Investigating Carvedilol's Repurposing for the Treatment of Non-Small Cell Lung Cancer via Aldehyde Dehydrogenase Activity Modulation in the Presence of ß-Adrenergic Agonists.

Repurposing existing drugs appears to be a potential solution for addressing the challenges in the treatment of non-small cell lung cancer (NSCLC). ß-adrenoceptor antagonist drugs (ß-blockers) have tumor-inhibiting effects, making them promising candidates for potential NSCLC treatment. This study investigates the anticancer potential of a subset of ß-blockers in NSCLC cell lines; A549 and H1299. Additionally, it investigates the underlying mechanism behind ß-blockers' anticancer effect by influencing a potential novel target named aldehyde dehydrogenase (ALDH). The MTT assay assessed ß-blockers' cytotoxicity on both cell lines, while Western blot and NADH fluorescence assays evaluated their influence on ALDH protein expression and activity. Carvedilol (CAR) was the most effective blocker in reducing cell survival of A549 and H1299 with IC50 of 18 µM and 13.7 µM, respectively. Significantly, CAR led to a 50% reduction in ALDH expression and 80% decrease in ALDH activity in A549 cells, especially when combined with ß-agonists, in comparison to the control. This effect might be attributed to ß-agonist blockade or an alternative pathway. This novel finding adds to our understanding of CAR's multifaceted anticancer properties, implying that combining CAR with ß-agonists could be a useful strategy for lung cancer treatment.

Depression Among University Students in Jordan After the COVID-19 Pandemic: A Cross-Sectional Study.

Background: University students encounter stressors that make them more susceptible to depression than the general population. Depression negatively impacts mental and physical health. Our study assessed the prevalence of depression among university students in Jordan and its associated predictors after the COVID-19 pandemic. Methods: We conducted this cross-sectional online survey study in the first quarter of 2022 by sending an online questionnaire to university students aged 18 years and older. This study assessed the symptoms of depression using the Patient Health Questionnaire-9 (PHQ-9). Binary logistic regression analysis was used to identify associated predictors of depression. Results: A total of 535 university students participated in this study. The mean depression score for the study participants was 13.9 (SD: 7.1) out of 27, representing a moderate level of depression. Among the participants, 26.2% had moderate, 19.3% had moderately severe, and 25.8% had severe depression. Students who drink three or more cups of coffee per day, have had an evaluation of their psychological state by specialists before, and have been diagnosed with any mental illness were more likely to have a higher depression score compared to others (p<0.05). On the other hand, students who were aged 24 years and older and those who practiced regular exercise were less likely to have a higher depression score compared to others (p<0.05). Conclusion: We found a high prevalence of depression among university students in Jordan. This result is vital for decision-makers to implement a plan to prevent and manage this mental health issue.

Medical, Dental, and Nursing Students' Experience with Virtual Practical Sessions: A Cross-Sectional Study in a Developing Country.

Background: The COVID-19 pandemic has disrupted the scope of healthcare education and shifted the teaching methods from on-campus to virtual. The impact of such a shift has rarely been investigated, and limited evidence exists about students' experience in terms of effort made and time spent, especially for laboratory sessions. Assessing students' experiences will provide paramount evidence to fine-tune laboratory virtual learning sessions. Objective: To assess students' experience of virtual (online) laboratory sessions versus on-campus laboratory sessions, including preference, time spent, the effort made, ability to remember instructions, and preference for future teaching. Methods: A cross-sectional study was utilized. A Google Forms questionnaire was prepared and sent to medicine, dentistry, and nursing school students registered at Jordan University of Science and Technology (JUST) during the 2019/2020 academic year. Self-reported preference, time spent, efforts made, ability to remember instructions and preference for future teaching were assessed for virtual versus on-campus anatomy, pathology, microbiology, histology, and physiology laboratory sessions. Results: A total of 455 students participated in this questionnaire. More students in histology (55.2%), pathology (57.4%), and microbiology (55.3%) laboratories, but not anatomy (39.6%) physiology (443.95), reported preferring virtual sessions over on-campus sessions. More students from histology (35.6%) and microbiology (37.0%) reported spending less effort than on-campus sessions. More than half of the participants agreed that virtual laboratory sessions consumed less time than on-campus sessions. Participants reported that they cannot remember the instruction given during virtual teaching compared to on-campus teaching. Differences in students' experiences were detected by gender, major, and year of study. Conclusion: The COVID-19 pandemic has the potential to change the future of healthcare education, and preparation for future crises is paramount. Effort made, time spent, ability to remember, and preference for virtual education should be considered in terms of gender, major of study, and year. These differences should also be reflected in the planning of virtual sessions for effective implementation.

Effect of 2% Topical Lidocaine Gel on Discomfort from Electrical Stimulation During Nerve Conduction Studies- A Prospective Double-Blind Placebo-Controlled Study.

Purpose: Procedure discomfort can limit electrodiagnostic studies. Reducing discomfort can maximize the benefits of these diagnostic tools. This study targeted the discomfort associated with nerve conduction studies (NCS). Patients and Methods: This was a prospective randomized double-blind placebo-controlled study comparing the effect of topical lidocaine gel (2%) versus analgesic-free lubricant gel (K-Y gel) on pain perception during NCS. Sequential patients (n=130) referred for routine NCS participated in the study. We applied 1 mL of lidocaine gel to one palm, and 1 mL of K-Y gel to the other as a control. After 20-45 min of application, graded increments of electrical stimulation intensity were delivered to record the median and ulnar mixed palmar nerve responses. Patients were then asked to score the degree of pain felt from electrical stimulation over each palm using the Wong-Baker Faces Pain Scale (WBFPS) and the Numeric Rating Scale (NRS), independent of baseline pain. Results: Mean WBFPS and NRS scores for lidocaine-treated palms were significantly lower than those for controls using parametric paired t-test (3.79 vs 4.37 and 3.35 vs 3.78 respectively, all p-values<0.05). Subgroup analysis showed a significant decrease in mean scores in females, patients aged ≤50 years, patients without a history of previous NCS, and patients without comorbidities (all p-values<0.05). Median scores using nonparametric Wilcoxon ranked test also showed statistically significant differences (all p-values<0.05). Conclusion: The results indicate that topical lidocaine 2% gel reduces discomfort associated with NCS. However, despite the statistical significance, clear clinical significance may be lacking. Clinical implementation may be considered for the subgroups that showed the greatest benefit. Further studies that incorporate more efficient drug delivery methods may yield better results.

Serum Leptin Receptor and the rs1137101 Variant of the LEPR Gene Are Associated with Bladder Cancer.

Globally, bladder cancer (BC) is one of the ten most common tumors. Obesity is a worldwide problem associated with an increased BC risk. Considering that levels of leptin and/or its receptor are often deregulated in obese individuals, we hypothesized that they could contribute to BC. To test this hypothesis, we utilized a case-control study in which 116 patients with a confirmed diagnosis of BC and 116 controls were recruited. The serum levels of leptin and leptin receptor were measured. Patients and controls were also genotyped for SNPs in the LEP (rs7799039, rs791620, and rs2167270) and LEPR genes (rs1137100, rs1137101, and rs1805094). The univariate analysis indicated that BC patients had significantly higher levels of leptin and lower levels of leptin receptor (p < 0.05). Moreover, rs7799039 of LEP and rs1137101 of LEPR were associated with BC (p < 0.05). In the multivariate analysis, leptin receptor levels were protective (OR: 0.98, 95% CI = 0.97-0.99, p = 0.002) while the GG genotype of rs1137101 of LEPR increased BC risk (OR: 3.42, 95% CI = 1.27-9.20, p = 0.02). These findings highlight that lifestyle changes could be useful in preventing BC and that disturbances in energy metabolism could play a role in the pathobiology of BC.

Niosomal Delivery of Celecoxib and Metformin for Targeted Breast Cancer Treatment.

Breast cancer continues to be a prominent worldwide health concern and requires continued investigation into innovative therapeutic approaches. Here, we report the first investigation into the therapeutic efficacy of combining Metformin (MET) and Celecoxib (CXB), both in free and niosomal form, for the treatment of breast cancer. Our investigation encompassed the characterization of these niosomal drug carriers, their stability assessment, and their effect on breast cancer cell models. The thin-film hydration technique was employed to prepare niosomes with spherical, uniform-size distributions and high encapsulation efficiencies. The niosomes were characterized by TEM, particle size analyzer, and ATR-FTIR. The niosomes with an average size of 110.6 ± 0.6 and 96.7 ± 0.7, respectively, for MET and CXB were stable when stored at 4 °C for three months with minimal drug leakage, minor changes in encapsulation efficiency and size, and unchanged physicochemical parameters. Evaluation in two-dimensional (2D) and three-dimensional (3D) viability assays demonstrated an increased cytotoxicity of encapsulated drugs when compared to their free-drug counterparts. Additionally, the combination of Metformin Niosomal Particles (MET NPs) and Celecoxib Niosomal Particles (CXB NPs) led to decreased cell viability in both 2D and 3D models compared to each drug administered individually. When comparing the effect of the niosomal versus the free combination of the drugs on cell migration, we found that both interventions effectively prevented cell migration. However, the efficacy of the niosomes' combination was not superior to that of the free drug combination (p < 0.05). In conclusion, the results of this study provide valuable insights into the potential application of combining MET and CXB nanoparticle delivery systems to breast cancer treatment. Exploring the in vivo application of this drug delivery system could open new avenues for more effective and targeted therapeutic approaches for breast cancer patients.

Discovery of a novel genetic variant in the N-acetyltransferase2 (NAT2) gene that is associated with bladder cancer risk.

Smoking is a main risk factor for bladder cancer (BC). NAT2 is a drug-metabolizing enzyme that catalyses the detoxification of many xenobiotics and carcinogens. Single nucleotide polymorphism (SNP) in NAT2 results in different acetylation phenotypes (fast, intermediate or slow). Certain NAT2 SNPs were associated with BC and/or modified the association of BC with smoking. However, limited evidence is available among BC patients or smokers from Jordan. This study aimed to discover novel SNPs in NAT2 and to assess the association with BC. This was a case-control study among 120 BC patients and 120 controls. Amplification of a 446 bp fragment of NAT2 encoding the N-catalytic domain was conducted using a polymerase chain reaction. Gene sequencing was done using Sanger-based technology. A total of 40 SNPs were detected. Two variants were significantly associated with BC (p<0.05); namely a novel c.87G>A and the reported c.341T>C. Regarding c.87G>A, genotype distribution was significantly associated with BC and subgroup analysis confirmed that this was significant in both smokers (p=0.007) and non-smokers (p=0.001). Regression subgroup analysis suggested GA as a risk factor among smokers (AOR= 2.356). The frequencies of TC and CC genotypes of c.341T>C were significantly higher in BC (p<0.05). This was statistically significant among smokers only (p=0.044), upon subgroup analysis. Multivariate analysis showed that subjects with TC genotype are 6.15 more likely to develop BC and regression subgroup analysis revealed TC as a risk factor among smokers (AOR=5.47). This is the first study from Jordan to report the association of smoking and two NAT2 variants with BC. The data supports the use of GA and TC genotypes of the novel c.87G>A and the reported c.341T>C SNPs, respectively as potential biomarkers of BC, particularly among smokers. Future investigations with a larger population are required to support our findings.

Royal jelly mediates fibrotic signaling, collagen cross-linking and cell proliferation in cardiac fibroblasts.

Royal jelly (RJ) is a multifunctional bee product with a unique composition and wide-ranging biological properties, including antioxidant, anti-inflammatory and antiproliferative activities. Still, little is known about the possible myocardial protective properties of RJ. Considering that sonication could enhance RJ bioactivity, this study aimed to assess the effects of non-sonicated (NS) and sonicated (S) RJ on fibrotic signaling, cell proliferation, and collagen production in cardiac fibroblasts. S-RJ was produced by ultrasonication at 20 kHz. Ventricular fibroblasts isolated from neonatal rats were cultured and treated with different concentrations of NS-RJ or S-RJ (0, 50, 100, 150, 200, and 250 µg/well). S-RJ significantly depressed the expression levels of transglutaminase 2 (TG2) mRNA across all the concentrations tested and was inversely associated with the expression of this profibrotic marker. S-RJ and NS-RJ displayed distinct dose-dependent effects on mRNA expression of several other profibrotic, proliferation, and apoptotic markers. Unlike NS-RJ, S-RJ elicited strong negative dose-dependent relationships with the expression of profibrotic markers (TG2, COL1A1, COL3A1, FN1, CTGF, MMP-2, α-SMA, TGF-ß1, CX43, periostin), as well as proliferation (CCND1) and apoptotic (BAX, BAX/BCL-2) markers, indicating that RJ dose-response effects were significantly modified by sonification. NS-RJ and S-RJ increased the content of soluble collagen, while decreasing collagen cross-linking. Collectively, these findings show that S-RJ has a greater range of action than NS-RJ for downregulating the expression of biomarkers associated with cardiac fibrosis. Reduced biomarker expression and collagen cross-linkages upon cardiac fibroblast treatment with specific concentrations of S-RJ or NS-RJ suggests putative roles and mechanisms by which RJ may confer some protection against cardiac fibrosis.

Genetic variation in the ADIPOQ gene and serum adiponectin increase the risk of bladder cancer.

Bladder cancer (BC) is the 10th most common cancer worldwide. Genetic studies estimated 30% heritability in BC risk. Adiponectin is an adipocytokine that has important roles in the regulation of energy metabolism. Recent evidence suggests dysregulation of adiponectin levels in BC tissues. Serum level of adiponectin is influenced by single nucleotide polymorphisms (SNPs) in the ADIPOQ gene. However, limited evidence is available regarding the association between adiponectin serum levels or SNPs in ADIPOQ and BC risk. This study aimed to assess whether adiponectin serum levels or SNPs in ADIPOQ may modify BC risk. In this case-control study, 114 BC patients were recruited along with 114 controls. Study subjects were genotyped for variations in ADIPOQ SNPs, namely rs17300539, rs266729, rs2241766, and rs1501299. Adiponectin levels were measured from the serum of study subjects. Our analysis showed that the G allele and the GG genotype of rs1501299 were significantly more frequent in BC patients compared to those in the control group (p-value < 0.05). Moreover, two ADIPOQ haplotypes containing the above G allele were associated with increased BC risk (p-value < 0.05). Multivariate analysis showed that increased serum adiponectin, smoking or age were all significant predictors of BC (p-value < 0.05). The data supports use of serum adiponectin and the G allele of rs1501299 SNP in ADIPOQ as potential biomarkers and/or targets in BC. To further validate findings in this study, larger populations of various ethnicities and/or genetic backgrounds are required. More investigations on the functional role of adiponectin in BC will also provide better understanding of potential targeting adiponectin for BC treatment.

Prevalence and predictive factors for infertility-related stress among infertile couples: A cross-sectional study from Jordan and the occupied Palestinian territories.

OBJECTIVES: To assess the level of infertility-related stress, associated socio-economic, and demographic factors among infertile couples living in Jordan and those living under the chronic Israeli-Palestinian conflict in the occupied Palestinian territories. METHODS: A cross-sectional study was carried out in a number of fertility and reproductive clinics in Jordan and occupied Palestinian territories over a period of 6 months. Trained clinical pharmacists interviewed the identified couples. RESULTS: A total of 443 participants were interviewed. Three variables were significantly and independently associated with global stress scores. The need of parenthood appears higher in women than men among infertile couples in Jordan and Palestine (p=0.005). The country of origin (p<0.001) made the greatest contribution of unique variance followed by family type (p=0.035). Additionally, a significant contribution to the model was carried out by the number of clinicians who followed up on the case (p=0.013). The average total cost of treatment since the problem had been diagnosed was 2936±4529 Jordanian dinar, which may be of concern to both Jordanians and Palestinians given the limited resources available in developing nations. CONCLUSION: This study shows a significant degree of stress among infertile couples. The place of origin, family structure, and presence of medical insurance had a significant impact on the infertility global stress score. This study emphasizes the necessity for specific psychological therapies that are currently lacking in public healthcare practices in both Jordan and Palestine.

Normalization of Vitamin D Serum Levels in Patients with Type Two Diabetes Mellitus Reduces Levels of Branched Chain Amino Acids.

Background and Objectives: Vitamin D is involved in pancreatic beta-cell function, insulin sensitivity, and inflammation. Further, elevation in branched-chain amino acids (BCAAs) has been implicated in type 2 diabetes (T2DM) pathology. However, the relationship between vitamin D and BCAAs in T2DM remains unclear. The current study aimed to investigate the relationship between vitamin D and BCAAs in T2DM. Materials and Methods: In total, 230 participants (137 with T2DM and 93 healthy controls) were recruited in a cross-sectional study. Furthermore, an additional follow-up study was performed, including 20 T2DM patients with vitamin D deficiency. These patients were prescribed weekly vitamin D tablets (50,000 IU) for three months. The levels of several biochemical parameters were examined at the end of the vitamin D supplementation. Results: The results showed that patients with T2DM had higher serum levels of BCAAs and lower serum levels of 25-hydroxyvitamin D (25(OH)D) compared with those of the healthy controls (p < 0.01). The serum levels of vitamin D were negatively correlated with BCAA levels in T2DM patients (r = −0.1731, p < 0.05). In the follow-up study, 25(OH)D levels were significantly improved (p < 0.001) following vitamin D supplementation. Vitamin D supplementation significantly reduced the levels of BCAAs, HbA1c, total cholesterol, triglycerides, and fasting glucose (p < 0.01). Conclusion: Overall, these results suggest a role for BCAAs and vitamin D in the etiology and progression of T2DM. Thus, managing vitamin D deficiency in patients with T2DM may improve glycemic control and lower BCAA levels.

Prevalence and Predictive Factors of Masked Depression and Anxiety among Jordanian and Palestinian Couples: A Cross-Sectional Study.

Although anxiety and depression are among the most prevalent mental disorders worldwide, they continue to gain less attention than their physical counterparts in terms of health care provision and population mentalisation. This cross-sectional study explores and compares the national prevalence of depression and anxiety signs/symptoms and well as identifying associated socio-demographic factors among Jordanian and Palestinian fertile couples. Four-hundred and sixty-nine participants were eligible for inclusion and agreed to participate in the study. The mean score for HAM-A and BDI-II were 12.3 ± 8.2 and 15.30 ± 10.0, respectively. According to the grading of HAM-A and BDI-II, the majority of the participants have graded themselves to be mildly anxious (N = 323, 68.9%) and around one third of participants (N = 148, 31.6%) moderately to severe depressed. The suicidal intent was remarkable and of concern where around 18.6% of participants had suicidal thoughts and wishes. There was a significant correlation between both HAM-score and BDI-II score and age [p = 0.01, p = 0.011, respectively], body weight [p = 0.01, p = 0.006, respectively], and total monthly income [p < 0.001, p < 0.001, respectively]. Our findings ought to alert healthcare professionals and other interested parties that there is a high burden of anxiety and depression symptoms among Jordanian and Palestinian couples. To support Jordanian and Palestinian couples' mental health, healthcare professionals, researchers, and educators favoured to concentrate on creating efficient and culturally relevant education, preventive, and intervention procedures utilising evidence-based guidelines.

Osteoporosis among Postmenopausal Women in Jordan: A National Cross-Sectional Study.

Osteoporosis is considered a widespread health problem that affects senior citizens, particularly older women, after the menopause. This national study aimed to estimate the prevalence of osteoporosis among Jordanian postmenopausal women and to determine the association of demographic and nutritional factors, such as calcium and vitamin D supplement intake, with osteoporosis in postmenopausal women. A cross-sectional study was conducted among 884 postmenopausal women aged ≥50 years. A multistage sampling technique was used to select participants from three geographic regions of Jordan (north, middle, and south). The data were collected from the participants by a team of field researchers comprising men and women through a standard questionnaire. The prevalence of osteoporosis was 19.8% among postmenopausal Jordanian women. The study results showed that age (p ˂ 0.001), geographic region (p = 0.019), occupation (p = 0.002), and educational level (p = 0.001) were significantly associated with osteoporosis. Moreover, osteoporosis was significantly associated with calcium and vitamin D supplement intake (p < 0.05). There is a high prevalence of osteoporosis among postmenopausal Jordanian women. Therefore, there is a need to educate women at this age, and probably at an earlier age, to prevent or reduce the development of osteoporosis.

In vitro radiosensitization of breast cancer with hypoxia-activated prodrugs.

KP167 is a novel hypoxia-activated prodrug (HAP), targeting cancer cells via DNA intercalating and alkylating properties. The single agent and radiosensitizing efficacy of KP167 and its parental comparator, AQ4N, were evaluated in 2D and 3D cultures of luminal and triple negative breast cancer (TNBC) cell lines and compared against DNA damage repair inhibitors. 2D normoxic treatment with the DNA repair inhibitors, Olaparib or KU-55933 caused, as expected, substantial radiosensitization (sensitiser enhancement ratio, SER0.01 of 1.60-3.42). KP167 induced greater radiosensitization in TNBC (SER0.01 2.53 in MDAMB-231, 2.28 in MDAMB-468, 4.55 in MDAMB-436) and luminal spheroids (SER0.01 1.46 in MCF-7 and 1.76 in T47D cells) compared with AQ4N. Significant radiosensitization was also obtained using KP167 and AQ4N in 2D normoxia. Although hypoxia induced radioresistance, radiosensitization by KP167 was still greater under 2D hypoxia, yielding SER0.01 of 1.56-2.37 compared with AQ4N SER0.01 of 1.13-1.94. Such data show KP167 as a promising single agent and potent radiosensitiser of both normoxic and hypoxic breast cancer cells, with greater efficacy in TNBCs.

WLBU2 Antimicrobial Peptide as a Potential Therapeutic for Treatment of Resistant Bacterial

Antimicrobial resistance is considered a major health problem, worldwide. It is significantly associated with high morbidity and mortality rates. The current antibiotics have limited therapeutic efficacy in providing treatment for multidrug resistant bacteria. Accordingly, research in the antimicrobial field has been directed toward the discovery of new agents to overcome bacterial resistance. Antimicrobial peptides (AMP) have been extensively studied as potential antimicrobial agents with lower incidence of drug resistance compared to conventional antibiotics. WLBU2 is an engineered cationic AMP with promising antibacterial activity. It is composed of 24 amino acids including; 13 arginine, 8 valine and 3 tryptophan residues. Findings from in vitro and in vivo studies showed that WLBU2 is a potent peptide with a broad spectrum activity against Gram-positive, Gram-negative, multidrug resistant, and biofilm forming bacteria. Additionally, WLBU2 appears as a salt-resistant peptide with potential application for treatment of infections at conditions with disturbed normal salt homeostasis. Furthermore, WLBU2 was found as AMP with limited host toxicity. Recent investigations have shown that combination of WLBU2 with conventional antibiotics can result in synergism against resistant bacteria. In this review we highlight the evidence supporting the promising properties of WLBU2 as an antibacterial agent with potential applications for the treatment of infections caused by resistant bacteria.

Clinical and biological indicators of periodontal disease in obese and non-obese adults with and without bronchial asthma.

OBJECTIVE: The present study aims to assess clinical and inflammatory parameters as indicators for periodontal disease in obese and non-obese adults with and without bronchial asthma (BA). METHODS: 168 patients visiting the outpatient pulmonary clinics were divided into four groups according to BA and obesity. Obesity was defined by body mass index (BMI) and BA was diagnosed by a pulmonary consultant and being on inhaled asthma medication for at least 12 months. Participants were examined for clinical periodontal parameters and samples of gingival crevicular fluid (GCF) were taken and analyzed for the levels of 5 different inflammatory cytokines. RESULTS: Compared with controls, obese asthmatic group had significant higher mean clinical attachment loss (CAL) (2.64 vs. 1.00, p < .001). Also, the occurrence of periodontitis was significantly higher among obese patients compared to non-obese patients (p = 0.003). Multivariate logistic regression model showed that age was the strongest predictor of periodontitis (aOR = 1.23). The levels of IL-1ß and IL-8 were significantly higher in the non-obese asthmatic group compared to the control group (p < 0.05). The level of IL-6 was significantly lower in the control group compared to the other groups (p < 0.001). Obese patients had significantly higher concentration of hsCRP compared to non-obese patients (p < 0.001). There was no significant difference in the level of TNF- α between groups. CONCLUSIONS: BA and obesity combined did not seem to be associated with a significant increased risk of having periodontitis. BA and obesity are associated with increased levels of some local proinflammatory cytokines which adds to the local and systemic inflammatory burden.

The Expression of Glutaminases and their Association with Clinicopathological Parameters in the Head and Neck Cancers.

BACKGROUND: The increased glutamine metabolism is a characteristic feature of cancer cells. The interconversion between glutamine and glutamate is catalyzed by two glutaminase isoforms, GLS1 and GLS2, which appear to have different roles in different types of cancer. We investigated for the first time the protein expression of GLS1 and GLS2, and their correlation with advanced clinicopathological parameters in head and neck cancers. METHODS: Consecutive slides from a tissue microarray comprised of 80 samples ranging from normal to metastatic were stained immunohistochemically for GLS1, GLS2, HIF-1α or CD147. Following analysis by two expert pathologists, we carried out a statistical analysis of the scores. RESULTS: GLS1 and GLS2 were found to be upregulated at the protein level in head and neck tumours compared to normal tissues, and this increased expression correlated positively (GLS1) and negatively (GLS2) with tumor grade, indicating a shift of expression between GLS enzyme isoforms based on tumor differentiation. Increased expression of GLS1 was associated with high CD147 expression, and elevated GLS2 expression was associated with both high CD147 and high HIF-1α expressions. The correlation of the GLS1 and GLS2 with HIF-1α or CD147 was strongly associated with more advanced clinicopathological parameters. CONCLUSION: The increased expression of GLS1 and GLS2 may be explored as a new treatment for head and neck cancers.

Synergism between WLBU2 peptide and antibiotics against methicillin-resistant Staphylococcus aureus and extended-spectrum beta-lactamase-producing Enterobacter cloacae.

Infections caused by Methicillin-Resistant Staphylococcus aureus (MRSA) and Extended-Spectrum Beta-Lactamase (ESBL) producing Enterobacter cloacae are considered as major therapeutic challenge due to their multidrug-resistant (MDR) phenotype against conventional antibiotics. WLBU2 is an engineered cationic peptide with potent antimicrobial activity. This in-vitro study aimed to evaluate the effects of WLBU2 against clinical isolates of the aforementioned bacteria and assess whether synergistic effects can be achieved upon combination with conventional antibiotics. The minimum inhibitory concentrations (MICs) of antimicrobial agents against bacterial clinical isolates (n = 30/strain) were determined using the microbroth dilution assay. The minimum bactericidal concentrations (MBCs) of WLBU2 were determined from microbroth dilution (MICs) tests by subculturing to agar plates. MICs of WLBU2 were evaluated in the presence of physiological concentrations of salts including NaCl, CaCl2 and MgCl2. To identify bacterial resistance profile, MRSA were treated with Oxacillin, Erythromycin and Vancomycin, while Ceftazidime, Ceftriaxone, Ciprofloxacin and Imipenem were used against Enterobacter cloacae. Combination treatments of antibiotics and sub-inhibitory concentrations of WLBU2 were conducted when MICs indicated intermediate/resistant susceptibility. The MICs/MBCs of WLBU2 were identical for each respective bacteria with values of 0.78-6.25 µM and 1.5-12.5 µM against MRSA and Enterobacter cloacae, respectively. WLBU2 was found as salt resistant. Combination treatment showed that synergistic and additive effects were achieved in many isolates of MRSA and Enterobacter cloacae. Our data revealed that WLBU2 is a potent peptide with bactericidal activity. In addition, it demonstrated the selective advantage of WLBU2 as a potential therapeutic agent under physiological solutions. Our findings also support the combination of WLBU2 and conventional antibiotics with potential application for treatment of resistant bacteria.

Medical students' relative immunity, or lack thereof, against COVID-19 emotional distress and psychological challenges; a descriptive study from Jordan.

Background: Emotional distress is a major impact of COVID-19 among not only the general public but also healthcare workers including medical students. This study aimed at describing self-reported changes in emotional reactions associated with COVID-19 among medical students in Jordan and to assessing the potential effect of social media utilization on emotional distress among this group. Methods: A cross-sectional design was utilized to collect data early on during the outbreak in Jordan. All medical students in Jordan were eligible to complete an online questionnaire assessing self-reported emotional reactions to COVID-19 that covered four main domains: negative emotion (anxiety, worry, depression, panic, loneliness, and nervousness), positive emotion (happiness, joy, and excitement), sleep disorders (insomnia, shallow sleep, nightmares, and insufficient sleep), and aggression (verbal argument and physical fighting). The frequency of social media utilization as a main source of COVID-19 information was also assessed. Results: 59.9% of participants were females, 64.9% were enrolled at the two major medical schools in Jordan, and 59.6% were in the pre-clinical stage (years). A significant proportion of participants self-reported increased negative emotional levels of anxiety (49.2%), worry (72.4%), depression (23.1%), panic (22.6%), and nervousness (38.2%) and decreased positive emotional levels of happiness (44.8%), joy (47.3%), and feelings of excitement (45.1%). Self-reported sleep disorders were not as common (less than 15% for any of the four items), while arguing with others was at 26.7%. Significant differences by gender and academic year were detected. Almost half of participants reported using social media as a main source of COVID-19 information "most/all-the-times" with a significant effect of such on reducing emotional distress. Conclusion: The results suggest a potential effect of COVID-19 on the emotional distress of medical students. Addressing and mitigating such effects is crucial. The potential buffering effect of social media should be further investigated.

Leptin and the GA genotype of rs2167270 of the LEP gene increase the risk of prediabetes.

Prediabetes is a precursor stage that frequently develops to definitive type 2 diabetes mellitus (T2DM). Therefore, identifying individuals with prediabetes can allow for early intervention measures that delay or prevent disease progression to T2DM. Several biochemical changes appear to be associated with prediabetes, including an increase in the serum levels of leptin. In Jordan, this association has not been previously investigated. In the present study, the serum levels of leptin were measured in 122 prediabetes subjects and 122 controls. Furthermore, the genotypes of three single nucleotide polymorphisms in the LEP gene (rs7799039, rs2167270 and rs791620) were investigated for their association with prediabetes using PCR-restriction fragment length polymorphism. The results revealed a significant increase in serum leptin levels in the prediabetes group. It was also shown that the GA genotype and the A allele of rs2167270 were significantly associated with an increased risk of prediabetes (P<0.05). These findings were shown to be independent of body mass index, waist circumference and serum glucose levels. To the best of our knowledge, the present study is the first in Jordan to have reported an association between serum leptin levels and the GA genotype of rs2167270 with an increased risk of prediabetes, identified both in the univariate and multivariate models.