Aldehyde dehydrogenases (ALDH) expression in cancer tissues as potential pharmacological targets for therapeutic intervention. Probing ALDH expression and function in 2D- and 3D-cultured cancer cell lines

The aldehyde dehydrogenase (ALDH) superfamily is gaining momentum in regard to stem cell and cancer research. However, their regulation and expression in the cancer microenvironment is poorly understood. The aim of this work was to understand the role of selected ALDH isoforms (1A1, 1A2, 1A3, 1B1, 2, 3A1 and 7A1) in colorectal cancer (CRC) and explore the impact of hypoxia on their expression. CRC cell lines (HT29, DLD-1, SW480 and HCT116) were grown under normoxic or hypoxic conditions (0.1% O2) and HT29 and DLD-1 in spinner flasks to generate multicellular spheroids (MCS). Hypoxia was demonstrated to have an impact on the ALDH expression, which appeared cell-specific. Notably, ALDH7A1 was induced upon exposure to hypoxia in both HT29 and DLD-1 cells, shown to be expressed in the hypoxic region of the MCS variants and in 5/5 CRC xenografts (HT29, DLD-1, HCT116, SW620, and COLO205). ALDH7A1 siRNA knockdown studies in DLD-1 cells resulted in significant reduction of viable cells and significant increase in ROS levels, suggesting ALDH7A1 to possess antioxidant properties. These findings were further supported using isogenic H1299/RFP and H1299/ALDH7A1 lung cancer cell lines. ALDH7A1, however, was found not to be involved in inhibiting the pharmacological effect or causing resistance to different cytotoxic and molecularly targeted anticancer drugs. To unravel the functional role of ALDH7A1, 9 compounds obtained from a virtual screening of 24,000 compounds from the Maybridge collection of compounds were used to probe ALDH7A1 functional activity. One compound, HAN00316, was found to inhibit the antioxidant properties of ALDH7A1 and thus could be a good starting point for further chemical tool development. Although this study underpins a potential important role of ALDH7A1 in hypoxic CRC, further work is required to fully validate its potential as a biomarker and/or pharmacological target.Jordan University of Science and Technolog

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

Knowledge, awareness and practices regarding dietary supplements in Jordan

Purpose: To investigative the knowledge, attitudes and beliefs pertaining to dietary supplements (DS) use in Jordan. Methods: Participants were enrolled from four main cities in Jordan, viz, Amman, Zarqa, Irbid, and Mafraq, to fill a self-administered questionnaire which explored the objectives of the study. Results: Most participants (80 %) knew what DS are. The prevalence of DS use was high (62.1 %) and significantly higher among females (p = 0.004). The most commonly consumed DS among users were in the form of multivitamins (93.0 %), vitamin D (65.8 %) and vitamin C (57.6 %). About half of the participants (46.2 %) believed that DS have no side effects. The most frequent source of information for participants about DS was from non-reliable references, such as social media. Self-prescription was the most common approach by DS users for supplement intake. Finally, the common hypothesis of associating healthy habits with DS use was not found to be true among Jordanians. Conclusion: These results highlight the need to implement appropriate awareness programs for the public regarding DS benefits and hazards, and especially to advise the public not to initiate DS use without first consulting an appropriate healthcare professional

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

BackgroundThe 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.MethodsConsecutive 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.ResultsGLS1 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.ConclusionThe increased expression of GLS1 and GLS2 may be explored as a new treatment for head and neck cancers

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

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

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

Medical students’ relative immunity, or lack thereof, against COVID-19 emotional distress and psychological challenges; a descriptive study from Jordan [version 2; peer review: 2 approved, 1 approved with reservations]

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

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-β1, 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

Re-engineering of the Duocarmycin Structural Architecture Enables Bioprecursor Development Targeting CYP1A1 and CYP2W1 for Biological Activity

A library of duocarmycin bioprecursors based on the CPI and CBI scaffolds was synthesized and used to probe selective activation by cells expressing CYP1A1 and 2W1, CYPs known to be expressed in high frequency in some tumors. Several CPI-based compounds were pM–nM potent in CYP1A1 expressing cells. CYP2W1 was also shown to sensitize proliferating cells to several compounds, demonstrating its potential as a target for tumor selective activation of duocarmycin bioprecursors