Gene Therapy for Neuropsychiatric Disorders: Potential Targets and Tools.

Neuropsychiatric disorders that affect the central nervous system cause considerable pressures on the health care system and have a substantial economic burden on modern societies. The present treatments based on available drugs are mostly ineffective and often costly. The molecular process of neuropsychiatric disorders is closely connected to modifying the genetic structures inherited or caused by damage, toxic chemicals, and some current diseases. Gene therapy is presently an experimental concept for neurological disorders. Clinical applications endeavor to alleviate the symptoms, reduce disease progression, and repair defective genes. Implementing gene therapy in inherited and acquired neurological illnesses entails the integration of several scientific disciplines, including virology, neurology, neurosurgery, molecular genetics, and immunology. Genetic manipulation has the power to minimize or cure illness by inducing genetic alterations at endogenous loci. Gene therapy that involves treating the disease by deleting, silencing, or editing defective genes and delivering genetic material to produce therapeutic molecules has excellent potential as a novel approach for treating neuropsychiatric disorders. With the recent advances in gene selection and vector design quality in targeted treatments, gene therapy could be an effective approach. This review article will investigate and report the newest and the most critical molecules and factors in neuropsychiatric disorder gene therapy. Different genome editing techniques available will be evaluated, and the review will highlight preclinical research of genome editing for neuropsychiatric disorders while also evaluating current limitations and potential strategies to overcome genome editing advancements.

Recent Advances in Anticancer Activity of Novel Plant Extracts and Compounds from Curcuma longa in Hepatocellular Carcinoma.

PURPOSE: Among all forms of cancers, hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. There are several treatment options for HCC ranging from loco-regional therapy to surgical treatment. Yet, there is high morbidity and mortality. Recent research focus has shifted towards more effective and less toxic cancer treatment options. Curcumin, the active ingredient in the Curcuma longa plant, has gained widespread attention in recent years because of its multifunctional properties as an antioxidant, anti-inflammatory, antimicrobial, and anticancer agent. METHODS: A systematic search of PubMed, Embase and Google Scholar was performed for studies reporting incidence of HCC, risk factors associated with cirrhosis and experimental use of curcumin as an anti-cancer agent. RESULTS: This review exclusively encompasses the anti-cancer properties of curcumin in HCC globally and it's postulated molecular targets of curcumin when used against liver cancers. CONCLUSIONS: This review is concluded by presenting the current challenges and future perspectives of novel plant extracts derived from C. longa and the treatment options against cancers.

A cross-sectional study of the impact of COVID-19 pandemic on the physical activity of Jordanian population.

Background: Since the declaration of the COVID-19 pandemic on 11th March 2020, the public health recommendations have applied lockdowns and restrictions to limit the spread of the disease. These measures determined outdoor activities and access to many forms of exercise. Objective: The primary objective of this study was to examine the impact of the COVID-19 pandemic on the physical activity (PA) of the Jordanian population. Methods: A cross-sectional online survey was designed using Google Forms services and distributed on social media platforms during the first two weeks of November 2020 to evaluate the exercise activity changes during the COVID-19 pandemic in the study population. In this research, we included those who perform any form of physical activity (n = 1103). The data collected were analyzed using the Statistical Package for the Social Sciences (SPSS) version 26 (IBM SPSS Corp, SPSS Statistics ver. 26, USA). The categorical variables were summarized as frequencies and proportions and were compared using the Chi-square. For all analyses, P-value less than 0.05 was considered statistically significant. Results: A total of 1103 out of 2,511 (43.9%) respondents who participated in the survey were physically exercising during the COVID-19 pandemic. 41.8% were exercising at an irregular frequency, while 21.5% were exercising daily, 16.8% were exercising three to five times a week, and 19.9% were exercising once or twice a week. Moreover, 282 (25.6%) respondents started doing some form of exercise during the pandemic. Those significantly were less than 18-year-old, male gender, were single, were non-smokers, and had a diploma or bachelor's degree in a health-related major. These changes in the level of exercise have been attributed by 57.8% of respondents to the health aspects where they realized the importance of exercising in strengthening the immune system against diseases, including COVID-19. Conclusion: The current study showed that lockdown, due to the COVID-19 pandemic, had a positive impact on the healthy lifestyle of the Jordanian population which was attributed to their feeling of the importance of sports practice on the immune system and the availability of time for those activities. However, the younger and individuals were more aware of the importance of these practices which highlights the importance of considering other age groups in future studies of healthy behaviors.

Effectiveness of interactive teaching intervention on medical students' knowledge and attitudes toward stem cells, their therapeutic uses, and potential research applications.

BACKGROUND: Stem cell science is rapidly developing with the potential to alleviate many non-treatable diseases. Medical students, as future physicians, should be equipped with the proper knowledge and attitude regarding this hopeful field. Interactive teaching, whereby the teachers actively involve the students in the learning process, is a promising approach to improve their interest, knowledge, and team spirit. This study aims to evaluate the effectiveness of an interactive teaching intervention on medical students' knowledge and attitudes about stem cell research and therapy. METHODS: A pre-post test study design was employed. A six-session interactive teaching course was conducted for a duration of six weeks as an intervention. Pre- and post-intervention surveys were used. The differences in the mean scores of students' knowledge and attitudes were examined using paired t-test, while gender differences were examined using an independent t-test. RESULTS: Out of 71 sixth-year medical students from different nationalities invited to participate in this study, the interactive teaching course was initiated by 58 students resulting in a participation rate of 81.7%. Out of 58 students, 48 (82.8%) completed the entire course. The mean age (standard deviation) of students was 24 (1.2) years, and 32 (66.7%) were males. The results showed poor knowledge about stem cells among the medical students in the pre-intervention phase. Total scores of stem cell-related knowledge and attitudes significantly improved post-intervention. Gender differences in knowledge and attitudes scores were not statistically significant post-intervention. CONCLUSIONS: Integrating stem cell science into medical curricula coupled with interactive learning approaches effectively increased students' knowledge about recent advances in stem cell research and therapy and improved attitudes toward stem cell research and applications.

Negative histology in surgically managed tubal ectopic pregnancy.

OBJECTIVE: To determine the rate of negative histology following salpingectomy for suspected ectopic pregnancy. METHODS: A retrospective case series in a university hospital in the southwest of England was carried out. The records of all patients who had a salpingectomy for suspected ectopic pregnancy between January 2007 and December 2012 were reviewed. The primary outcome was the histology result. RESULTS: In total, 359 salpingectomies were performed for suspected ectopic pregnancy over 6 years. On histologic examination, 4.7% of fallopian tubes did not have evidence of an implantation site or trophoblastic tissue. When the macroscopic appearance of the fallopian tube was correlated with the surgical findings (e.g., rupture with large hemoperitoneum) and follow-up notes were reviewed thoroughly, the histology of 0.84% of all salpingectomies was not consistent with a tubal ectopic pregnancy. CONCLUSIONS: True negative histology for surgically managed ectopic pregnancy is less than 1%.

Overview of key molecular and pharmacological targets for diabetes and associated diseases.

Diabetes epidemiological quantities are demonstrating one of the most important communities' health worries. The essential diabetic difficulties are including cardiomyopathy, nephropathy, inflammation, and retinopathy. Despite developments in glucose decreasing treatments and drugs, these diabetic complications are still ineffectively reversed or prohibited. Several signaling and molecular pathways are vital targets in the new therapies of diabetes. This review assesses the newest researches about the key molecules and signaling pathways as targets of molecular pharmacology in diabetes and diseases related to it for better treatment based on molecular sciences. The disease is not cured by current pharmacological strategies for type 2 diabetes. While several drug combinations are accessible that can efficiently modulate glycemia and mitigate long-term complications, these agents do not reverse pathogenesis, and in practice, they are not established to modify the patient's specific molecular profiling. Therapeutic companies have benefited from human genetics. Genome exploration, which is agnostic to the information that exists, has revealed tens of loci that impact glycemic modulation. The physiological report has begun to examine subtypes of diseases, illustrate heterogeneity and propose biochemical therapeutic pathways.

Stem cell-related knowledge and attitudes among physicians in Jordan.

BACKGROUND: Rapid advancement of stem cell (SC) therapies provides both opportunities and risks for patients and physicians alike. Physicians have a role in counselling patients about unproven SC therapies, requiring a basic level of knowledge and access to information about SCs. OBJECTIVE: This study sought to assess SC-related knowledge of and attitudes among physicians in Jordan to elucidate areas of deficiency that can be addressed. METHODS: A cross-sectional survey, comprising questions on demographics and SC knowledge and attitudes, was designed as a scoring system to evaluate physicians' knowledge and attitudes. Participants were recruited from 10 major hospitals in Jordan over 3 months between February and April 2019. The internal consistency of the scoring scales was calculated using Cronbach's alpha reliability coefficient. Gender differences were evaluated with an independent t-test. RESULTS: In total, 382 physicians in Jordan completed the survey (59.9% response rate). They demonstrated a low/moderate level of overall SC knowledge (51.3%), but most lacked confidence in their ability to answer patients' questions about SC therapies (64.7%). However, the total attitude score was moderate/high positive (66.8%) and most were interested in learning more about SCs (80.8%). Male physicians reported significantly more knowledge than females (P < .0001). CONCLUSIONS: This study reveals Jordanian physicians' hesitancy to counsel patients about SC therapies, largely because of gaps in knowledge. However, overall attitudes toward SC research and therapies are positive. The results of this study demonstrate a need to cover SC-related information in medical curricula in Jordan, as well as to support initiatives to regulate SC tourism in Jordan.

Polymorphic Variants in 5'-UTR Regions of the RAD51 Gene are Associated With RAD51 Expression and Triple-Negative Breast Cancer (TNBC): A Case-Control Study.

Breast cancer is a heterogeneous disease at morphologic and molecular levels, which is considered the most commonly occurring cancer in women. RAD51, a DNA-repairing protein, involves homologous recombination and has a vital role in genome stability. Polymorphism of the RAD51 gene, and its overexpression, has been proposed to be associated with the development of breast cancer. Overexpression of RAD51 in many types of human cancer including metastatic breast cancer may signify its potential use as a biomarker. Considering the numerous reports on the role of the 5'-UTR-RAD51 polymorphism in breast cancer, this study aimed to investigate the utility of RAD51 gene expression and its variants G135C and G172T as a possible foretelling factor of breast cancer development. DNA sequencing and immunohistochemistry of RAD51 were conducted on 103 samples from patients diagnosed with sporadic breast cancer and 80 samples from a control group. The results demonstrated that the RAD51 variants, G135C and G172T, were significantly presented in the breast cancer tissue compared with the control group. RAD51 expression was mainly shown in the cytoplasm of malignant cells (56% of cases) and significantly correlated with p53 and G135C, C135C variants. Moreover, the occurrence of the G172T variant was significantly associated with the expression of estrogen receptor. Interestingly, 21/26 (81%) of the triple-negative breast cancer showed G135C and C135C genotypes that were significantly associated with the expression of RAD51 (73%). In conclusion, the G135C and C135C variants together with the cytoplasmic expression of RAD51 may have clinical potential as a prognostic predictor for breast cancer development and aggressiveness.

A Potential MRI Agent and an Anticancer Drug Encapsulated within CPMV Virus-Like Particles.

BACKGROUND: Virus nanoparticles have been extensively studied over the past decades for theranostics applications. Viruses are well-characterized, naturally occurring nanoparticles that can be produced in high quantity with a high degree of similarity in both structure and composition. OBJECTIVES: The plant virus Cowpea Mosaic Virus (CPMV) has been innovatively used as a nanoscaffold. Utilization of the internal cavity of empty Virus-Like Particles (VLPs) for the inclusion of therapeutics within the capsid has opened many opportunities in drug delivery and imaging applications. METHODS: The encapsidation of magnetic materials and anticancer drugs was achieved. SuperscriptCPMV denotes molecules attached to the external surface of CPMV and CPMVSubscript denotes molecules within the interior of the capsid. RESULTS: Here, the generation of novel VLPs incorporating iron-platinum nanoparticles TCPMVFePt and cisplatin (Cis) (TCPMVCis) is reported. TCPMVCis exhibited a cytotoxic IC50 of TCPMVCis on both A549 and MDA-MB-231 cell lines of 1.8 µM and 3.9 µM, respectively after 72 hours of incubation. The TCPMVFePt were prepared as potential MRI contrast agents. CONCLUSION: Cisplatin loaded VLP (TCPMVCis) is shown to enhance cisplatin cytotoxicity in cancer cell lines with its potency increased by 2.3-folds.

Innovative Applications of Plant Viruses in Drug Targeting and Molecular Imaging- A Review.

BACKGROUND: Nature had already engineered various types of nanoparticles (NPs), especially viruses, which can deliver their cargo to the host/targeted cells. The ability to selectively target specific cells offers a significant advantage over the conventional approach. Numerous organic NPs, including native protein cages, virus-like particles, polymeric saccharides, and liposomes, have been used for the preparation of nanoparticles. Such nanomaterials have demonstrated better performance as well as improved biocompatibility, devoid of side effects, and stable without any deterioration. OBJECTIVE: This review discusses current clinical and scientific research on naturally occurring nanomaterials. It also illustrates and updates the tailor-made approaches for selective delivery and targeted medications that require a high-affinity interconnection to the targeted cells. METHODS: A comprehensive search was performed using keywords for viral nanoparticles, viral particles for drug delivery, viral nanoparticles for molecular imaging, theranostics applications of viral nanoparticles and plant viruses in nanomedicine. We searched on Google Scholar, PubMed, Springer, Medline, and Elsevier from 2000 till date and by the bibliographic review of all identified articles. RESULTS: The findings demonstrated that structures dependent on nanomaterials might have potential applications in diagnostics, cell marking, comparing agents (computed tomography and magnetic resonance imaging), and antimicrobial drugs, as well as drug delivery structures. However, measures should be taken in order to prevent or mitigate, in pharmaceutical or medical applications, the toxic impact or incompatibility of nanoparticle-based structures with biological systems. CONCLUSION: The review provided an overview of the latest advances in nanotechnology, outlining the difficulties and the advantages of in vivo and in vitro structures that are focused on a specific subset of the natural nanomaterials.

Coronaviruses in children: A review of potential mechanisms of childhood protection.

AIM: The 2019 coronavirus disease (COVID-19) has spread worldwide and the number of cases continues to rise exponentially. Epidemiologic reports indicate that severity of illness increases with age. However, the reasons behind the relative protection of children and infants are unclear. Whether the rationale is host-related or virus dependent is important to determine since the latter could change with viral mutations. We review factors that could affect the susceptibility of children to the novel coronavirus. METHODS: We search publications indexed on PUBMED. RESULTS: Descriptions of the pathophysiology of current and previous coronavirus infections suggest several viral targets and immunomodulatory pathways affecting the severity of illness. There is limited evidence to suggest age-variability of viral cell receptors and transmembrane co-factors required for coronavirus entry and replication. However, the ensuing cytokine storm and the effect of higher melatonin in children are age-dependent and could explain decreased disease variability in children. CONCLUSION: We believe that current evidence suggests host factors can play a role in disease severity in children and thus may remain protective despite potential virus mutation in the future. However, we recognise and discuss avenues of future research that can further illuminate the reasons children are protected from severe COVID-19 illness.

Heat shock proteins gene expression and physiological responses in durum wheat (Triticum durum) under salt stress.

Salt stress is a major abiotic stress causing adverse effects on plant growth and development. The aim of this study was to investigate the effect of NaCl stress on growth, stress indicator parameters (lipid peroxidation, chlorophyll content and proline content), yield, and the expression of heat shock proteins genes (Hsp17.8, Hsp26.3, Hsp70 and Hsp101) of five Jordanian durum wheat (Triticum durum) landraces. Plants were irrigated with tap water as control or 200 mM NaCl. Significant differences among the 5 Triticum durum landraces in terms of growth parameters, stress indicator parameters, and expression of heat shock proteins genes were observed. Salt stressed landraces demonstrated decreased growth, increased levels of stress indicator parameters, and upregulation in Hsp17.8, Hsp26.3, Hsp70 and Hsp101 expression. Landraces T11 and M23 showed the highest growth, lowest levels of stress indicator parameters, and high expression of heat shock protein genes under NaCl stress. Whereas, J2 and A8 landraces showed the lowest growth, highest levels of stress indicator parameters and low expression of heat shock protein genes under NaCl stress. In conclusion, NaCl stress caused significant reduction in growth parameters, increased level of lipid peroxidation and proline content and upregulation in heat shock proteins gene expression levels. Growth, stress indicator parameters and gene expression results suggest that T11 and M23 landraces are the most NaCl stress tolerant landraces and could be used to enhance the gene pool in wheat breeding programs.

SARS-CoV-2 and Coronavirus Disease 2019: What We Know So Far.

In December 2019, a cluster of fatal pneumonia cases presented in Wuhan, China. They were caused by a previously unknown coronavirus. All patients had been associated with the Wuhan Wholefood market, where seafood and live animals are sold. The virus spread rapidly and public health authorities in China initiated a containment effort. However, by that time, travelers had carried the virus to many countries, sparking memories of the previous coronavirus epidemics, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and causing widespread media attention and panic. Based on clinical criteria and available serological and molecular information, the new disease was called coronavirus disease of 2019 (COVID-19), and the novel coronavirus was called SARS Coronavirus-2 (SARS-CoV-2), emphasizing its close relationship to the 2002 SARS virus (SARS-CoV). The scientific community raced to uncover the origin of the virus, understand the pathogenesis of the disease, develop treatment options, define the risk factors, and work on vaccine development. Here we present a summary of current knowledge regarding the novel coronavirus and the disease it causes.

Albumin Nano-Encapsulation of Piceatannol Enhances Its Anticancer Potential in Colon Cancer Via Downregulation of Nuclear p65 and HIF-1α.

Piceatannol (PIC) is known to have anticancer activity, which has been attributed to its ability to block the proliferation of cancer cells via suppression of the NF-kB signaling pathway. However, its effect on hypoxia-inducible factor (HIF) is not well known in cancer. In this study, PIC was loaded into bovine serum albumin (BSA) by desolvation method as PIC-BSA nanoparticles (NPs). These PIC-BSA nanoparticles were assessed for in vitro cytotoxicity, migration, invasion, and colony formation studies and levels of p65 and HIF-1α. Our results indicate that PIC-BSA NPs were more effective in downregulating the expression of nuclear p65 and HIF-1α in colon cancer cells as compared to free PIC. We also observed a significant reduction in inflammation induced by chemical colitis in mice by PIC-BSA NPs. Furthermore, a significant reduction in tumor size and number of colon tumors was also observed in the murine model of colitis-associated colorectal cancer, when treated with PIC-BSA NPs as compared to free PIC. The overall results indicate that PIC, when formulated as PIC-BSA NPs, enhances its therpautice potential. Our work could prompt further research in using natural anticancer agents as nanoparticels with possiable human clinical trails. This could lead to the development of a new line of safe and effective therapeutics for cancer patients.

4,977-bp human mitochondrial DNA deletion is associated with asthenozoospermic infertility in Jordan.

Male infertility is commonly associated with sperm abnormalities including asthenozoospermia. The molecular basis of asthenozoospermia was linked to mitochondrial DNA (mtDNA) mutations. The 4,977-bp human mtDNA deletion is one of the most common mutations of spermatozoa and results in loss of about 33% of the mitochondrial genome. In this preliminary study, we aimed to investigate the presence of 4,977-bp mtDNA deletion in asthenozoospermic infertile men in Jordan. Semen specimens of 120 asthenozoospermic infertile men and 80 normozoospermic individuals were collected at the in vitro fertilization unit. MtDNA was extracted after the enrichment of spermatozoa; then, polymerase chain reaction was performed using 4,977-bp mtDNA deletion-specific primers. The deletion of 4,977-bp mtDNA was detected in 79.2% of asthenozoospermic patients compared to 10% in normozoospermic controls. The results showed a significant association between the presence of 4,977-bp mtDNA deletion and the asthenozoospermia and infertility (OR = 34.2000, 95% CI = 14.57-80.26, p-value < .001). In conclusion, our findings underscored a strong association between 4,977-bp mtDNA deletion and asthenozoospermia in the Jordanian population.

X-ray repair cross-complementing protein 1 and 3 polymorphisms and susceptibility of breast cancer in a Jordanian population.

OBJECTIVES: To elucidate the contribution of x-ray repair cross-complementing (XRCC) protein 1 399Gln, XRCC3 241M, and XRCC3-5'-UTR polymorphisms to the susceptibility of breast cancer (BC) in a Jordanian population. METHODS: Forty-six formalin fixed paraffin embedded tissue samples from BC diagnosed female patients, and 31 samples from the control group were subjected to DNA sequencing. Samples were collected between September 2013 and December 2014. RESULTS: The XRCC1 Arg399Gln genotype did not exhibit any significant correlation with the susceptibility of BC (odds ratio [OR]=1.45, 95% confidence interval [CI]: 0.60-3.51) (p=0.47). Likewise, XRCC3 M241T genotype did not show significant correlation with BC (OR=2.02, 95% CI: 0.50-8.21) (p=0.40). However, distribution of XRCC3-5'UTR (rs1799794 A/G) genotype showed a significant difference between the patient and control group (OR=0.73, 95% CI: 0.06-8.46) (p=0.02). CONCLUSION: The XRCC3-5'UTR (rs1799794) G allele frequency was higher in cancer patients while XRCC1 (rs25487) and XRCC3 (rs861539) did not show any significant correlation with susceptibility of BC in the selected Jordanian population. Contribution of other environmental factors should be studied in future works, as well as the response of cancer therapy.