Overcoming Chemoresistance in Cancer: The Promise of Crizotinib.

Chemoresistance is a major obstacle in cancer treatment, often leading to disease progression and poor outcomes. It arises through various mechanisms such as genetic mutations, drug efflux pumps, enhanced DNA repair, and changes in the tumor microenvironment. These processes allow cancer cells to survive despite chemotherapy, underscoring the need for new strategies to overcome resistance and improve treatment efficacy. Crizotinib, a first-generation multi-target kinase inhibitor, is approved by the FDA for the treatment of ALK-positive or ROS1-positive non-small cell lung cancer (NSCLC), refractory inflammatory (ALK)-positive myofibroblastic tumors (IMTs) and relapsed/refractory ALK-positive anaplastic large cell lymphoma (ALCL). Crizotinib exists in two enantiomeric forms: (R)-crizotinib and its mirror image, (S)-crizotinib. It is assumed that the R-isomer is responsible for the carrying out various processes reviewed here The S-isomer, on the other hand, shows a strong inhibition of MTH1, an enzyme important for DNA repair mechanisms. Studies have shown that crizotinib is an effective multi-kinase inhibitor targeting various kinases such as c-Met, native/T315I Bcr/Abl, and JAK2. Its mechanism of action involves the competitive inhibition of ATP binding and allosteric inhibition, particularly at Bcr/Abl. Crizotinib showed synergistic effects when combined with the poly ADP ribose polymerase inhibitor (PARP), especially in ovarian cancer harboring BRCA gene mutations. In addition, crizotinib targets a critical vulnerability in many p53-mutated cancers. Unlike its wild-type counterpart, the p53 mutant promotes cancer cell survival. Crizotinib can cause the degradation of the p53 mutant, sensitizing these cancer cells to DNA-damaging substances and triggering apoptosis. Interestingly, other reports demonstrated that crizotinib exhibits anti-bacterial activity, targeting Gram-positive bacteria. Also, it is active against drug-resistant strains. In summary, crizotinib exerts anti-tumor effects through several mechanisms, including the inhibition of kinases and the restoration of drug sensitivity. The potential of crizotinib in combination therapies is emphasized, particularly in cancers with a high prevalence of the p53 mutant, such as triple-negative breast cancer (TNBC) and high-grade serous ovarian cancer (HGSOC).

Trying to Understand the Complicated Taxonomy in Amaranthus (Amaranthaceae): Insights on Seeds Micromorphology.

Amaranthus is a genus taxonomically complex because of its high morphological variability, which led to nomenclatural disorders, misapplication of names, and misidentifications. Floristic and taxonomic studies on this genus are still incomplete, and many questions remain open. Seed micromorphology has been shown to play an important role in the taxonomy of plants. Regarding Amaranthaceae and Amaranthus, investigations are rare, and they refer to one or a few species. With the primary aim to test if seed features are helpful in the taxonomy of Amaranthus, we here present a detailed SEM study on seed micromorphology in 25 Amaranthus taxa using morphometric methods. Seeds were collected from field surveys and herbarium specimens; 14 seed coat features (7 qualitative and 7 quantitative) were measured on 111 samples (up to 5 seeds per sample). The results obtained revealed that seeds micromorphology provides interesting new taxonomic data concerning some taxa (species and below ranks). In fact, we were able to distinguish a few seed types, including one or more taxa, i.e., blitum-type, crassipes-type, deflexus-type, tuberculatus-type, and viridis-type. On the other hand, seed features are not useful for other species, for example, those included in the deflexus-type (A. deflexus, A. vulgatissimus, A. cacciatoi, A. spinosus, A. dubius, and A. stadleyanus). A diagnostic key of the studied taxa is proposed. Subgenera cannot be distinguished using seed features, thus confirming the published molecular data. All these facts reveal, once again, the taxonomic complexity of the genus Amaranthus since, e.g., just a few seed types can be defined.

Epidemiology of depression and anxiety among undergraduate students.

AIMS: Depression and anxiety are the most common and prevalent mental health issues among undergraduate students. This study aimed to investigate the prevalence of anxiety and depression, their associated predictors, and to assess knowledge and use of antidepressant medications among university students in Jordan. METHODS: A cross-sectional survey-based study was conducted in Jordan among undergraduate students from all levels of study. Istilli et al's questionnaire, the PHQ-9 and generalised anxiety disorder (GAD) scales were used in this study to explore the study objectives. Logistic regression analysis was used to identify predictors of anxiety and depression. RESULTS: A total of 1582 undergraduate students participated in the study. Prevalence of depression was 22.3% (n = 330), with proportions of minimal, mild, moderate, moderately severe and severe depression to be 15.9%, 32.4%, 29.5%, 14.7% and 7.6%, respectively. Prevalence of anxiety was 15.8% (n = 173), with proportions of mild, moderate and severe anxiety to be 46.4%, 37.8% and 15.8%, respectively. Female students and those with low income (<500 JD) had higher depression mean scores compared with others. Females, arts and engineering students, divorced and those who have four or more children had higher anxiety mean scores compared with others. CONCLUSION: Findings of this study addressed the importance of taking serious measures and interventions to prevent the development of severe mental illness among university students.

Medications disposal and medications storage in Jordan: A cross-sectional study.

AIMS: Many concerns arise from the improper disposal of medications, which is associated with a negative impact on health and wildlife. The majority of the consumers of pharmaceutical products remain unaware of the procedures of disposal of unused or expired medicines. This study aimed to explore the practices of Jordanian individuals regarding the disposal and storage of unused or expired medications. METHODS: A cross-sectional study was conducted in Jordan for the period between July and November 2019 of patients who reported having unused, leftover or expired medications in their homes. The questionnaire tool was constructed based on a number of studies concerning medication recycling and international guidelines about correct and safe disposal of expired, unwanted or unused medication. RESULTS: A total of 1092 participants were included in the study. Their mean age was 32.4 (SD = 13.6) years and 56.8% (n = 620) were males. More than half of the participants (58.1%, n = 634) reported that they had unused, leftover or expired medications in their homes. The bedroom, kitchen and store room were the three most commonly reported places for the storage of unused, leftover or expired medications. The pharmacist was the main source for information regarding the storage of medications. The three most common reasons reported by the participants regarding having unused/leftover medications at home were change or discontinuation by the doctor (29.4%), self-discontinuation as the illness symptoms improved or resolved (28.2%) and forgetfulness (25.1%). CONCLUSION: A high percentage of the Jordanian population improperly handles their unused, leftover or expired medications. More restrictions are needed on the prescribing and dispensing of medications by the authorities concerned and there is a need to establish public guidelines regarding the use and correct disposal of pharmaceuticals.

Association of 25-hydroxyvitamin D with HDL-cholesterol and other cardiovascular risk biomarkers in subjects with non-cardiac chest pain.

BACKGROUND: Chest pain is a serious symptom that is routinely investigated as a sign of coronary artery disease. Non-cardiac chest pain (NCCP) is indistinguishable from ischemic chest pain and both are considered serious and receive similar medical investigations. Although NCCP is not associated with cardiovascular diseases (CVDs), patients with NCCP may become anxious and frightened from developing coronary events. So, it will be valuable to improve modifiable cardiovascular risk factors in such subjects to reduce fear from CVDs. Because vitamin D deficiency was considered as a possible modifiable cardiovascular risk factor, our aim was to investigate association between serum vitamin D and cardiovascular risk variables in subjects with NCCP. METHODS: A cross-sectional study involved 104 subjects who underwent cardiac catheterization that did not reveal any cardiac origin for their chest pain. 25-hydroxyvitamin D was measured by electrochemiluminescence immunoassay, glucose was measured by hexokinase method, hemoglobin A1c (HbA1c) was measured by turbidimetric inhibition immunoassay and lipid profile was measured by enzymatic colorimetric assays. RESULTS: High density lipoprotein cholesterol (HDL-C) was significantly higher in subjects with sufficient vitamin D compared to those with insufficient or deficient vitamin D (p-value< 0.01). 25-hydroxyvitamin D was positively associated with HDL-C (p-value< 0.01) and inversely associated with HbA1c (p-value = 0.02). 25-hydroxyvitamin D was not significantly correlated with other cardiovascular biomarkers including blood pressure, glucose, and other components of lipid profile (p-values> 0.05). CONCLUSIONS: low serum vitamin D could be involved in reducing HDL-C and increasing HbA1c and thus it may increase cardiovascular risk in subjects with NCCP.

Non-cardiac Chest Pain and Anxiety: A Possible Link to Vitamin D and Calcium.

This study was performed to check the hypothesis that low serum vitamin D and reduced calcium intake may contribute to the comorbidity of psychological symptoms (anxiety and depression) and non-cardiac chest pain (NCCP). The design was a case-control study that involved 40 subjects with NCCP and 40 age and gender-matched healthy controls. Serum vitamin D was assessed using electrochemiluminescence immunoassay; anxiety and depression symptoms were assessed using Hospital Anxiety and Depression Scale, and dietary calcium intake was assessed by self-reporting. Subjects with NCCP had higher anxiety and depression scores and lower vitamin D and dietary calcium intake compared to healthy controls (p < .05). NCCP was associated with anxiety score (odds ratio = 1.40, p < .01). Prevalence of abnormal anxiety score was much higher in subjects with NCCP (47.5%) compared to healthy controls (7.5%). Anxiety score was inversely correlated with vitamin D level and dietary calcium intake (p < .01). Anxiety score was inversely associated with vitamin D level (R2 = .32, p < .05). In conclusion, development of NCCP can be predicted from increased anxiety score which in turn can be predicted from low vitamin D levels. This suggests physicians to consider anxiety and vitamin D deficiency as possible causes for NCCP.

Comparative SEM and LM foliar epidermal and palyno-morphological studies of Amaranthaceae and its taxonomic implications.

Palynological features as well as comparative foliar epidermal using light and scanning electron microscope (SEM) of 17 species (10genera) of Amaranthaceae have been studied for its taxonomic significance. Different foliar and palynological micro-morphological characters were examined to explain their value in resolving the difficulty in identification. All species were amphistomatic but stomata on abaxial surface were more abundant. Taxonomically significant epidermal character including stomata type, trichomes (unicellular, multicellular, and capitate) and epidermal cells shapes (polygonal and irregular) were also observed. Pollens of this family are Polypantoporate, pores large, spheroidal, mesoporous region is sparsely to scabrate, densely psilate, and spinulose. All these characters can be active at species level for identification purpose. This study indicates that at different taxonomic levels, LM and SEM pollen and epidermal morphology is explanatory and significant to identify species and genera.