X protein. Interestingly, PDGs-SeNPs administration improved hormonal levels typically disrupted by CUMS exposure and significantly modulated hippocampal levels of monoamines, brain-derived neurotrophic factor, monoamine oxidase, and acetylcholinesterase activities, in addition to upregulating the immunoreactivity of glial fibrillary acidic protein in CUMS model rats.Conclusion: PDGs-SeNPs may serve as a prospective antidepressant candidate due to their potent antioxidant, anti-inflammatory, and neuroprotective potential.Keywords: chronic unpredictable mild stress, prodigiosin-loaded selenium nanoparticles, oxidative stress, neuroinflammation, apoptosis, neurochemical markers

Background: The 2023 dengue outbreak has proven that dengue is not only an endemic disease but also an emerging health threat in Bangladesh. Integrated studies on the epidemiology, clinical characteristics, seasonality, and genotype of dengue are limited. This study was conducted to determine recent trends in the molecular epidemiology, clinical features, and seasonality of dengue outbreaks., Methods: We analyzed data from 41 original studies, extracting epidemiological information from all 41 articles, clinical symptoms from 30 articles, and genotypic diversity from 11 articles. The study adhered to the standards of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) Statement and Cochrane Collaboration guidelines., Results: A total of 565,438 dengue cases and 2,587 fatalities were documented from January 2000 to March 2024. Notably, 60% of cases during the 2019 and 2023 outbreaks were reported in regions previously considered non-endemic. Fatalities were more frequent among women (70%). The majority of the studies (95-100%) used the NS1Ag test, followed by IgG or IgM and RT-PCR tests. New hotspots of dengue transmission were identified in the southern (Khulna, 10.8% and Barishal, 11.8%) and southeastern (Chattogram, 13.8%) regions of Bangladesh. Serotyping was conducted on 92.4% (1,456 of 1,575) of isolates between 2012 and 2023. Of the four serotypes, DENV3 was the most prevalent (57%), followed by DENV2 (30%), DENV1 (11%), and DENV4 (<1%). Genotype DENV3-I (43 of 59 isolates) was the most prevalent, followed by DENV3-II (8 of 59). The highest frequency of dengue cases was observed in August (26.3%), followed by September (22.5%), October (20.2%), and November (13.08%). Fever (90.51, 95% CI 85-100%) was the most prevalent symptom, followed by headache (57.98, 95% CI 12-100%), vomiting (51.16, 95% CI 23-91%), abdominal pain (34.12, 95% CI 12-85%), and myalgia (25.53, 95% CI 13-85%), respectively., Conclusion: This study provides integrated insights into the molecular epidemiology, clinical features, seasonality, and transmission of dengue in Bangladesh and highlights research gaps for future studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sharif, Opu, Saha, Masud, Naim, Alsharif, Alzahrani, Alvarado, Noya, De la Torre Díez and Dey.)

Alkaloids, a diverse class of naturally occurring compounds, have shown significant potential in the treatment of leukemia by targeting key molecular pathways and cellular mechanisms. This review discusses several potent alkaloids, such as homoharringtonine, chaetominine, matrine, and jerantinine B, which induce apoptosis, cell cycle arrest, and autophagy and inhibit signaling pathways including PI3K/Akt/mTOR, MAPK, and NF-κB. For instance, homoharringtonine induces apoptosis in acute myeloid leukemia (AML) cells via the SP1/TET1/5hmC/FLT3/MYC axis, while chaetominine enhances chemosensitivity by inhibiting the PI3K/Akt/Nrf2 pathway. In addition, targeting leukemia stem cells (LSCs) with alkaloids such as zalypsis offers promise due to its ability to induce apoptosis without significantly affecting normal hematopoietic stem cells. The modulation of the immune response, such as the inhibition of NF-κB activation by noscapine, further underscores the potential of alkaloids in overcoming treatment resistance. Various studies have demonstrated the efficacy of alkaloids across different leukemia types. For example, jerantinine B targets AML cells, while vincristine has shown success in lymphocytic leukemia. Clinical trials have also highlighted the benefits of alkaloids, including homoharringtonine, which achieved a 79.9% complete remission rate in AML patients. However, adverse effects such as neutropenia and hepatotoxicity necessitate careful management. Collectively, these findings emphasize the need for further research into alkaloid-based combination therapies to enhance efficacy and minimize toxicity, providing a promising avenue for innovative leukemia treatments., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Lung cancer ranks as one of the most rapidly growing malignancies. Which is characterized by its poor prognosis and a low survival rate due to late diagnosis and limited efficacy of conventional treatments. In recent years nanotechnology has emerged as a promising frontier in the management of lung cancer, presenting novel strategies to enhance drug administration, improve therapeutic efficiency, and mitigate side effects. This research comprehensively evaluates the current state and research trends concerning the application of nanomaterials in lung cancer through bibliometric analysis., Materials and Methods: We employed a systematic approach by retrieving studies from the Scopus database that focused on nanomaterials and lung cancer between 2003 and 2023. Subsequently, we carefully selected relevant articles based on predetermined inclusion criteria. The selected publications were then subjected to bibliometric and visual analysis using softwares such as VOSviewer and Biblioshiny., Results: A total of 3523 studies that meet inclusion criteria were selected for bibliometric analysis. We observed a progressive increase in the number of annual publications from 2003 to 2023, indicating the growing interest in this field. According to our analysis, China is the primary contributor to publication output among the countries. The "Ministry of Education of the People's Republic of China" was the most influential institution. Among the authors, "Dr. Jack A. Roth" and "Dr. Huang Leaf" had the highest number of publications and cited publications, respectively. The "International Journal of Nanomedicine" was found to be the most prolific journal in this field. Additionally, "Biomaterials" emerged as the most cited journal. Through keyword analysis, we identified five main research themes and future research directions; nono-immunotherapy and green synthesis are the hot topics in this research field., Conclusion: Our study summarized the key characteristics of publications in this field and identified the most influential countries, institutions, authors, journals, hot topics, and trends related to the application of nanomaterials in lung cancer. These findings contribute to the existing body of knowledge and serve as a foundation for future research endeavors in this area. More effective efforts are needed in this field to reduce the burden of lung cancer and help achieve the United Nation's Sustainable Development Goals., (© 2024. The Author(s).)

Research suggests curcumin's safety and efficacy, prompting interest in its use for treating and preventing various human diseases. The current study aimed to predict drag ability of methyl substituted curcumin derivatives (BL1 to BL4) using SwissADME and Density Functional Theory (DFT) approaches. The curcumin derivatives investigated mostly adhere to Lipinski's rule of five, with molecular properties including MW, F. Csp3, nHBA, nHBD, and TPSA falling within acceptable limits. The compounds demonstrating high lipophilicity while poor water solubility. The pharmacokinetic evaluation revealed favorable gastrointestinal absorption and blood-brain barrier permeation while none were identified as substrates for P-glycoprotein, however, revealed inhibitory actions against various cytochrome P450 enzymes. Additionally, all derivatives exhibited a consistent bioavailability score of 0.55. Similarly, the DFT computations of the compounds of the curcumin derivatives were conducted at B3LYP/6-311 G** level to predict and then assess the key electronic characteristics underlying the bioactivity. Accordingly, the BL4 molecule (ΔE gap = 4.105 eV) would prefer to interact with the external molecular system more than the other molecules due to having the biggest energy gap. The ΔN max (2.328 eV) and Δε back-donat. (-0.446 eV) scores implied that BL1 would have more charge transfer capability and the lowest stability via back donation among the compounds. In short, the derivative (BL1 to BL4) exhibited strong extrinsic therapeutic properties and therefore stand eligible for further in vitro and in vivo studies., 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. Conflict of interest The authors of this article declare no conflict of interest, (Copyright © 2024. Published by Elsevier Ltd.)

Stem cell therapy has emerged as a promising approach for regenerative medicine, offering potential treatments for a wide range of diseases and injuries. Although stem cell therapy has great promise, several obstacles have prevented its broad clinical adoption. The effectiveness of therapy has been inhibited by problems such as ineffective stem cell differentiation, low post-transplantation survival rates, and restricted control over stem cell behaviour. Furthermore, the implementation of stem cell therapies is further complicated by the possibility of immunological rejection and cancer. Innovative strategies that provide precise control over stem cell characteristics and maximize their therapeutic potential are desperately needed to overcome these obstacles. Recent studies have shown that the effectiveness of stem cell treatments can be greatly increased by nanoscale advances. By establishing an ideal microenvironment and precisely offering growth factors, nanomaterials such as nanoparticles, nanocomposites, and quantum dots have been demonstrated to improve stem cell differentiation and proliferation. This article provides an overview of the recent trends and applications of nanoscale innovations in the context of stem cell therapy. The recent development of precision medicine has been facilitated by the incorporation of nanotechnology into stem cell therapy. The ability to manipulate stem cells at the nanoscale offers unprecedented control over their behavior and function, opening up exciting possibilities for personalized and highly effective therapeutic interventions. This review paper highlights the recent trends and applications of nanotechnology in advancing stem cell therapy, showcasing its potential to revolutionize regenerative medicine., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Asiatic acid (AA) is a polyphenolic compound with potent antioxidative and anti-inflammatory activities that make it a potential choice to attenuate inflammation and oxidative insults associated with ulcerative colitis (UC). Hence, the present study aimed to evaluate if AA can attenuate molecular, biochemical, and histological alterations in the acetic acid-induced UC model in rats. To perform the study, five groups were applied, including the control, acetic acid-induced UC, UC-treated with 40 mg/kg aminosalicylate (5-ASA), UC-treated with 20 mg/kg AA, and UC-treated with 40 mg/kg AA. Levels of different markers of inflammation, oxidative stress, and apoptosis were studied along with histological approaches. The induction of UC increased the levels of lipid peroxidation (LPO) and nitric oxide (NO). Additionally, the nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant proteins [catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GPx), and glutathione reductase (GR)] were down-regulated in the colon tissue. Moreover, the inflammatory mediators [myeloperoxidase (MPO), monocyte chemotactic protein 1 (MCP1), prostaglandin E2 (PGE2), nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β)] were increased in the colon tissue after the induction of UC. Notably, an apoptotic response was developed, as demonstrated by the increased caspase-3 and Bax and decreased Bcl2. Interestingly, AA administration at both doses lessened the molecular, biochemical, and histopathological changes following the induction in the colon tissue of UC. In conclusion, AA could improve the antioxidative status and attenuate the inflammatory and apoptotic challenges associated with UC., (© 2024 The Author(s).)

Background: The global pandemic, known as the coronavirus disease 2019 (COVID-19) and caused by the severe acute respiratory syndrome, coronavirus 2 (SARS-CoV-2), poses a significant threat, particularly to individuals with comorbidities such as hypertension, chronic obstructive pulmonary disease (COPD), diabetes, HIV, cardiovascular disease (CVD), and cancer., Methods: This descriptive retrospective study investigates the impact of comorbidities on COVID-19-positive patients. The study includes individuals that were tested positive for SARS-CoV-2 via polymerase chain reaction at the Security Forces Hospital, Makkah, KSA, between February, 2022, and June, 2022. A total of 208 patients (107 males, 101 females) were examined, and the laboratory results revealed normal parameters., Results: An analysis indicates that 86.5% of the patients were discharged, 2.9% remained hospitalized, and 10.6% succumbed to the disease, indicating a 10.6% mortality rate among comorbid COVID-19-positive patients. Notably, the study identifies specific comorbidities (chronic kidney disease, diabetes mellitus, hypertension) and changes in laboratory parameters (red blood cells, hemoglobin, C-reactive protein, white blood cells, ferritin, D-dimer, ALT, troponin, LDH, neutrophils) associated with ICU admission during hospitalization., Conclusions: This study underscores the critical impact of comorbidities, such as chronic kidney disease, diabetes, and hypertension, on the clinical outcomes of COVID-19-positive patients. The identification of specific laboratory parameters linked with ICU admission provides valuable insights for risk stratification and tailored management strategies.

Introduction: The expression pattern of CD27 and CD44 was found to correlate with the differentiation stages of B cell precursors, which were known to be involved in a variety of immunological responses., Aim of the Study: This study aimed to determine the biological significance of CD27 and CD44 expression in patients with B-precursor acute lymphoblastic leukemia (B-ALL), as well as their association with standard prognostic factors and therapeutic response., Patients and Methods: This case-control study included 60 pediatric patients newly diagnosed with B-ALL and 30 pediatric controls. The patient CD27 and CD44 levels were measured using the Beckman Coulter Navios Flow Cytometer., Results: Most malignant cells (91.6 %) expressed CD44, but only 50 % of the patients had CD27 expressed. The positive CD 44 expression was associated with unfavorable prognostic markers, including a decrease., Competing Interests: Conflicts of interest The author(s) declare no potential conflicts of interest, with respect to the research, authorship and/or publication of this article., (Copyright © 2023 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. All rights reserved.)

Acute kidney injury (AKI) is a life-threatening complication that accompanies rhabdomyolysis. Daidzein is a dietary isoflavone that has various biological activities. This study examined the therapeutic potential of daidzein and the underlying mechanisms against AKI induced by glycerol in male rats. Animals were injected once with glycerol (50%, 10 ml/kg, intramuscular) for induction of AKI and pre-treated orally with daidzein (25, 50, and 100 mg/kg) for 2 weeks. Biochemical, histopathological, immunohistopathological, and molecular parameters were assessed to evaluate the effect of daidzein. The results revealed that the model group displayed remarkable functional, molecular, and structural changes in the kidney. However, pre-administration of daidzein markedly decreased the kidney relative weight as well as the levels of urea, creatinine, K, P, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and cystatin C. Further, daidzein lessened the rhabdomyolysis-related markers [lactate dehydrogenase (LDH) and creatine kinase (CK)]. Notably, the enhancement of the antioxidant biomarkers [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and reduced glutathione (GSH) is accompanied by a decrease in malondialdehyde (MDA) and nitric oxide (NO) levels. Moreover, upregulated gene expression levels of nuclear factor erythroid 2-related factor 2 (Nfe212) and hemeoxygenase-1 (Hmox1) were exerted by daidzein administration. Rats who received daidzein displayed markedly lower interleukin-1β (IL-1β), tumor nuclear factor-α (TNF-α), myleoperoxidase (MPO), and nuclear factor kappa B (NF-κB) levels together with higher interleukin-10 (IL-10) related to the model group. Remarkably, significant declines were noticed in the pro-apoptotic (Bax and caspase-3) and rises in antiapoptotic (Bcl-2) levels in the group that received daidzein. The renal histological screening validated the aforementioned biochemical and molecular alterations. Our findings support daidzein as a potential therapeutic approach against AKI-induced renal injury via suppression of muscle degradation, oxidative damage, cytokine release, and apoptosis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Diabetes mellitus is a complex metabolic syndrome that involves dysfunction of spleen and other lymphoid organs. Medicinal plants, including okra ( Abelmoschus esculentus (L.) Moench), were used widely for diabetes treatment. Scarce data are available about the potential anti-diabetic effects of okra, the histopathological alterations in splenic tissues and the mechanistic pathways underlying this association. The current research investigated the effects of okra pod extract on the biochemical parameters and expression of CD8 + T cells and nuclear factor kappa (NF-k) B and releasing proinflammatory cytokines in spleen in streptozotocin (STZ)-induced diabetic rat models. A total of 50 mature male Wister albino rats were divided into five isolated groups; the first served as control (untreated) animals, the second (DM group) diabetes induced by STZ (at a dose of 45 mg/kg body weight, administered intraperitoneally), the third group (DM + Insulin): diabetic rats administered insulin subcutaneously (10 units/kg bw/day) daily for 4 weeks, the fourth group was administrated 400 mg/kg okra extract daily for 4 weeks, and diabetic induced rats in the fifth group were administrated 400 mg/kg okra extract daily for 4 weeks. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity in Abelmoschus esculentus (L.) Moench was studied, and the content of phenolic compounds in okra pods was estimated using high-performance liquid chromatography. Diabetes induction led to decreased body weight, increased blood glucose levels. Capsular thickness was significantly increased, white pulp was widely dispersed, and mature lymphocytes in the periphery were also drastically decreased, with thick follicular arteries, necrosis, and depletion of lymphocytes in the germinal center. Red pulp revealed severe congestion and degenerative changes, deposition of hemosiderin granules and lymphocytic depletion. In addition, collagen fiber deposition was increased also in this group. The induction of diabetes exaggerated NF-kβ expression and mediated downregulation of the expression of CD8 + T cells in spleen tissue. Interestingly, oral administration of okra extracts post diabetes induction could mitigate and reverse such adverse effects. Altogether, our study points out the potential benefits of okra in improving blood glucose levels and restoring histopathological alterations in splenic tissues through CD8 + T cells and NF-kβ expression in a diabetic rat model., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Alblihd, Alsharif, Hamad, Ali, Hussein, Alhegaili, Hassan, Al-Amer, Albezrah, Almalki, Albarakati, Alghamdi, Alzahrani, Albrakati, Alrubai, ElAshmouny and Elmahallawy.)

Background: Alpha-thalassemia (α-thalassemia) is one of the most common monogenic diseases in Saudi Arabia and is associated with significant morbidity. Premarital testing programs in Saudi Arabia reduce the burden of hemoglobinopathy disorders, and ongoing monitoring is required. We aimed to explore the molecular nature of α-globin genes and identify the most common genotypes and regions with a high risk of α-thalassemia in Saudi Arabia., Methods: This retrospective study was conducted between January 2021 and December 2022. Six hundred twenty-five samples from patients with microcytic hypochromic anemia in Saudi Arabia were analyzed using reverse dot blot hybridization (RDBH)-based multiplex-PCR, which screens for the known 21 mutations of α-globin genes., Results: Seven mutations in the α-globin gene were identified in 88.96% (556) patients. The most frequent abnormality of a-globin genes was -α 3.7 (62.3%), followed by α2 IVS1(-5nt) (20.7%) and α2 polyA-1 (α2 T.Saudi ) (14.1%). Interestingly, α2 polyA-2 (α2 T.Turkish ) was identified in Saudi and presented with -MED, causing Haemoglobin H disease. The incidence of α-thalassemia in Saudi Arabia's cities showed significant differences (P = 0.004). Jeddah City had the highest percentage of cases (25%), followed by Makkah (23%), Taif (13.3%), and Al-Ahassa (12.4%)., Conclusion: The study provides current knowledge about the molecular nature of α- thalassemia, highlights the common genotypes that could contribute to disease occurrence in the Saudi population, and sheds light on Saudi regions with a high incidence. It also recommends further studies in a larger population and with differently composed molecular assays to verify these findings., (© 2023. The Author(s).)

Background: Tobacco use by youth is ever-demanding, and it is increasingly distributed not only in India but also globally. Saliva is a complex oral bio-fluid, freely available, performing absolute tasks for maintaining oral health and homeostasis. It contains a plethora of significant constituents such as proline-rich proteins (PRPs), immunoglobulins, IgA, enzymes lysozyme, lactoferrin, peroxidases, amylase, etc. The basic ecological balance of the oral cavity is stabilized via salivary clearance by reduced aggregation and adherence of microorganisms by direct microbial activity. This balance of oral activity is also done by indirect mechanisms by immunological as well as non-immunological means and also by effectively regulating salivary pH flow rate. This institutional observational study was planned to assess and compare salivary parameters (pH, salivary flow rate), total proteins, α-amylase, calcium, phosphate, and IgA, of unstimulated whole saliva of both tobacco abusers and tobacco non-users., Methods: The Study consisted of 270 participants (Tobacco habit) group, n = 135 and Control (Healthy) group, n = 135 and were in the age range of 20-50 years. They were assessed for oral health status, followed by the analysis of salivary pH, flow rate, total proteins, amylase, calcium, phosphates, and IgA of unstimulated whole saliva., Results: Comparative evaluation of salivary parameters among groups found that varying tobacco abusers had increased salivary amylase, protein levels, and phosphate whereas decreased salivary pH, flow rate, IgA, and in the whole unstimulated saliva samples than those of non-tobacco users. This difference among groups was statistically significant. ( p < 0.05), and calcium levels were not altered significantly., Conclusions: This study concludes that salivary parameters are altered in tobacco abusers when compared to those of non-abusers, and it was more significant in smokeless tobacco abusers than in any other form of tobacco abuse., Competing Interests: Given Rodolfo Reda’s role as Guest Editor and Luca Testarelli’s role as Guest Editor and Editorial Board member of the journal, they had no involvement in the peer-review of this article and has no access to information regarding its peer-review. Full responsibility for the editorial process for this article was delegated to Ru Chen. The authors declare no conflict of interest., (© 2023 The Author(s). Published by IMR Press.)

Background: Diabetes mellitus (DM) is a chronic metabolic disorder. Hepatopathy is one of the serious effects of DM Melatonin (MT) is a potent endogenous antioxidant that can control insulin output. However, little information is available about the potential association between melatonin and hepatic alpha-fetoprotein expression in diabetes., Objective: This study was conducted to assess the influence of MT on diabetes-related hepatic injuries and to determine how β-cells of the pancreas in diabetic rats respond to MT administration., Materials and Methods: Forty rats were assigned to four groups at random (ten animals per group). Group I served as a normal control group. Group II was induced with DM, and a single dose of freshly prepared streptozotocin (45 mg/kg body weight) was intraperitoneally injected. In Group III, rats received 10 mg/kg/day of intraperitoneal melatonin (IP MT) intraperitoneally over a period of 4 weeks. In Group IV (DM + MT), following the induction of diabetes, rats received MT (the same as in Group III). Fasting blood sugar, glycosylated hemoglobin (HbA1c), and serum insulin levels were assessed at the end of the experimental period. Serum liver function tests were performed. The pancreas and liver were examined histopathologically and immunohistochemically for insulin and alpha-fetoprotein (AFP) antibodies, respectively., Results: MT was found to significantly modulate the raised blood glucose, HbA1c, and insulin levels induced by diabetes, as well as the decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Furthermore, MT attenuated diabetic degenerative changes in the pancreas and the hepatic histological structure, increased the β-cell percentage area, and decreased AFP expression in the liver tissue. It attenuated diabetes-induced hepatic injury by restoring pancreatic β-cells; its antioxidant effect also reduced hepatocyte injury., Conclusion: Collectively, the present study confirmed the potential benefits of MT in downregulating the increased hepatic alpha-fetoprotein expression and in restoring pancreatic β-cells in a streptozotocin-induced diabetic rat model, suggesting its promising role in the treatment of diabetes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Alsharif, Hamad, Alblihd, Ali, Mohammed, Theyab, Al-Amer, Almuqati, Almalki, Albarakati, Alzahrani, Albrakati, Albarakati, Abass, Lokman and Elmahallawy.)

Background: Human nucleotide triphosphate diphosphatase (NUDT15) is one of the essential proteins involved in the hydrolysis of anti-cancer drugs against leukemia. Polymorphisms in NUDT15 significantly affect the hydrolysis activity that leads to side effects, including leucopenia. Drugs having a better affinity with NUDT15 protein and contributing stable conformation may benefit patients from leucopenia. Most frequent NUDT15 polymorphisms causing structure variability and their association with leukemia were screened. The selected protein variants and anti-cancer drug structures were collected. Further, molecular docking was performed between drugs and NUDT15 variants along with the wild-type. Finally, molecular dynamics were executed for 100 ns to understand the stability of the protein with the anti-cancer drug based on molecular trajectories., Results: Three-dimensional structures of NUDT15 wild, the most frequent variants (Val18Ile, Arg139Cys, and Arg139), and the anti-cancer drugs (azathioprine, mercaptopurine, and thioguanine) were selected and retrieved from structure databases. On molecular docking the binding energies of anti-cancer drugs against NUDT15 structures ranged from - 5.0 to - 5.9 kcal/mol. Among them, azathioprine showed the highest affinities (- 7.3 kcal/mol) for the wild and variant structures. Additionally, the molecular dynamics suggest all analyzed NUDT15 were stable with azathioprine based on the dynamic trajectories., Conclusion: Our results suggest azathioprine could be the preferable anti-cancer drug for the population with NUDT15 variants that could effectively be hydrolyzed as evidenced by molecular docking and dynamic simulation., (© 2023. Academy of Scientific Research and Technology.)

Phytol (Pyt), a diterpenoid, possesses many important bioactivities. This study evaluates the anticancer effects of Pyt on sarcoma 180 (S-180) and human leukemia (HL-60) cell lines. For this purpose, cells were treated with Pyt (4.72, 7.08, or 14.16 μM) and a cell viability assay was performed. Additionally, the alkaline comet assay and micronucleus test with cytokinesis were also performed using doxorubicin (6 μM) and hydrogen peroxide (10 mM) as positive controls and stressors, respectively. Results revealed that Pyt significantly reduced the viability and rate of division in S-180 and HL-60 cells with IC 50 values of 18.98 ± 3.79 and 1.17 ± 0.34 μM, respectively. Pyt at 14.16 μM exerted aneugenic and/or clastogenic effects in S-180 and HL-60 cells, where the number of micronuclei and other nuclear abnormalities (e.g., nucleoplasmic bridges and nuclear buds) were frequently observed. Moreover, Pyt at all concentrations induced apoptosis and showed necrosis at 14.16 μM, suggesting its anticancer effects on the tested cancer cell lines. Taken together, Pyt showed promising anticancer effects, possibly through inducing apoptosis and necrosis mechanisms, and it exerted aneugenic and/or clastogenic effects on the S-180 and HL-60 cell lines., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Malignant melanoma is the most dangerous type of skin cancer. It is becoming more common globally and is increasingly resistant to treatment options. Despite extensive research into its pathophysiology, there are still no proven cures for metastatic melanoma. Unfortunately, current treatments are frequently ineffective and costly, and have several adverse effects. Natural substances have been extensively researched for their anti-MM capabilities. Chemoprevention and adjuvant therapy with natural products is an emerging strategy to prevent, cure or treat melanoma. Numerous prospective drugs are found in aquatic species, providing a plentiful supply of lead cytotoxic chemicals for cancer treatment. Anticancer peptides are less harmful to healthy cells and cure cancer through several different methods, such as altered cell viability, apoptosis, angiogenesis/metastasis suppression, microtubule balance disturbances and targeting lipid composition of the cancer cell membrane. This review addresses marine peptides as effective and safe treatments for MM and details their molecular mechanisms of action., 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. Published by Elsevier Inc.)

Silver nanoparticles (AgNPs) are the most common nanomaterials in consumer products. Therefore, it has been crucial to control AgNPs toxicological effects to improve their safety and increase the outcome of their applications. This work investigated the possible protective effect of thymoquinone (TQ) against AgNPs-induced hepatic and renal cytotoxicity in rats. Serum markers of liver and kidney functions as well as liver and kidney oxidative stress status, pro-inflammatory cytokines, apoptosis markers, and histopathology were assessed. TQ reversed AgNPs-induced elevation in serum liver and kidney function markers, including aspartate transaminase, alanine transaminase, urea, and creatinine. Moreover, TQ co-administration with AgNPs alleviates hepatic and renal oxidative insults by decreasing MDA and NO levels with a significant increase in the activity of antioxidant enzymes (superoxide dismutase, catalase, and glutathione recycling enzymes peroxidase and reductase) compared to AgNPs-treated rats. Besides, TQ upregulated hepatic and renal Nrf2 gene expression in AgNPs-intoxicated rats. Furthermore, TQ co-administration decreased the hepatic and renal pro-inflammatory mediators represented by IL-1β, TNF-α, TGF-β, and NF-κB levels. Besides, TQ co-administration decreased apoptotic protein (Bax) levels and increased the anti-apoptotic protein (Bcl-2) levels. These findings were confirmed by the histopathological examination of hepatic and renal tissues. Our data affirmed the protective effect of TQ against AgNPs cytotoxicity and proposed a possible mechanism of TQ antioxidant, anti-inflammatory, and anti-apoptotic effects. Consequently, we could conclude that using TQ might control AgNPs toxicological effects, improve their safety, and increase the outcome of their applications., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Computational pharmacology and chemistry of drug-like properties along with pharmacokinetic studies have made it more amenable to decide or predict a potential drug candidate. 4-Hydroxyisoleucine is a pharmacologically active natural product with prominent antidiabetic properties. In this study, ADMETLab 2.0 was used to determine its important drug-related properties. 4-Hydroxyisoleucine is compliant with important drug-like physicochemical properties and pharma giants' drug-ability rules like Lipinski's, Pfizer, and GlaxoSmithKline (GSK) rules. Pharmacokinetically, it has been predicted to have satisfactory cell permeability. Blood-brain barrier permeation may add central nervous system (CNS) effects, while a very slight probability of being CYP2C9 substrate exists. None of the well-known toxicities were predicted in silico , being congruent with wet lab results, except for a "very slight risk" for respiratory toxicity predicted. The molecule is non ecotoxic as analyzed with common indicators such as bioconcentration and LC 50 for fathead minnow and daphnia magna . The toxicity parameters identified 4-hydroxyisoleucine as non-toxic to androgen receptors, PPAR-γ, mitochondrial membrane receptor, heat shock element, and p53. However, out of seven parameters, not even a single toxicophore was found. The density functional theory (DFT) study provided support to the findings obtained from drug-like property predictions. Hence, it is a very logical approach to proceed further with a detailed pharmacokinetics and drug development process for 4-hydroxyisoleucine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ahmad, Kuznetsov, Pirzada, Alsharif, Daglia and Khan.)

Melatonin possesses a wide range of pharmacological activities, including antidiabetic properties. Diabetes mellitus (DM) induces several physiopathological changes in body organs, which could be observed lately after systemic failure. In the current study, we aimed to investigate the serobiochemical changes and the histopathological picture in the diabetic heart and the kidney early before chronic complications and highlight the association between hyperglycemia, glomerular alterations, and cardiovascular changes. In addition, the role of melatonin in the treatment of cardio-nephro diabetic vascular and cellular adverse changes in streptozotocin-induced diabetic rats was also studied. A total of 40 mature Wistar albino rats were distributed into five groups; (1) control untreated rats, (2) diabetic mellitus untreated (DM) rats, in which DM was induced by the injection of streptozotocin (STZ), (3) control melatonin-treated (MLT), (4) melatonin-treated diabetic (DM + MLT) rats, in which melatonin was injected (10 mg/kg/day, i.p.) for 4 weeks, and (5) insulin-treated diabetic (DM + INS) rats. The serum biochemical analysis of diabetic STZ rats showed a significant ( P < 0.05) increase in the concentrations of blood glucose, total oxidative capacity (TOC), CK-MB, endothelin-1, myoglobin, H-FABP, ALT, AST, urea, and creatinine as compared to control rats. In contrast, there was a significant ( P < 0.05) decrease in serum concentration of insulin, total antioxidative capacity (TAC), total nitric oxide (TNO), and total protein level in DM rats vs. the control rats. Significant improvement in the serobiochemical parameters was noticed in both (DM + MLT) and (DM + INS) groups as compared with (DM) rats. The histological examination of the DM group revealed a disorder of myofibers, cardiomyocyte nuclei, and an increase in connective tissue deposits in between cardiac tissues. Severe congestion and dilation of blood capillaries between cardiac muscle fibers were also observed. The nephropathic changes in DM rats revealed various deteriorations in glomeruli and renal tubular cells of the same group. In addition, vascular alterations in the arcuate artery at the corticomedullary junction and interstitial congestion take place. Melatonin administration repaired all these histopathological alterations to near-control levels. The study concluded that melatonin could be an effective therapeutic molecule for restoring serobiochemical and tissue histopathological alterations during diabetes mellitus., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Elmahallawy, Alsharif, Alblihd, Hamad, Nasreldin, Alsanie, Aljoudi, Oyouni, Al-Amer, Albarakati, Lokman, Albrakati and Ali.)

Exposure to lead (Pb) is associated with serious health problems including hepatorenal toxicity. Apigenin is a natural-sourced flavonoid with promising antioxidant and anti-inflammatory effects. In this research, we investigated the potential protective role of apigenin against lead acetate (PbAc)-induced hepatorenal damage. Thus, this experiment studied the exposure of male Wistar Albino rats to apigenin and/or PbAc and their effects in comparison to the control rats. Apigenin administration decreased the levels of Pb and prevented the histopathological deformations in liver and kidney tissues following PbAc exposure. This was confirmed by the normalized levels of liver and kidney function markers. Additionally, apigenin inhibited significantly oxidative reactions through upregulating Nrf2 and HO-1, and activating their downstreamed antioxidants accompanied by a marked depletion of pro-oxidants. Moreover, apigenin decreased the elevated pro-inflammatory cytokines and inhibited cell loss in liver and kidney tissues in response to PbAc intoxication in both tissues. The obtained results demonstrated that apigenin could be used to attenuate the molecular, biochemical, and histological alterations associated with Pb exposure due to its potent antioxidant, anti-inflammatory, and antiapoptotic effects., (© 2022 Wiley Periodicals LLC.)

The COVID-19 pandemic has triggered intensive research and development of drugs and vaccines against SARS-CoV-2 during the last two years. The major success was especially observed with development of vaccines based on viral vectors, nucleic acids and whole viral particles, which have received emergent authorization leading to global mass vaccinations. Although the vaccine programs have made a big impact on COVID-19 spread and severity, emerging novel variants have raised serious concerns about vaccine efficacy. Due to the urgent demand, drug development had originally to rely on repurposing of antiviral drugs developed against other infectious diseases. For both drug and vaccine development the focus has been mainly on SARS-CoV-2 surface proteins and host cell receptors involved in viral attachment and entry. In this review, we expand the spectrum of SARS-CoV-2 targets by investigating the COVID-19 signalome. In addition to the SARS-CoV-2 Spike protein, the envelope, membrane, and nucleoprotein targets have been subjected to research. Moreover, viral proteases have presented the possibility to develop different strategies for the inhibition of SARS-CoV-2 replication and spread. Several signaling pathways involving the renin-angiotensin system, angiotensin-converting enzymes, immune pathways, hypoxia, and calcium signaling have provided attractive alternative targets for more efficient drug development., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The findings of earlier investigations of antiapoptotic gene genotypes and allele variants on lymphoma risk are ambiguous. This study aimed to examine the relationship between the mutation in the antiapoptotic genes and lymphoma risk among Saudi patients., Methods: This case-control study included 205 patients, 100 of whom had lymphoma (cases) and 105 who were healthy volunteers (controls). We used tetra amplification refractory mutation polymerase chain reaction (PCR) to identify antiapoptotic genes such as B-cell lymphoma-2 (BCL2-938 C > A), MCL1-rs9803935 T > G, and survivin (BIRC5-rs17882312 G > C and BIRC5-rs9904341 G > C). Allelic-specific PCR was used to identify alleles such as BIRC5-C , MCL1-G , and BIRC5-G ., Results: The dominant inheritance model among cases showed that mutations in all four antiapoptotic genes were more likely to be associated with the risk of lymphoma by the odds of 2.0-, 1.98-, 3.90-, and 3.29-fold, respectively, compared to controls. Apart from the BCL-2-A allele, all three specified alleles were more likely to be associated with lymphoma by the odds of 2.04-, 1.65-, and 2.11-fold, respectively., Conclusion: Unlike healthy individuals, lymphoma patients are more likely to have antiapoptotic gene genotypes and allele variants, apart from BCL-2-A alterations. In the future, these findings could be used to classify and identify patients at risk of lymphoma.

Prodigiosin (PDG) is a bacterial metabolite with numerous biological and pharmaceutical properties. Exposure to aluminium is considered a root etiological factor in the pathological progress of Alzheimer's disease (AD). Here, in this investigation, we explored the neuroprotective potential of PDG against aluminium chloride (AlCl 3 )-mediated AD-like neurological alterations in rats. For this purpose, rats were gavaged either AlCl 3 (100 mg/kg), PDG (300 mg/kg), or both for 42 days. As a result of the analyzes performed on the hippocampal tissue, it was observed that AlCl 3 induced biochemical, molecular, and histopathological changes like those related to AD. PDG pre-treatment significantly decreased acetylcholinesterase activity and restored the levels of brain-derived neurotrophic factor, monoamines (dopamine, norepinephrine, and serotonin), and transmembrane protein (Na + /K + -ATPase). Furthermore, PDG boosted the hippocampal antioxidant capacity, as shown by the increased superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione contents. These findings were accompanied by decreases in malondialdehyde and nitric oxide levels. The antioxidant effect may promote the upregulation of the expression of antioxidant genes (Nrf2 and HO-1). Moreover, PDG exerted notable anti-inflammatory effects via the lessening of interleukin-1 beta, tumor necrosis factor-alpha, cyclooxygenase-2, nuclear factor kappa B, and decreases in the gene expression of inducible nitric oxide synthase. In addition, noteworthy decreases in pro-apoptotic (Bax and caspase-3) levels and increases in anti-apoptotic (Bcl-2) biomarkers suggested an anti-apoptotic effect of PDG. In support, the hippocampal histological examination validated the aforementioned changes. To summarize, the promising neuromodulatory, antioxidative, anti-inflammatory, and anti-apoptotic activities of PDG establish it as a potent therapeutic option for AD., (© 2022 Wiley Periodicals LLC.)

5-Fluorouracil (5-FU) is a chemotherapy used to treat many types of cancer. Cardiotoxicity is one of the common drawbacks of 5-FU therapy. Quercetin (Qu) is a bioflavonoid with striking biological activities. This research aimed to assess the ameliorative effect of Qu against 5-FU-mediated cardiotoxicity. Thirty-five rats were allocated into five groups: control group (normal saline), 5-FU group (30 mg/kg, intraperitoneally), Qu group (50 mg/kg, oral), 25 mg/kg Qu+5-FU group, and 50 mg/kg Qu+5-FU. The experimental animals were received the above-mentioned drugs for 21 days. Results showed that 5-FU significantly elevated creatine kinase, lactate dehydrogenase, serum cholesterol and triglyceride, and upregulated troponin and renin mRNA expression. Additionally, cardiac oxidant/antioxidant imbalance was evident in elevated oxidants (malondialdehyde and nitric oxide) and depleted antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione). 5-FU also downregulated the gene expression of nuclear factor erythroid 2-related factor 2. Furthermore, 5-FU significantly increased cardiac pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-1 beta) and upregulated gene expression of nuclear factor kappa-B. 5-FU significantly enhanced cardiac apoptosis through upregulating caspase-3 expression and downregulating B-cell lymphoma 2. Immunohistochemical and histopathological examinations verified the above-mentioned findings. However, all these changes were significantly ameliorated in Qu pre-administered rats. Conclusively, Qu counteracted 5-FU-mediated cardiotoxicity through potent antioxidant, anti-inflammatory, and anti-apoptotic effects., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Thymoquinone (TQ) is an active constituent in Nigella sativa (black cumin) and is extensively reported for its distinguished antioxidant and anti-inflammatory bioactivities. Despite the local protective response of acute inflammation, it contributes to the development of various disease conditions such as cell death, organ damage, or carcinogenesis. Hence, in this study, the effects of orally administered TQ (50 mg/kg and 100 mg/kg) for 14 days against edema development, oxidative stress, and inflammation were investigated in paw edema induced by carrageenan in mice. Indomethacin (10 mg/kg) was used as a reference drug. The results revealed that TQ reduced the paw edema volume in a time-dependent manner, attenuated acetic acid-provoked writhing movements, and reduced xylene-triggered ear edema. Hematological findings revealed marked normalization of altered counts of WBCs, and platelets. Furthermore, paw tissue levels of malondialdehyde and nitric oxide showed marked decreases together with increases in nuclear factor erythroid 2-related factor 2, glutathione, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase after TQ administration. Additionally, TQ decreased pro-inflammatory mediators, such as interleukin-1 beta, tumor necrosis factor-alpha, interleukin-6, monocyte chemoattractant protein-1, C-reactive protein, myeloperoxidase, and nuclear factor kappa-B in the inflamed paw tissue. Moreover, appreciable decreases were recorded in cyclooxygenase-2 and its product prostaglandin E2 and the immune reaction of tumor necrosis factor-alpha in TQ-treated mice. Histopathological findings further validated the potential antiedematous, anti-inflammatory power of TQ in inflamed tissues. Conclusively, the results encourage the potent application of TQ to subside acute inflammatory events because of its striking antioxidant and anti-inflammatory properties in inflamed paw tissue., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Kidneys are among the vital organs of the human body; therefore, damage from any exogenous/endogenous agent may put human life at risk. Arachis hypogaea (AH) contains different free radical scavenging flavonoids, stilbenes, and tannins. This research aimed to elucidate the possible nephroprotective mechanism of AH methanolic crude extract (AHcr) and n-hexane oil fraction (AHO) against gentamycin-induced nephrotoxicity., Methods: After the extraction of the crude oil of the plant, they were tested against a Gentamycin (GM)-treated group of Swiss Albino mice for their nephroprotective action. Animals were divided into six (6) equal groups with five (5) animals in each group. These groups were: control group (0.5 mL normal saline via intraperitoneal -i.p), gentamycin group (gentamycin 100 mg/kg i.p), Silymarin + gentamycin group (Silymarin 50 mg/kg and gentamycin 100 mg/kg i.p), plant extract (AHcr1) and gentamycin group (AHcr1 250 mg/kg and gentamycin 100 mg/kg i.p), AHcr2 + gentamycin group (AHcr2; 500 mg/kg and gentamycin 100 mg/kg i.p) and the hexane oil fraction (AHO) + gentamycin (AHO 1 mL/kg and GM 100 mg/kg i.p). After completion of doses, animals were sacrificed for the collection of blood to further investigate biochemical changes and histopathological changes in kidney tissues., Results: Serum creatinine, urea, and blood urea nitrogen significantly increased ( p < 0.001) in the gentamycin-treated group as compared to the control group. The elevated level of serum creatinine, urea, and blood urea nitrogen was decreased significantly ( p < 0.001) in groups treated with AHcr and AHO compared to the gentamycin group. Similarly, the histopathological study of kidney tissues from the gentamycin group showed tubular necrosis, vacuolation, and fibrosis., Conclusions: The effect of crude extract and hexane soluble fraction of AH caused a significant reversal of gentamycin-induced nephrotoxicity., Competing Interests: The authors declare no conflict of interest. HK is serving as one of the Editorial Board members and Guest editors of this journal. We declare that HK had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to GP., (© 2023 The Author(s). Published by IMR Press.)

Over the last 20 years, granulocyte colony-stimulating factors (G-CSFs) have become the major therapeutic option for the treatment of patients with neutropenia. Most of the current G-CSFs require daily injections, which are inconvenient and expensive for patients. Increased understanding of G-CSFs' structure, expression, and mechanism of clearance has been very instrumental in the development of new generations of long-acting G-CSFs with improved efficacy. Several approaches to reducing G-CSF clearance via conjugation techniques have been investigated. PEGylation, glycosylation, polysialylation, or conjugation with immunoglobulins or albumins have successfully increased G-CSFs' half-lives. Pegfilgrastim (Neulasta) has been successfully approved and marketed for the treatment of patients with neutropenia. The rapidly expanding market for G-CSFs has increased demand for G-CSF biosimilars. Therefore, the importance of this review is to highlight the principle, elimination's route, half-life, clearance, safety, benefits, and limitations of different strategies and techniques used to increase the half-life of biotherapeutic G-CSFs. Understanding these strategies will allow for a new treatment with more competitive manufacturing and lower unit costs compared with that of Neulasta., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Theyab, Alsharif, Alzahrani, Oyouni, Hawsawi, Algahtani, Alghamdi and Alshammary.)

Schizophrenia (SCZ), a multifactorial neuropsychiatric disorder, is treated with inefficient antipsychotics and linked to poor treatment outcomes. This study, therefore, investigated the combined administration of prodigiosin (PDG) and selenium (Na 2 SeO 3 ) against SCZ induced by amphetamine (AMPH) in rats. Animals were allocated into four groups corresponding to their respective 7-day treatments: control, AMPH (2 mg/kg), PDG (300 mg/kg) + Na 2 SeO 3 (2 mg/kg), and AMPH + PDG + Na 2 SeO 3 . The model group exhibited biochemical, molecular, and histopathological changes similar to those of the SCZ group. Contrastingly, co-administration of PDG and Na 2 SeO 3 significantly increased the time for social interaction and decreased AChE and dopamine. It also downregulated the gene expression of NMDAR1 and restored neurotrophin (BDNF and NGF) levels. Further, PDG combined with Na 2 SeO 3 improved the antioxidant defence of the hippocampus by boosting the activities of SOD, CAT, GPx, and GR. These findings were accompanied by an increased GSH, alongside decreased MDA and NO levels. Furthermore, schizophrenic rats having received PDG and Na 2 SeO 3 displayed markedly lower IL-1β and TNF-α levels compared to the model group. Interestingly, remarkable declines in the Bax (pro-apoptotic) and increases in Bcl-2 (anti-apoptotic) levels were observed in the SCZ group that received PDG and Na 2 SeO 3 . The hippocampal histological examination confirmed these changes. Collectively, these findings show that the co-administration of PDG and Na 2 SeO 3 may have a promising therapeutic effect for SCZ. This is mediated by mechanisms related to the modulation of cholinergic, dopaminergic, and glutaric neurotransmission and neurotrophic factors, alongside the suppression of oxidative damage, neuroinflammation, and apoptosis machinery., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Curcumin has been isolated from the rhizomes of Curcuma longa. Over the years, it has shown outstanding therapeutic potential in various human disorders, including cancers., Objective: The aim is to study curcumin's effects on the apoptosis signaling pathway in the head and neck squamous cell carcinoma (HNSCC) cell line HN5., Methods: The cytotoxicity of curcumin on HN5 cells were assessed. In addition, HN5 cells were also treated with curcumin to evaluate its effect on the caspase-8, -9, Bcl-2, Bax, and Stat3 gene expressions., Results: The results exhibited that cell viability reduced following curcumin treatment in a concentration- dependent manner. Curcumin treatment caused decreased expression of Bcl2, with simultaneous upregulation of the Bax/Bcl2 ratio. Curcumin increased caspase-9 expression, did not affect caspase-8, and decreased Stat3 expression. The induction of the mitochondria-dependent apoptosis pathway of curcumin happened by modulating the expression of Bcl2 and Bax genes, resulting in the caspase-9 activation. Furthermore, curcumin decreased the expression of the Stat3 in HN-5 cells., Conclusions: In conclusion, curcumin showed marked anticancer effects in the HN-5 cell line by modulating Stat-3; Bax/Bcl-2 expression in vitro., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The COVID-19 pandemic has been the focus of research the past two years. The major breakthrough was made by discovering pathways related to SARS-CoV-2 infection through cellular interaction by angiotensin-converting enzyme (ACE2) and cytokine storm. The presence of ACE2 in lungs, intestines, cardiovascular tissues, brain, kidneys, liver, and eyes shows that SARS-CoV-2 may have targeted these organs to further activate intracellular signalling pathways that lead to cytokine release syndrome. It has also been reported that SARS-CoV-2 can hijack coatomer protein-I (COPI) for S protein retrograde trafficking to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC), which, in turn, acts as the assembly site for viral progeny. In infected cells, the newly synthesized S protein in endoplasmic reticulum (ER) is transported first to the Golgi body, and then from the Golgi body to the ERGIC compartment resulting in the formation of specific a motif at the C-terminal end. This review summarizes major events of SARS-CoV-2 infection route, immune response following host-cell infection as an important factor for disease outcome, as well as comorbidity issues of various tissues and organs arising due to COVID-19. Investigations on alterations of host-cell machinery and viral interactions with multiple intracellular signaling pathways could represent a major factor in more effective disease management., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

COVID-19 is a worldwide pandemic caused by SARS-coronavirus-2 (SARS-CoV-2). Less than a year after the emergence of the Covid-19 pandemic, many vaccines have arrived on the market with innovative technologies in the field of vaccinology. Based on the use of messenger RNA (mRNA) encoding the Spike SARS-Cov-2 protein or on the use of recombinant adenovirus vectors enabling the gene encoding the Spike protein to be introduced into our cells, these strategies make it possible to envisage the vaccination in a new light with tools that are more scalable than the vaccine strategies used so far. Faced with the appearance of new variants, which will gradually take precedence over the strain at the origin of the pandemic, these new strategies will allow a much faster update of vaccines to fight against these new variants, some of which may escape neutralization by vaccine antibodies. However, only a vaccination policy based on rapid and massive vaccination of the population but requiring a supply of sufficient doses could make it possible to combat the emergence of these variants. Indeed, the greater the number of infected individuals, the faster the virus multiplies, with an increased risk of the emergence of variants in these RNA viruses. This review will discuss SARS-CoV-2 pathophysiology and evolution approaches in altered transmission platforms and emphasize the different mutations and how they influence the virus characteristics. Also, this article summarizes the common vaccines and the implication of the mutations and genetic variety of SARS-CoV-2 on the COVID-19 biomedical arbitrations., Competing Interests: Conflict of interest statement The authors declare they have no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Mucormycosis is an infection caused by fungi belonging to the order Mucorales. Rhizopus oryzae is one of the most prevalent organisms identified in mucormycosis patients. Because it spreads quickly through the blood vessels, this opportunistic illness has an exceptionally high fatality rate, even when vigorous treatment is administered. Nonetheless, it has a high tolerance to antifungal medicines, limiting treatment options. As a result, improved methods for preventing and treating mucormycosis are desperately needed. Hence, this study was aimed at assessing the effect of lupeol, quercetin, and solasodine against mucormycosis based on computational approaches., Methods: The Rhizopus oryzae RNA-dependent RNA polymerase (RdRp) was the target for the design of drugs against the deadly mucormycosis. The three-dimensional structure of the RdRp was modelled with a Swiss model and validated using PROCHECK, VERIFY 3D, and QMEAN. Using the Schrodinger maestro module, a molecular docking study was performed between RdRp and the antimicrobial phytochemicals lupeol, quercetin, and solasodine. A molecular dynamics (MD) simulation study was used to assess the stability and interaction of the RdRp with these phytochemicals., Results: The RdRp protein binds strongly to lupeol (-7.2 kcal/mol), quercetin (-9.1 kcal/mol), and solasodine (-9.6 kcal/mol), according to molecular docking assessment based on the lowest binding energy, confirmation, and bond interaction. Simulations suggest that lupeol, quercetin, and solasodine complexes with RdRp and showed stable confirmation with minimal fluctuation throughout the 200 nanoseconds based on the RMSD and RMSF trajectory assessments., Conclusion: The molecular docking and MD simulation investigation improved our understanding of phytochemical-RdRp interactions. Due to its high affinity for RdRp, solasodine may be a better treatment option for mucormycosis., Competing Interests: Conflict of interest None., (Copyright © 2022. Published by Elsevier Ltd.)

Infectious diseases continue to be a leading cause of morbidity and mortality worldwide. The majority of infectious diseases are caused by intracellular pathogenic bacteria (IPB). Historically, conventional vaccination drives have helped control the pathogenesis of intracellular bacteria and the emergence of antimicrobial resistance, saving millions of lives. However, in light of various limitations, many diseases that involve IPB still do not have adequate vaccines. In response to increasing demand for novel vaccine development strategies, a new area of vaccine research emerged following the advent of genomics technology, which changed the paradigm of vaccine development by utilizing the complete genomic data of microorganisms against them. It became possible to identify genes related to disease virulence, genetic patterns linked to disease virulence, as well as the genetic components that supported immunity and favorable vaccine responses. Complete genomic databases, and advancements in transcriptomics, metabolomics, structural genomics, proteomics, immunomics, pan-genomics, synthetic genomics, and population biology have allowed researchers to identify potential vaccine candidates and predict their effects in patients. New vaccines have been created against diseases for which previously there were no vaccines available, and existing vaccines have been improved. This review highlights the key issues and explores the evolution of vaccines. The increasing volume of IPB genomic data, and their application in novel genome-based techniques for vaccine development, were also examined, along with their characteristics, and the opportunities and obstacles involved. Critically, the application of genomics technology has helped researchers rapidly select and evaluate candidate antigens. Novel vaccines capable of addressing the limitations associated with conventional vaccines have been developed and pressing healthcare issues are being addressed.

The rhizomatous plant turmeric, which is frequently used as a spice and coloring ingredient, yields curcumin, a bioactive compound. Curcumin inhibits platelet activation and aggregation and improves platelet count. Platelets dysfunction results in several disorders, including inflammation, atherothrombosis, and thromboembolism. Several studies have proved the beneficial role of curcumin on platelets and hence proved it is an important candidate for the treatment of the aforementioned diseases. Moreover, curcumin is also frequently employed as an anti-inflammatory agent in conventional medicine. In arthritic patients, it has been shown to reduce the generation of pro-inflammatory eicosanoids and to reduce edema, morning stiffness, and other symptoms. Curcumin taken orally also reduced rats' acute inflammation brought on by carrageenan. Curcumin has also been proven to prevent atherosclerosis and platelet aggregation, as well as to reduce angiogenesis in adipose tissue. In the cerebral microcirculation, curcumin significantly lowered platelet and leukocyte adhesion. It largely modulated the endothelium to reduce platelet adhesion. Additionally, P-selectin expression and mice survival after cecal ligation and puncture were improved by curcumin, which also altered platelet and leukocyte adhesion and blood-brain barrier dysfunction. Through regulating many processes involved in platelet aggregation, curcuminoids collectively demonstrated detectable antiplatelet activity. Curcuminoids may therefore be able to prevent disorders linked to platelet activation as possible therapeutic agents. This review article proposes to highlight and discuss the regulatory effects of curcumin on platelets.

Objectives: This study was conducted to evaluate the levels of salivary uric acid and arginase in patients with periodontitis, generalized gingivitis, and in healthy individuals. Then, the effects of non-surgical periodontal therapy on levels of salivary arginase and uric acid were also investigated., Methods: A total of 60 subjects were divided into three groups based on periodontal health: group I comprised 20 healthy individuals; group II comprised 20 subjects who had generalized gingivitis; group III comprised 20 subjects who had generalized periodontitis. On day 0, the clinical examination of periodontal status was recorded, following which saliva samples were collected. Group II and group III subjects underwent non-surgical periodontal therapy. These patients were recalled on day 30 to collect saliva samples. The periodontal parameters were reassessed on day 90, and saliva samples were collected for analysis of salivary arginase and uric acid levels., Results: Group II and group III showed improvement in clinical parameters following non-surgical periodontal therapy on the 90th day. The MGI score, PPD, and CAL showed improvement. On day 0, at baseline, salivary arginase levels in group III and group II were higher than those in healthy subjects, whereas on day 0, salivary uric acid levels in group III and group II were lower than those in healthy subjects. Both on day 0 and day 90, the salivary arginase level showed a positive correlation with the periodontal parameters, whereas the salivary uric acid level was positively correlated with the periodontal parameters on day 90., Conclusion: the level of salivary arginase was a pro-inflammatory marker and a raised level of salivary uric acid was an anti-inflammatory marker following periodontal therapy, suggesting their pivotal role in assessing periodontal status and evaluation of treatment outcome.

Aim: Orthodontic literature is scant when it comes to microbial corrosion. The oral prevalence of many bacteria which are capable of causing microbial corrosion is reported in the dental literature. The aim of this study is to experimentally determine the corrosive potential of an oral strain of Sulfate-reducing bacteria., Materials and Methods: Stainless steel (SS) bracket, stainless steel archwire, NiTi archwire, Titanium molybdenum (TMA) archwire, and titanium miniscrew were immersed in five media which included Artificial saliva (group I), Sulfate rich artificial saliva (group II), API agar medium specific for SRB (group III), AS + API medium+ bacterial strain (group IV), SRAS+ API medium+ bacterial strain (group V). The materials were then subjected to Scanning electron microscopy and energy-dispersive X-ray analysis (EDX)., Results: Materials in groups I, II, and III did not show any surface changes whereas materials in groups IV and V which contained the bacteria showed surface changes which were erosive patches suggestive of corrosion. EDX analyses were in line with similar findings., Conclusion: This in vitro study suggested that the oral strain of Sulfate-reducing bacteria was able to induce corrosive changes in the experimental setup.

Cancer is one of the most severe medical conditions in the world, causing millions of deaths each year. Chemotherapy and radiotherapy are critical for treatment approaches, but both have numerous adverse health effects. Furthermore, the resistance of cancerous cells to anticancer medication leads to treatment failure. The rising burden of cancer requires novel efficacious treatment modalities. Natural remedies offer feasible alternative options against malignancy in contrast to available synthetic medication. Selective killing of cancer cells is privileged mainstream in cancer treatment, and targeted therapy represents the new tool with the potential to pursue this aim. The discovery of innovative therapies targeting essential components of DNA damage signaling and repair pathways such as ataxia telangiectasia mutated and Rad3 related Checkpoint kinase 1 (ATR-CHK1)has offered a possibility of significant therapeutic improvement in oncology. The activation and inhibition of this pathway account for chemopreventive and chemotherapeutic activity, respectively. Targeting this pathway can also aid to overcome the resistance of conventional chemo- or radiotherapy. This review enlightens the anticancer role of natural products by ATR-CHK1 activation and inhibition. Additionally, these compounds have been shown to have chemotherapeutic synergistic potential when used in combination with other anticancer drugs. Ideally, this review will trigger interest in natural products targeting ATR-CHK1 and their potential efficacy and safety as cancer lessening agents., Competing Interests: Conflict of Interest Statement 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 © 2022. Published by Elsevier Masson SAS.)

BACKGROUND In this study, we aimed to evaluate orthodontic mini-implant placement in the maxillary anterior alveolar region by cone beam computed tomography (CBCT) in 15 patients at a single center in South India. MATERIAL AND METHODS A total of 15 CBCT scans of orthodontic patients after completion of leveling and aligning stage were included. The thickness of labial alveolar bone, labio-palatal bone, and inter-radicular distance between the maxillary central incisors (U1-U1), maxillary central and lateral incisor (U1-U2), and maxillary lateral incisor and canine (U2-U3) at vertical levels 4 mm, 6 mm, and 8 mm above the interdental cementoenamel junction were measured. Descriptive statistics, ANOVA, and Tukey post hoc tests were done to assess the differences among the groups. An independent t test was done to analyze differences by sex. RESULTS The thickness of cortical bone in the labial region was higher in the U2-U3 site than in the U1-U1 site, at a height of 4 mm. Also, there was a significant difference between 4 mm and 8 mm heights in the U2-U3 region. No significant difference was noted in bone dimensions among men and women and in the labio-palatal bone thickness among the different sites. The inter-radicular distance was the highest between the U2-U3 site, while it was the lowest in the U1-U2 site. CONCLUSIONS The findings from this center showed that when CBCT was used to evaluate orthodontic mini-implant placement in the maxillary anterior alveolar region, the U2-U3 and U1-U1 locations at heights between 6 mm to 8 mm apical to the interdental cementoenamel junction were optimal for placement of the mini-implants.

Background and Objective : Staphylococcus epidermidis is an opportunistic pathogen from pediatric bacteremia that is commonly isolated. Biofilm is the major virulence factor of S. epidermidis ; however, the role of biofilm determinants in biofilm formation is highly contradictory and diverse. The current study aimed to investigate the role of polysaccharide-dependent and polysaccharide-independent pathogenic determinants in biofilm formation under physiological stress conditions. Materials and Methods : The isolates ( n = 75) were identified and screened for the icaADBC operon, IS256, and an array of MSCRAMMs (Microbial Surface Component Recognizing Adhesive Matrix Molecules) through PCR analysis. The activity of the icaADBC operon was detected by Congo red assay, and the biofilm formation was analyzed through microtiter plate assay. Results : S. epidermidis isolates produced biofilm ( n = 65; 86.6%) frequently. The icaA was the major representative module of the actively expressing icaADBC operon ( n = 21; 80.7% sensitivity). The MSCRAMMs, including fbe ( n = 59; 90.7%; p = 0.007), and embp ( n = 57; 87.6%; p = 0.026), were highly prevalent and associated with biofilm positive S. epidermidis . The prevalence of icaADBC operon in biofilm positive and negative S. epidermidis was not significant ( n = 41; 63%; p = 0.429). No significant association was found between IS256 and actively complete icaADBC operon ( n = 10; 47.6%; p = 0.294). In the presence of 5% human plasma and glucose stress, S. epidermidis produced a strong biofilm ( n = 55; 84.6%). Conclusion : The polysaccharide-dependent biofilm formation is significantly replaced ( n = 21; 28%; p = 0.149) by a polysaccharide-independent mechanism ( n = 59; 90.7%; p = 0.007), in which the MSCRAMMs might actively play their role. The fibrinogen-binding protein and extracellular matrix-binding protein might be potential anti-biofilm drug targets, markers of rapid diagnosis, and potential vaccine candidates of S. epidermidis involved in pediatric bacteremia.

Previous studies have demonstrated the beneficial effects of melatonin in diabetic rats. However, limited studies have been conducted on the potential effects of melatonin on the descriptive histopathological and morphometric findings in different compartments of the adrenal glands in diabetic animal models. In this study, using a streptozotocin (STZ)-induced diabetic rat model, we sought to examine histological alterations in the pancreas and adrenal glands and observe the effect of the administration of melatonin on the histopathology and morphology of the pancreas and the adrenal gland cortex and medulla that are altered by STZ-induced hyperglycemia. Rats were randomly assigned to four different groups: Group I, normal control; Group II, melatonin group (MT) (10 mg/kg/day); Group III, (diabetic STZ group), and Group IV, diabetic (STZ) + melatonin group (MT). Throughout the experiment, the animals' fasting blood sugar levels were measured. Blood was obtained to determine the animals' cumulative blood sugar levels after sacrification. For histological and morphometrical evaluations, the pancreatic and adrenal gland tissues were dissected and processed. Our results showed that diabetic rats receiving melatonin significantly ( P < 0.05) improved their fasting blood sugar and cumulative blood sugar levels compared to the diabetic group not receiving melatonin. Furthermore, histopathological examinations of the pancreatic and adrenal tissues of the diabetic rats indicated the occurrence of severe histopathological and morphometric changes. Morphometric analysis of the adrenals indicated a significant increase ( P < 0.05) in the thickness of the cortex zones [zona glomerulosa (ZG), zona fasciculata (ZF), and zona reticularis (ZR)] for the diabetic STZ group compared with other groups, and a significant decrease ( P < 0.05) in the diameter of the in adrenal gland medullas in the diabetic STZ rats compared to the other groups. Furthermore, treatment with melatonin restored these changes in both the pancreatic and adrenal gland tissues and produced a significant ( P < 0.05) improvement in the cortex and medulla thickness compared to the untreated diabetic rats. Overall, melatonin significantly reduced the hyperglycemic levels of glucose in diabetic rats and reversed the majority of histopathological alterations in the tissues of the pancreas and adrenals, demonstrating its anti-diabetic activity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Oyouni, Al-Amer, Ali, Altayar, Jalal, Albalawi, Abuderman, Alsharif, AlZamzami, Albrakati and Elmahallawy.)

Guided bone regeneration (GBR) is a reliable technique used to treat ridge deficiencies prior or during implant placement. Injectable-platelet rich fibrin (i-PRF) laced with a bone substitute (sticky bone) has heralded the way for advancing the outcomes of bone regeneration. This study evaluated the efficacy of sticky bone in horizontal ridge augmentation with and without collagen membrane. A total of 20 partially edentulous patients (Group-I n = 10; Group-II n = 10) that indicated GBR were included, and the surgical procedure was carried out. In Group-I, the sticky bone and collagen membrane were placed in ridge-deficient sites and Group-II received only sticky bone. At the end of 6 months, 20 patients (Group-I (n = 10); Group-II (n = 10)) completed the follow-up period. A CBCT examination was performed to assess changes in the horizontal ridge width (HRW) and vertical bone height (VBH). A statistically significant increase in HRW (p < 0.05) was observed in both groups with mean gains of 1.35 mm, 1.55 mm, and 1.93 mm at three levels (crest, 3 mm, and 6 mm) in Group-I and 2.7 mm, 2.8 mm, and 2.6 mm at three levels in Group-II. The intergroup comparison revealed statistical significance (p < 0.05) with respect to HRW and KTW (Keratinised tissue width) gains of 0.775 at the 6-month follow-up. Sticky-bone (Xenogenic-bone graft + i-PRF) served as a promising biomaterial in achieving better horizontal bone width gain.