Liver is constantly exposed to pathogens, viruses, chemicals, and toxins, and several of them cause injury, leading to the loss of liver mass and sometimes resulting in cirrhosis and cancer. Under ...physiological conditions, liver can regenerate if the loss of cells is less than the proliferation of hepatocytes. If the loss is more than the proliferation, the radical treatment available is liver transplantation. Due to this reason, the search for an alternative therapeutic agent has been the focus of liver research. Liver regeneration is regulated by several growth factors; one of the key factors is augmenter of liver regeneration (ALR). Involvement of ALR has been reported in crucial processes such as oxidative phosphorylation, maintenance of mitochondria and mitochondrial biogenesis, and regulation of autophagy and cell proliferation. Augmenter of liver regeneration has been observed to be involved in liver regeneration by not only overcoming cell cycle inhibition but by maintaining the stem cell pool as well. These observations have created curiosity regarding the possible role of ALR in maintenance of liver health. Thus, this review brings a concise presentation of the work done in areas exploring the role of ALR in normal liver physiology and in liver health maintenance by fighting liver diseases, such as liver failure, non‐alcoholic fatty liver disease/non‐alcoholic steatohepatitis, viral infections, cirrhosis, and hepatocellular carcinoma.
The aim of this systematic review and meta-analysis was to summarize and compare the available evidence on the level of vitamin D and antioxidant trace elements between the keratoconus (KC) patients ...and healthy controls. Seven case-control studies with 830 subjects were found eligible with a systematic search using PubMed, SCOPUS, Web of Science, and EMBASE till November 21, 2021. Data were synthesized with a DerSimonian and Laird random-effects method of meta-analysis. The mean serum vitamin D level was significantly lower in the patients with KC standardized mean difference (SMD): −0.71; P < 0.001 as compared with the control group. The mean serum vitamin D level decreased more in the progressive patients (SMD: −0.80; P = 0.016) than in the stable patients (SMD: −0.66; P < 0.001) when compared with the control group. The mean serum zinc level was found significantly lower in the patients with KC compared with the control group (SMD: −1.98; P = 0.005). Pooled analysis based on the two studies showed significantly lower mean selenium levels in the KC patients (SMD: −0.34; P = 0.003). Regular evaluation of serum vitamin D, zinc, and selenium levels among the patients with KC at disease onset and future follow-ups could be promising in predicting the progressive disease and disease severity.
HER2 is an oncogene, expression of which leads to poor prognosis in 30% of breast cancer patients. Although trastuzumab is apparently an effective therapy against HER2-positive tumors, its systemic ...toxicity and resistance in the majority of patients restricts its applicability. In this study we evaluated the effects of phenethyl isothiocyanate (PEITC) in HER2-positive breast cancer cells.
MDA-MB-231 and MCF-7 breast cancer cells stably transfected with HER2 (high HER2 (HH)) were used in this study. The effect of PEITC was evaluated using cytotoxicity and apoptosis assay in these syngeneic cells. Western blotting was used to delineate HER2 signaling. SCID/NOD mice were implanted with MDA-MB-231 (HH) xenografts.
Our results show that treatment of MDA-MB-231 and MCF-7 cells with varying concentrations of PEITC for 24 h extensively reduced the survival of the cells with a 50% inhibitory concentration (IC50) of 8 μM in MDA-MB-231 and 14 μM in MCF-7 cells. PEITC treatment substantially decreased the expression of HER2, epidermal growth factor receptor (EGFR) and phosphorylation of signal transducer and activator of transcription 3 (STAT3) at Tyr-705. The expression of BCL-2-associated × (BAX) and BIM proteins were increased, whereas the levels of B cell lymphoma-extra large (BCL-XL) and X-linked inhibitor of apoptosis protein (XIAP) were significantly decreased in both the cell lines in response to PEITC treatment. Substantial cleavage of caspase 3 and poly-ADP ribose polymerase (PARP) were associated with PEITC-mediated apoptosis in MDA-MB-231 and MCF-7 cells. Notably, transient silencing of HER2 decreased and overexpressing HER2 increased the effects of PEITC. Furthermore, reactive oxygen species (ROS) generation, mitochondrial depolarization and apoptosis by PEITC treatment were much higher in breast cancer cells expressing higher levels of HER2 (HH) as compared to parent cell lines. The IC50 of PEITC following 24 h of treatment was reduced remarkably to 5 μM in MDA-MB-231 (HH) and 4 μM in MCF-7 (HH) cells, stably overexpressing HER2. Oral administration of 12 μM PEITC significantly suppressed the growth of breast tumor xenografts in SCID/NOD mice. In agreement with our in vitro results, tumors from PEITC-treated mice demonstrated reduced HER2, EGFR and STAT3 expression and increased apoptosis as revealed by cleavage of caspase 3 and PARP. In addition our results show that PEITC can enhance the efficacy of doxorubicin.
Our results show a unique specificity of PEITC in inducing apoptosis in HER2-expressing tumor cells in vitro and in vivo and enhancing the effects of doxorubicin. This unique specificity of PEITC offers promise to a subset of breast cancer patients overexpressing HER2.
The epidemiological evidence suggests a strong inverse relationship between dietary intake of cruciferous vegetables and the incidence of cancer. Among other constituents of cruciferous vegetables, ...isothiocyanates (ITC) are the main bioactive chemicals present. Phenethyl isothiocyanate (PEITC) is present as gluconasturtiin in many cruciferous vegetables with remarkable anti-cancer effects. PEITC is known to not only prevent the initiation phase of carcinogenesis process but also to inhibit the progression of tumorigenesis. PEITC targets multiple proteins to suppress various cancer-promoting mechanisms such as cell proliferation, progression and metastasis. Pre-clinical evidence suggests that combination of PEITC with conventional anti-cancer agents is also highly effective in improving overall efficacy. Based on accumulating evidence, PEITC appears to be a promising agent for cancer therapy and is already under clinical trials for leukemia and lung cancer. This is the first review which provides a comprehensive analysis of known targets and mechanisms along with a critical evaluation of PEITC as a future anti-cancer agent.
•Epidemiological evidence shows reduced cancer incidence with intake of cruciferous vegetables.•PEITC from cruciferous vegetables acts as preventive as well as therapeutic agent against cancer via different mechanisms.•PEITC has multi-targeted effects and hence acts through all the different hallmarks of cancer.•PEITC can potentiate the anti-cancer effects of conventional chemo-agents.•PEITC is in clinical trials for oral and lung cancer.
Cataract surgery requires a well-dilated and stable pupil for a good outcome. Unexpected pupillary constriction during surgery increases the risk of complication. This problem is more pronounced in ...children. There are now pharmacological interventions that help tackle this unforeseen happening. Our review discusses the simple and quick options available to a cataract surgeon when faced with this dilemma. As cataract surgical techniques continue to improvise and get faster, an adequate pupil size is of paramount importance. Various topical and intra-cameral drugs are used in combination to achieve mydriasis. Despite good pre-operative dilation, the pupil can be quite unpredictable during surgery. Intra-operative miosis limits the field of surgery and increases the risk of complications. For example, if the pupil size decreases from 7 mm to 6 mm, this 1 mm change in pupil diameter will lead to a decrease of 10.2 mm2 in the area of surgical field. Making a good capsulorhexis with a small pupil can be a challenge, even for an experienced surgeon. Repeated touching of the iris increases the risk of fibrinous complications. Removal of cataract and the cortical matter becomes increasingly difficult. Intra-ocular lens implantation in the bag also requires adequate dilation. When dealing with challenging cases like lens subluxation, pseudo-exfoliation, and zonular dehiscence, a small pupil further increases the risk and adversely affects the surgical outcome. Hence, achieving and maintaining adequate mydriasis throughout surgery is essential. This review highlights the risk factors for small pupils during surgery and current management strategies.
The rising level of childhood obesity across the globe has escalated the worries of World Health Organization (WHO), health practitioners, policymakers, and regulators. One of the most prominent ...factors that promote unhealthy eating habits of children is the heavy advertising of food and beverages (F and B) targeted at children. This has deepened the concerns of stakeholders about the persuasion ethics of firms aggressively promoting unhealthy foodstuff to young consumers. This article presents a systematic literature review of scholarly research on the advertising of unhealthy F and B targeted at children. A systematic review of 70 peer-reviewed articles is conducted through the theoretical lens to present their contributions. Synthesising the findings of empirical studies, the scholarly research is classified into six core research themes. We elaborate on directions for future research: Theory, Context, and Methods and distil specific research questions for future studies.
Cancer is a multistep process resulting in uncontrolled cell division. It results from aberrant signaling pathways that lead to uninhibited cell division and growth. Various recent epidemiological ...studies have indicated that consumption of cruciferous vegetables, such as garden cress, broccoli, etc., reduces the risk of cancer. Isothiocyanates (ITCs) have been identified as major active constituents of cruciferous vegetables. ITCs occur in plants as glucosinolate and can readily be derived by hydrolysis. Numerous mechanistic studies have demonstrated the anticancer effects of ITCs in various cancer types. ITCs suppress tumor growth by generating reactive oxygen species or by inducing cycle arrest leading to apoptosis. Based on the exciting outcomes of preclinical studies, few ITCs have advanced to the clinical phase. Available data from preclinical as well as available clinical studies suggest ITCs to be one of the promising anticancer agents available from natural sources. This is an up‐to‐date exhaustive review on the preventive and therapeutic effects of ITCs in cancer.