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Sabah Ansar,1 Saad M Alshehri,2 Manal Abudawood,1 Sherifa S Hamed,3,4 Tansir Ahamad2 1Clinical Laboratory Sciences, Applied Medical Science, King Saud University, Riyadh, Saudi Arabia; 2Department of Chemistry, College of Science, King Saud University, Riyadh, Saudi Arabia; 3Zoology Department, College of Science, King Saud University, Riyadh, Saudi Arabia; 4Zoology Department, Faculty of Science, University of Alexandria, Moharram Bey, Alexandria, Egypt Abstract: Silver nanoparticles (AgNPs) have attracted the most interest in terms of their potential biomedical and industrial applications. However, these nanoparticles have shown their toxic behavior toward environment, living tissues, and organisms. Selenium (Se), an essential trace element, is necessary for various metabolic processes, including protection against ­oxidative stress and immune function. The present study was undertaken to evaluate the effect of Se against AgNP-induced hepatic oxidative stress. AgNPs were synthesized and then prepared nanoparticles were characterized using various analytical techniques such as UV-visible spectroscopy, X-ray diffraction, and transmission electron microscopy. Rats were administered AgNPs intraperitoneally (5 mg/kg/day) and Se (0.2 mg/kg) was given by gavage. AgNP administration induced hepatic damage as indicated by the serum marker enzymes with reduction in levels of glutathione, and decrease in activities of SOD, CAT, and GSH-peroxidase (P

Ansar S, Alshehri SM, Abudawood M, Hamed SS, Ahamad T. Antioxidant and hepatoprotective role of sele-nium against silver nanoparticles. Int J Nanomedicine. 2017;12:7789–7797. On page 7796, the Acknowledgment is incorrect, it should have been: The authors extend their appreciation to the Deanship of Scientific Research, King Saud University, for funding this work through the Undergraduate Student Research Support Program. Read the original article.

On November 14, 2022, the FDA granted accelerated approval to mirvetuximab soravtansine-gynx for treatment of adult patients with folate receptor-α (FRα)-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received one to three prior systemic therapies. The VENTANA FOLR1 (FOLR-2.1) RxDx Assay was approved as a companion diagnostic device to select patients for this indication. Approval was based on Study 0417 (SORAYA, NCT04296890), a single-arm, multicenter trial. In 104 patients with measurable disease who received mirvetuximab soravtansine-gynx, the overall response rate was 31.7% [95% confidence interval (CI), 22.9-41.6] with a median duration of response of 6.9 months (95% CI, 5.6-9.7). Ocular toxicity was included as a Boxed Warning in the U.S. Prescribing Information (USPI) to alert providers of the risks of developing severe ocular toxicity including vision impairment and corneal disorders. Pneumonitis and peripheral neuropathy were additional important safety risks included as Warnings and Precautions in the USPI. This is the first approval of a targeted therapy for FRα-positive, platinum-resistant ovarian cancer and the first antibody-drug conjugate approved for ovarian cancer. This article summarizes the favorable benefit-risk assessment leading to FDA's approval of mirvetuximab soravtansine-gynx., (©2023 American Association for Cancer Research.)

On August 13, 2021, the FDA approved belzutifan (WELIREG, Merck), a first-in-class hypoxia-inducible factor (HIF) inhibitor for adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery. The FDA granted approval based on the clinically meaningful effects on overall response rate (ORR) observed in patients enrolled in Study MK-6482-004. All 61 patients had VHL-associated RCC; some also had CNS hemangioblastomas and/or pNET. For VHL disease-associated RCC, ORR was 49% [95% confidence interval (CI), 36-62], median duration of response (DoR) was not reached, 56% of responders had DoR ≥12 months, and median time to response was 8 months. Twenty-four patients had measurable CNS hemangioblastomas with an ORR of 63% (95% CI, 41-81), and 12 patients had measurable pNET with an ORR of 83% (95% CI, 52-98). For these tumors, median DoR was not reached, with 73% and 50% of patients having response durations ≥12 months for CNS hemangioblastomas and pNET, respectively. The most common adverse reactions, including laboratory abnormalities, reported in ≥20% were anemia, fatigue, increased creatinine, headache, dizziness, increased glucose, and nausea. Belzutifan can render some hormonal contraceptives ineffective and can cause embryo-fetal harm during pregnancy. This article summarizes the data and the FDA thought process supporting traditional approval of belzutifan for this indication., (©2022 American Association for Cancer Research.)

On June 15, 2020, the FDA granted accelerated approval to lurbinectedin for the treatment of adult patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. Approval was granted on the basis of the clinically meaningful effects on overall response rate (ORR) and duration of response (DOR), and the safety profile observed in a multicenter, open-label, multicohort clinical trial (PM1183-B-005-14, NCT02454972), referred to as Study B-005, in patients with advanced solid tumors. The trial included a cohort of 105 patients with metastatic SCLC who had disease progression on or after platinum-based chemotherapy. The confirmed ORR determined by investigator assessment using RECIST 1.1 in the approved SCLC patient population was 35% [95% confidence interval (CI): 26-45], with a median DOR of 5.3 (95% CI: 4.1-6.4) months. The drug label includes warnings and precautions for myelosuppression, hepatotoxicity, and embryo-fetal toxicity. This is the first drug approved by the FDA in over 20 years in the second line for patients with metastatic SCLC. Importantly, this approval includes an indication for patients who have platinum-resistant disease, representing an area of particular unmet need., (©2020 American Association for Cancer Research.)

On April 22, 2020, the FDA granted accelerated approval to sacituzumab govitecan-hziy (TRODELVY; Immunomedics, Inc.) for the treatment of patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease. Approval was based on data from the IMMU-132-01 trial, a single-arm, multicohort, multicenter, phase I/II trial of sacituzumab govitecan. The assessment of efficacy was based on 108 patients with mTNBC who had previously received at least two prior lines of therapy in the metastatic setting and who received sacituzumab govitecan 10 mg/kg i.v. The assessment of safety was based on 408 patients with advanced solid tumors who had received sacituzumab govitecan at doses up to 10 mg/kg i.v. The primary efficacy endpoint was investigator-assessed objective response rate (ORR) and duration of response (DoR) was a key secondary endpoint. The ORR was 33.3% [36/108; 95% confidence interval (CI), 24.6-43.1], and median DoR among responders was 7.7 months (95% CI, 4.9-10.8). The most common adverse reactions occurring in ≥25% of patients were nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia, constipation, rash, decreased appetite, and abdominal pain. This article summarizes the FDA review process and data supporting the approval of sacituzumab govitecan., (©2020 American Association for Cancer Research.)

Background: The portunid crab Charybdis hellerii is an economically critical aquatic species in the Mediterranean region. Several investigators have reported scanning electron microscopy (SEM) observations on some crustacean's eggs' morphology. Going through the previous studies, knowledge regarding the morphology of C. hellerii . vitellogenic oocytes and spawned egg membranes are not available., Aims and Objectives: In the present study, an attempt has been made to describe the morphology and the structure of the membranes of vitellogenic oocytes and the newly spawned eggs to provide necessary information for further studies on the reproductive and evolutionary biology of the crab C. hellerii ., Materials and Methods: Samples of ripe pinkish orange ovaries of non-ovigarous females and the spawned incubated eggs of ovigerous females with orange and grey spawns were processed for scanning electron microscopy. The prepared samples were examined in a Zeiss DSM 940 scanning electron microscope., Results: The present SEM study revealed that, vitellogenic oocytes are highly packed with yolk inclusions, which appear to be embedded in a definite acellular matrix and surrounded by a distinct chorion, which is pierced by several pores. The follicle cells appear polygonal in shape and interconnected through thin lateral projections and strongly associated with vitellogenic oocytes. The brooded fertilized eggs are attached through a marked stalk (funiculus) and surrounded by three distinct envelopes, which showed specific ornamentations and variations in their surface topography. The outer envelope coarsely wrinkled, while the middle envelope showed finely wrinkled ornamentation, and the inner envelope appeared with its characteristic spongy, porous appearance., Conclusions: This study denotes a significant difference between mature vitellogenic oocytes inside the ripe ovary and the spawned ova. The differences have been shown in the structure and external ornamentation of their surrounding membranes. Unlike the vitellogenic oocytes, the spawned ova were surrounded by three distinct layers, which are differ in their surface architecture. Such membrane architecture is species specific characteristic and has been thought to be an adaptive feature for brooded fertilized eggs to survive from stressful environmental conditions., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Microscopy and Ultrastructure.)

Objectives: This study aims to explore the perceptions of different stakeholders about the privatisation of the Saudi health care system., Methods: Using a qualitative case study design, we interviewed 21 administrators and clinical staff of a public hospital in the Eastern Province of the KSA and analysed all official documents relevant to this study. The analysis followed a thematic approach to provide an in-depth interpretation of the data., Results: Our analysis generated three main themes. The first was pertinent to the changes in the governance structure, with gradually increased autonomy from the government. The second reflected the necessity to introduce accountability within hospitals. The third described the cooperative relationship among the E1-Cluster hospitals as well as its competitive relationship with the private sector., Conclusion: Our study demonstrates the interplay between newly introduced concepts of autonomy and accountability within the Saudi health care system. The findings of this study and their implications for research, practice, and policy are elaborated. Such an understanding is essential to improve the implementation process of privatisation and to recognise new dynamics that are shaping the health care system. The study contributes to the current scarce literature on health care reforms in KSA by reporting perceptions and experiences of key stakeholders., (© 2020 The Authors.)

The human dentition is a typical diphyodont mammalian system with tooth replacement of most positions. However, after dental replacement and sequential molar development, the dental lamina undergoes apoptosis and fragments, leaving scattered epithelial units (dental lamina rests; DLRs). DLRs in adult humans are considered inactive epithelia, thought to possess limited capacity for further regeneration. However, we show that these tissues contain a small proportion of proliferating cells (assessed by both Ki67 and PCNA) but also express a number of common dental stem cell markers (Sox2, Bmi1, β-catenin and PH3) similar to that observed in many vertebrates that actively, and continuously regenerate their dentition. We compared these human tissues with the dental lamina of sharks that regenerate their dentition throughout life, providing evidence that human tissues have the capacity for further and undocumented regeneration. We also assessed cases of human ameloblastoma to characterise further the proliferative signature of dental lamina rests. Ameloblastomas are assumed to derive from aberrant lamina rests that undergo changes, which are not well understood, to form a benign tumour. We suggest that dental lamina rests can offer a potential source of important dental stem cells for future dental regenerative therapy. The combined developmental genetic data from the shark dental lamina and ameloblastoma may lead to the development of novel methods to utilise these rested populations of adult lamina stem cells for controlled tooth replacement in humans.

Background: Nanoparticles are widely utilized in many products such as cosmetics and sunscreens. The present study was undertaken to evaluate the effect of hesperidin (HSP) on nano zinc oxide particles (nZnO) induced oxidative stress in rat livers., Methods: Rats were randomly divided into 4 groups of 6 rats each and exposed to single administration of nZnO intraperitoneally (600 mg/kg bwt) and HSP (100 mg/kg bwt) by gavage. Group I served as the control; group II was given nZnO only; groups III received HSP only and group IV received nZnO 1 h after pretreatment with HSP for 7 days., Results: Compared to the controls, nZnO administration enhanced alanine aminotransferase (AST) and aspartate aminotransferase (ALT) levels (p < 0.05) with reduction in the levels of glutathione (GSH), catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) and increase in levels of malondialdehyde (MDA) while HSP attenuated nZnO-induced hepatotoxicity for above mentioned parameters., Conclusions: The induced toxicity in the liver was corrected by pretreatment with HSP. The findings of this study suggest that HSP pretreatment can potentially be used to prevent nZnO-induced biochemical alterations toxicity. Further, protection by HSP on biochemical results was confirmed by histopathological changes. The present study suggests that HSP can protect against nZnO-induced oxidative damage in the rat livers.

Background: Liver diseases are major global health problems. Ginseng extract has antioxidant, immune-modulatory and anti-inflammatory activities. This study investigated the effect of ginseng extract on carbon tetrachloride (CCl4)-induced liver fibrosis in rats., Methods: Male Wistar rats were divided into four groups: control group, ginseng group, CCl 4 group and CCl 4  + ginseng group. Liver injury was induced by the intraperitoneal (I.P) injection of 3 ml/kg CCl 4 (30% in olive oil) weekly for 8 weeks. The control group was I.P injected with olive oil. The expression of genes encoding transforming growth factor beta (TGF-β), type I TGF-β receptor (TβR-1), type II TGF-β receptor (TβR-II), mothers against decapentaplegic homolog 2 (Smad2), Smad3, Smad4, matrix metalloproteinase 2 (MMP2), MMP9, tissue inhibitor matrix metalloproteinase-1 (TIMP-1), Collagen 1a2 (Col1a2), Collagen 3a1 (Col3a1), interleukin-8 (IL-8) and interleukin -10 (IL-10) were measured by real-time PCR., Results: Treatment with ginseng extract decreased hepatic fat deposition and lowered hepatic reticular fiber accumulation compared with the CCl 4 group. The CCl 4 group showed a significant increase in hepatotoxicity biomarkers and up-regulation of the expression of genes encoding TGF-β, TβR-I, TβR-II, MMP2, MMP9, Smad-2,-3, -4, and IL-8 compared with the control group. However, CCl 4 administration resulted in the significant down-regulation of IL-10 mRNA expression compared with the control group. Interestingly, ginseng extract supplementation completely reversed the biochemical markers of hepatotoxicity and the gene expression alterations induced by CCl 4 ., Conclusion: ginseng extract had an anti-fibrosis effect via the regulation of the TGF-β1/Smad signaling pathway in the CCl 4 -induced liver fibrosis model. The major target was the inhibition of the expression of TGF-β1, Smad2, and Smad3.

The strawberry (Fragaria ananassa) has been extensively used to treat a wide range of ailments in many cultures. The present study was aimed at evaluating the hepatoprotective effect of strawberry juice on experimentally induced liver injury in rats. To this end, rats were introperitoneally injected with carbon tetrachloride (CCl4) with or without strawberry juice supplementation for 12 weeks and the hepatoprotective effect of strawberry was assessed by measuring serum liver enzyme markers, hepatic tissue redox status and apoptotic markers with various techniques including biochemistry, ELISA, quantitative PCR assays and histochemistry. The hepatoprotective effect of the strawberry was evident by preventing CCl4-induced increase in liver enzymes levels. Determination of oxidative balance showed that strawberry treatment significantly blunted CCl4-induced increase in oxidative stress markers and decrease in enzymatic and non-enzymatic molecules in hepatic tissue. Furthermore, strawberry supplementation enhanced the anti-apoptotic protein, Bcl-2, and restrained the pro-apoptotic proteins Bax and caspase-3 with a marked reduction in collagen areas in hepatic tissue. These findings demonstrated that strawberry (F. ananassa) juice possessed antioxidant, anti-apoptotic and anti-fibrotic properties, probably mediated by the presence of polyphenols and flavonoids compounds.

Drug interactions due to efflux transporters may result in one drug increasing or decreasing the systemic exposure of a second drug. The potential for in vivo drug interactions is estimated through in vitro cell assays. Variability in in vitro parameter determination (e.g., IC₅₀ values) among laboratories may lead to different conclusions in in vivo interaction predictions. The objective of this study was to investigate variability in in vitro inhibition potency determination that may be due to calculation methods. In a Caco-2 cell assay, the absorptive and secretive permeability of digoxin was measured in the presence of spironolactone, itraconazole and vardenafil. From the permeability data, the efflux ratio and net secretory flux where calculated for each inhibitor. IC₅₀ values were then calculated using a variety of equations and software programs. All three drugs decreased the secretory transport of digoxin in a concentration-dependent manner while increasing digoxin's absorption to a lesser extent. The resulting IC₅₀ values varied according to the parameter evaluated, whether percent inhibition or percent control was applied, and the computational IC₅₀ equation. This study has shown that multiple methods used to quantitate the inhibition of drug efflux in a cell assay can result in different IC₅₀ values. The variability in the results in this study points to a need to standardize any transporter assay and calculation methods within a laboratory and to validate the assay with a set of known inhibitors and non-inhibitors against a clinically relevant substrate.

The present study was designed to investigate the neuropathological effect of the two carbamate pesticides: methomyl and methiocarb on the neurons of the buccal ganglia in the land snail Eobania vermiculata using topical application and baiting technique. Their in vivo effects on acetylcholinesterase (AChE, EC 3.1.1.7) activity were also investigated. Sublethal dose and concentration (1/4 LD(50) and 1/4 LC(50)) of both pesticides were used, and the experiment lasted for 14 days. Histopathological and ultrastuctural alterations in the buccal ganglia were more obvious after the baiting technique treatment than after the topical application method, and methomyl was found to be more toxic than methiocarb. These alterations included shrinkage of the perikarya of neurons, increased cytoplasmic basophilia, and extreme indentation of the plasma membrane. In addition, the nuclei appeared karyolitic, eccentric, and highly shrunken with an irregular nuclear envelope. The most outstanding symptom observed after topical application of methiocarb was a highly vacuolated cytoplasm with a peripheral increase in electron density associated with dense accumulations of free ribosomes. On the other hand, an increased number of lysosomes and autophagosomes were observed after topical application of methomyl. Mitochondrial damage, increased number of lipid droplets, and myelin figures were frequently observed in ganglia treated with either methomyl or methiocarb. Moreover, it was noticed that both compounds induced reductions in AChE activity. However, methomyl exhibited more potency in reducing AChE activity than methiocarb.