Catharanthus roseus-assisted bio-fabricated zinc oxide nanoparticles for promising antibacterial potential against Klebsiella pneumoniae.

This study emphasized on the synthesis of zinc oxide nanoparticles (ZnO NPs) in an environmentally friendly manner from the extract of Catharanthus roseus leaves and its antibacterial assessment against the pneumonia-causing pathogen Klebsiella pneumoniae. This simple and convenient phytosynthesis approach is found to be beneficial over conventional methods, wherein plants serve as excellent reducing, capping, and stabilizing agents that enables the formation of ZnO NPs without the use of harmful chemicals. The formation of ZnO NPs was confirmed through several characterization techniques such as UV-visible spectroscopy, XRD, FT-IR, SEM, HR-TEM, and EDX. XRD analysis revealed high polycrystallinity with crystallite size of approximately 13 nm. SEM and HR-TEM revealed the hexagonal structure of ZnO NPs with the particle size range of 20-50 nm. The EDX shows the elemental purity without any impurity. Furthermore, the antibacterial efficacy by the technique of disc diffusion exhibited clear inhibition zones in ZnO NPs-treated discs. In addition, 125 µg/mL of ZnO NP concentration showed minimum inhibition by the microbroth dilution method. The potent inhibitory activity was further validated with trypan blue dye exclusion and fluorescence microscopy. Finally, SEM examination confirmed the efficient antibacterial potential of ZnO NPs through disruption of the intact morphology of Klebsiella pneumoniae.

Appraisal of the Antioxidant Activity, Polyphenolic Content, and Characterization of Selected Himalayan Herbs: Anti-Proliferative Potential in HepG2 Cells.

Natural antioxidants derived from plants have played a vital role in preventing a wide range of human chronic conditions and provide novel bioactive leads for investigators in pharmacotherapy discovery. This work was designed to examine the ethnopharmacological role of Urtica dioica (UD), Capsella bursa-pastoris (CBP), and Inula racemosa (IR). The total phenolic and flavonoid contents (TPC and TFC) were illustrated through colorimetric assays, while the antioxidant activity was investigated through DPPH and ABTS assays. The evaluation of phytochemicals by FT-IR of UD and CBP revealed high contents of aliphatic amines, while IR showed a major peak for ketones. The antioxidant activity, TPC and TFC were highest in the ethanol extract of UD, followed by CBP, and IR showed the lowest activity. All of the extracts revealed significant antioxidant capacities along a dosage gradient. Through a HPLC analysis at a wavelength of 280 nm, UD leaves demonstrated an intense peak of quercetin, and the peak for rutin was less intense. CBP (whole plant), instead, demonstrated a major yield of rutin, and a peak for quercetin was not observed in CBP. IR (rhizomes) showed both quercetin and rutin. All of the extracts were significantly cytotoxic to HepG2 cells after 48 h with the trend IR > UD > CBP. The outcomes of this study may be effective in the selection of specific plants as realistic sources of the bioactive components that might be useful in the nutraceutical progression and other biomedical efficacies.

Stearoyl-CoA Desaturase (SCD) Induces Cardiac Dysfunction with Cardiac Lipid Overload and Angiotensin II AT1 Receptor Protein Up-Regulation.

Heart failure is a major cause of death worldwide with insufficient treatment options. In the search for pathomechanisms, we found up-regulation of an enzyme, stearoyl-CoA desaturase 1 (Scd1), in different experimental models of heart failure induced by advanced atherosclerosis, chronic pressure overload, and/or volume overload. Because the pathophysiological role of Scd1/SCD in heart failure is not clear, we investigated the impact of cardiac SCD upregulation through the generation of C57BL/6-Tg(MHCSCD)Sjaa mice with myocardium-specific expression of SCD. Echocardiographic examination showed that 4.9-fold-increased SCD levels triggered cardiac hypertrophy and symptoms of heart failure at an age of eight months. Tg-SCD mice had a significantly reduced left ventricular cardiac ejection fraction of 25.7 ± 2.9% compared to 54.3 ± 4.5% of non-transgenic B6 control mice. Whole-genome gene expression profiling identified up-regulated heart-failure-related genes such as resistin, adiponectin, and fatty acid synthase, and type 1 and 3 collagens. Tg-SCD mice were characterized by cardiac lipid accumulation with 1.6- and 1.7-fold-increased cardiac contents of saturated lipids, palmitate, and stearate, respectively. In contrast, unsaturated lipids were not changed. Together with saturated lipids, apoptosis-enhancing p53 protein contents were elevated. Imaging by autoradiography revealed that the heart-failure-promoting and membrane-spanning angiotensin II AT1 receptor protein of Tg-SCD hearts was significantly up-regulated. In transfected HEK cells, the expression of SCD increased the number of cell-surface angiotensin II AT1 receptor binding sites. In addition, increased AT1 receptor protein levels were detected by fluorescence spectroscopy of fluorescent protein-labeled AT1 receptor-Cerulean. Taken together, we found that SCD promotes cardiac dysfunction with overload of cardiotoxic saturated lipids and up-regulation of the heart-failure-promoting AT1 receptor protein.

Pregnancy-associated osteoporosis: a UK case series and literature review.

Mini Abstract: Pregnancy-associated osteoporosis (PAO) is a rare syndrome affecting women during late pregnancy and the early postpartum period. We set out to review the clinical features of ten cases of PAO from a single UK centre. Patients had attended the Royal National Hospital for Rheumatic Diseases, Bath (RNHRD) between January 2000 and June 2016. The principal criterion for inclusion was the occurrence of low trauma fractures either during pregnancy or the immediate post-partum period. Data were obtained from retrospective review of medical notes. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (Hologic ®Discovery system) at the lumbar spine and hip. Data pertaining to the pregnancy, as well as type and duration of treatment received, were reviewed. All ten cases presented with vertebral fractures. In four patients, no risk factors for fracture other than pregnancy or breastfeeding could be identified. Four patients were found to have vitamin D insufficiency at the time of diagnosis, and a further two patients had received treatment with low molecular weight heparin (LMWH). In one case, further investigation led to a diagnosis of osteogenesis imperfecta (OI) confirmed on genetic testing. In terms of treatment, eight out of the ten patients in this series received a bisphosphonate, most commonly risedronate due to its relatively short skeletal retention time. Clinicians should be aware of PAO, a rare but recognised complication of pregnancy. The condition should be especially considered in women presenting with new onset back pain in pregnancy or the postpartum period.

The effect of cavity disinfectants on microleakage of composite restorations in primary teeth.

AIM: The purpose of this study was to determine the effect of different cavity disinfectants on microleakage of Class V resin- based composite restorations in primary teeth. MATERIALS AND METHODS: Standard non-beveled Class V cavities were prepared on 50 human primary anterior teeth with the incisal and cervical margin placed on the enamel. The crowns were randomly divided into 6 groups. Four experimental groups of 10 teeth each, in which cavities were disinfected using the following solutions: 1) S. persica extract (Ethanol 1 mg/ml); 2) 1.3% sodium hypochlorite (NaOCl); 3) 0.2% chlorhexidine gluconate (CHX), and 4) No solution applied. Two control groups; 5 teeth each; 5) Negative control: filled cavity and entirely coated with nail varnish and 6) positive control: empty cavity and without nail varnish coating. Each cavity in groups 1-5 were filled with Filtek Z350 XT Universal Restorative (3M Espe, St. Paul, USA). All specimens were thermocycled for 500 cycles (5°C/55°C) and prepared for microleakage evaluation using a 2% methylene blue. RESULTS: For the experimental groups; there was no significant difference in dye penetration between the incisal and cervical walls in all groups (P=0.176). However comparing microleakage by location/walls showed a significant difference in dye penetration between the incisal walls (P=0.014) and cervical walls (P=.045). CONCLUSIONS: None of the disinfectant solutions in the experimental groups were able to prevent dye penetration. In comparison to chlorhexidine gluconate and sodium hypochlorite; application of S. persica did not increase microleakage and was not detrimental to enamel and dentin adhesion using the restorative technique and materials used in this study.

Maternal separation influences hepatic drug-metabolizing CYP450 gene expression without pathological changes in adult mice.

OBJECTIVES: The principal motive of this study is to explore the influence maternal separation (MS) exhibits on the mRNA expression of major drug metabolizing-cyp450s in parallel with the assessment of pathological changes that can be induced by MS in the livers of experimental mice. METHODS: Eighteen Balb/c mouse pups, comprising of both males and females, were separated from their mothers after birth. Following a six-week period during when the pups became adults, the mice were sacrificed and their livers were isolated for analysis of weight, pathohistological alterations, and the mRNA expression of drug metabolizing cyp450 genes: cyp1a1, cyp3a11, cyp2d9, and cyp2c29. RESULTS: The study demonstrated that MS markedly downregulated (p<0.05) the mRNA expression of all tested drug-metabolizing cyp450s in livers of female and male mice. Furthermore, the mRNA levels of major drug-metabolizing cyp450s were notably lower (p<0.05) in livers of female MS mice as compared with male MS mice. It was found that values of the total body weight and liver weight of MS mice did not vary significantly (p>0.05) from those of the control groups. Additionally, histological examination revealed that the hepatic tissue of MS mice was normal, similar to that of the control mice. CONCLUSIONS: In summary, MS downregulates the gene expression of major hepatic drug-metabolizing cyp450s without inducing pathological alterations in the livers of mice. These findings provide an explanation for the heterogeneity in pharmacokinetics and drug response of patients with early life stress.

Myocardial infarction with normal coronaries: an unexpected finding in a 13-year-old girl with systemic lupus erythematosus.

We report a 13-year-old girl diagnosed with systemic lupus erythematosus (SLE) who presented with left-sided chest pain, with ECG changes and elevation troponins that were suggestive of an acute inferior wall myocardial infarction (MI). Her multi-slice computed tomography coronary angiogram and standard angiogram were normal. The cardiac magnetic resonance imaging revealed an area of infarcted myocardium that was in the right coronary artery territory. We believe her MI was most likely secondary to coronary vasospasm. MI is rare and coronary vasospasm is an uncommon cause of MI in children and adolescents with SLE.

Chronic intestinal pseudo-obstruction: a rare first manifestation of systemic lupus erythematosus.

Chronic intestinal pseudo-obstruction (CIPO) is a rare clinical syndrome of ineffective intestinal motility characterised by clinical and radiological evidence of intestinal obstruction with no identifiable mechanical lesion. CIPO can either be idiopathic or secondary to a systemic disease, like systemic lupus erythematosus (SLE). Fewer than 30 cases of CIPO secondary to SLE have been reported so far. Here we describe a case of SLE with the initial presentation of CIPO. In SLE-related CIPO, treatment includes a combination of high-dose intravenous corticosteroids, immunosuppressants and supportive care. With awareness of this condition, unnecessary surgical intervention and repeated invasive procedures could be avoided. Early initiation of treatment would avoid complications and bring about resolution of symptoms.

Painless ascites and elevated CA125: initial presentation of lupus-associated protein-losing enteropathy.

Lupus associated protein loosing enteropathy (LUPLE) is a rare gastrointestinal manifestation of SLE. We presented a case of painless ascites from serve hypoalbuminaemia secondary to LUPLE. The patient responded to a course of intravenous cyclophosphamide. The remission was maintained by azathioprine and low dose prednisolone.

The Safety and Effectiveness of mRNA Vaccines Against SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in numerous deaths worldwide, along with devastating economic disruptions, and has posed unprecedented challenges to healthcare systems around the world. In the wake of COVID-19's emergence in 2019, a variety of vaccine technologies were formulated and developed, including those that drew from the technology employed in messenger RNA (mRNA) vaccines, designed to curb the disease's transmission and manage the pandemic. mRNA vaccine has several advantages over traditional ones, and hence its development has received considerable attention recently. Researchers believe the mRNA vaccine technology will emerge as the leading technology because it is potent, inexpensive, rapidly developed, and safe. This article provides an overview of mRNA vaccines with a special focus on the efficacy and safety of the Moderna and Pfizer-BioNTech mRNA vaccines against the different variants of COVID-19 and compare them with the Oxford-AstraZeneca (viral vector) and Sinopharm (inactivated virus) vaccines. The clinical data reviewed in this article demonstrate that the currently authorized Moderna and Pfizer-BioNTech mRNA vaccines are highly safe and potent against different variants of COVID-19, especially in comparison with Oxford-AstraZeneca (viral vector) and Sinopharm (inactivated virus) vaccines.

Cryptosporidium species diagnosis in handlers of domestic pigeons in Baghdad City: Molecular and microscopic approaches.

Objective: The aim of this study is to detect the prevalence and diagnosis of molecular characteristics of Cryptosporidium infection in handlers of domestic pigeons in Baghdad City. Traditional and molecular diagnostic methods were employed to detect and identify Cryptosporidium species. Materials and methods: Sixty stool samples were collected from the handlers of domestic pigeons, and various techniques, including direct smear, flotation concentration, staining methods, and DNA extraction coupled with nested polymerase chain reaction (PCR), were utilized. Results: The results obtained from traditional methods indicated an overall infection rate of 55% in handlers of domestic pigeons, while significant variations were noted between male and female handlers. Age group 21-40 years were found to have higher infection rates were found to have higher infection rates. The prevalence of Cryptosporidium also displayed temporal variability throughout the study period. Molecular analysis using nested PCR revealed higher infection rates of 86% in handlers of domestic pigeon samples. Genotyping and phylogenetic analysis identified the presence of Cryptosporidium parvam species in handlers of domestic pigeons, indicating zoonotic transmission potential. Conclusion: These findings underscore the high prevalence of Cryptosporidium infection among handlers of domestic pigeons in Baghdad City.

The Incidence and Severity of COVID-19 Infection Post Vaccination in Saudi Arabia.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). Presently, there is ongoing continuous research for more therapeutic options with a wide variety of vaccine availability. However, many people have worried about the vaccine's side effects. Hence, the current study was conducted to determine the prevalence of vaccinated individuals, side effects, and the rate of infectivity post vaccination including the three doses of vaccinations. Methods A cross-sectional questionnaire-based survey was conducted using Google Forms (Google, Inc., Mountain View, CA). Five hundred forty-three individuals participated and reported their status of COVID-19 infection, vaccination, and side effects. All the participants from Saudi Arabia received all the vaccine shots including the booster dose. Results Most of the Saudi nationals were fully vaccinated, and most received Pfizer vaccines for their first and second shots. Pain at the injection site was reported as the most common adverse effect followed by fever, headache, fatigue, and joint pain. Conclusion From the findings, it is concluded that most of the population of Saudi Arabia was vaccinated effectively. Pain at the injection site is identified as the primary adverse effect of vaccination. Most of the population is vaccinated with the Pfizer vaccine. Long-term side effect monitoring is recommended with large population studies to confirm the status of vaccines and adverse effects.

Preparation and in vitro/in vivo characterization of sustained-release ciprofloxacin-carrageenan complex.

The goal of the study was to look into drug-polyelectrolyte complexation between ciprofloxacin (Cipro) and λ-carrageenan (CRG), and to employ the complex as a sustained-release matrix. The maximum binding capacity of the complexation was determined using the dialysis bag method and employed to prepare the complex. In comparison to Cipro, CRG, and their physical mixing, the complex was examined using differential scanning calorimetry, Fourier infrared spectroscopy, powder X-ray diffraction, and scanning electron microscopy. Cipro-CRG matrices, manufactured as direct compression tablets based on the greatest binding capacity, were assessed for swelling, erosion and drug release in 0.1 M HCl, in comparison with those of CRG, Hydroxypropyl methylcellulose (HPMC) and Cipro-HPMC matrices. In vivo absorption study comparing the Cipro-CRG matrix to Cipro immediate-release tablet was also carried out. The greatest binding capacity of Cipro to CRG was 55% (w/w). Multiple interactions, including electrostatic interaction, Vander wall forces, and hydrogen bonding, have been proposed to be involved in complexation with drug amorphization. As a result of the complexation, the swelling and erosion properties of CRG changed, with Cipro-CRG matrix showing substantially less swelling and erosion than Cipro-free CRG matrix. Cipro-CRG matrix exhibited swelling and erosion similar to Cipro-HPMC matrix. However, the former matrix demonstrated Cipro release with significantly less burst impact and a significantly slower release rate. Furthermore, Cipro-CRG matrices in vivo demonstrated slow-prolonged oral drug absorption with consequent significant changes in pharmacokinetic parameters in comparison to those obtained for immediate-release tablets.

Chlorogenic Acid Restores Ovarian Functions in Mice with Letrozole-Induced Polycystic Ovarian Syndrome Via Modulation of Adiponectin Receptor.

Around the world, polycystic ovary syndrome (PCOS) is a complex endocrine-metabolic condition that typically affects 6-20% of females. Our study's major goal was to examine how chlorogenic acid (CGA) affected mice with endocrine and metabolic problems brought on by letrozole-induced PCOS. Group I served as the control for 81 days; Group II was given Letrozole (LETZ) orally at a dose of 6 mg/kg bw for 21 days to induce PCOS; Group III was given LETZ (6 mg/kg) for 21 days, followed by treatment with CGA (50 mg/kg bw daily) for 60 days. The study indicated that LETZ-treated mice displayed symptoms of PCOS, such as dyslipidemia, hyperinsulinemia, elevated testosterone, increases in inflammatory markers and malonaldehyde, and a decline in antioxidants (Ar, lhr, fshr, and esr2) in the ovaries. These alterations were affected when the mice were given CGA and were associated with reduced levels of adiponectin. Adiponectin showed interactions with hub genes, namely MLX interacting protein like (MLXIPL), peroxisome proliferator-activated receptor gamma Coactivator 1- alpha (PPARGC1), peroxisome proliferator-activated receptor gamma (Pparg), and adiponectin receptor 1 (Adipor1). Lastly, the gene ontology of adiponectin revealed that adiponectin was highly involved in biological processes. The findings from our research suggest that adiponectin has direct impacts on metabolic and endocrine facets of PCOS.

Prospective Epigenetic Actions of Organo-Sulfur Compounds against Cancer: Perspectives and Molecular Mechanisms.

Major epigenetic alterations, such as chromatin modifications, DNA methylation, and miRNA regulation, have gained greater attention and play significant roles in oncogenesis, representing a new paradigm in our understanding of cancer susceptibility. These epigenetic changes, particularly aberrant promoter hypermethylation, abnormal histone acetylation, and miRNA dysregulation, represent a set of epigenetic patterns that contribute to inappropriate gene silencing at every stage of cancer progression. Notably, the cancer epigenome possesses various HDACs and DNMTs, which participate in the histone modifications and DNA methylation. As a result, there is an unmet need for developing the epigenetic inhibitors against HDACs and DNMTs for cancer therapy. To date, several epigenetically active synthetic inhibitors of DNA methyltransferases and histone deacetylases have been developed. However, a growing body of research reports that most of these synthetic inhibitors have significant side effects and a narrow window of specificity for cancer cells. Targeting tumor epigenetics with phytocompounds that have the capacity to modulate abnormal DNA methylation, histone acetylation, and miRNAs expression is one of the evolving strategies for cancer prevention. Encouragingly, there are many bioactive phytochemicals, including organo-sulfur compounds that have been shown to alter the expression of key tumor suppressor genes, oncogenes, and oncogenic miRNAs through modulation of DNA methylation and histones in cancer. In addition to vitamins and microelements, dietary phytochemicals such as sulforaphane, PEITC, BITC, DADS, and allicin are among a growing list of naturally occurring anticancer agents that have been studied as an alternative strategy for cancer treatment and prevention. Moreover, these bioactive organo-sulfur compounds, either alone or in combination with other standard cancer drugs or phytochemicals, showed promising results against many cancers. Here, we particularly summarize and focus on the impact of specific organo-sulfur compounds on DNA methylation and histone modifications through targeting the expression of different DNMTs and HDACs that are of particular interest in cancer therapy and prevention.

Deciphering the emerging role of phytocompounds: Implications in the management of drug-resistant tuberculosis and ATDs-induced hepatic damage.

Tuberculosis is a disease of poverty, discrimination, and socioeconomic burden. Epidemiological studies suggest that the mortality and incidence of tuberculosis are unacceptably higher worldwide. Genomic mutations in embCAB, embR, katG, inhA, ahpC, rpoB, pncA, rrs, rpsL, gyrA, gyrB, and ethR contribute to drug resistance reducing the susceptibility of Mycobacterium tuberculosis to many antibiotics. Additionally, treating tuberculosis with antibiotics also poses a serious risk of hepatotoxicity in the patient's body. Emerging data on drug-induced liver injury showed that anti-tuberculosis drugs remarkably altered levels of hepatotoxicity biomarkers. The review is an attempt to explore the anti-mycobacterial potential of selected, commonly available, and well-known phytocompounds and extracts of medicinal plants against strains of Mycobacterium tuberculosis. Many studies have demonstrated that phytocompounds such as flavonoids, alkaloids, terpenoids, and phenolic compounds have antibacterial action against Mycobacterium species, inhibiting the bacteria's growth and replication, and sometimes, causing cell death. Phytocompounds act by disrupting bacterial cell walls and membranes, reducing enzyme activity, and interfering with essential metabolic processes. The combination of these processes reduces the overall survivability of the bacteria. Moreover, several phytochemicals have synergistic effects with antibiotics routinely used to treat TB, improving their efficacy and decreasing the risk of resistance development. Interestingly, phytocompounds have been presented to reduce isoniazid- and ethambutol-induced hepatotoxicity by reversing serum levels of AST, ALP, ALT, bilirubin, MDA, urea, creatinine, and albumin to their normal range, leading to attenuation of inflammation and hepatic necrosis. As a result, phytochemicals represent a promising field of research for the development of new TB medicines.

Reviewing the Prospective Pharmacological Potential of Isothiocyanates in Fight against Female-Specific Cancers.

Gynecological cancers are the most commonly diagnosed malignancies in females worldwide. Despite the advancement of diagnostic tools as well as the availability of various therapeutic interventions, the incidence and mortality of female-specific cancers is still a life-threatening issue, prevailing as one of the major health problems worldwide. Lately, alternative medicines have garnered immense attention as a therapeutic intervention against various types of cancers, seemingly because of their safety profiles and enhanced effectiveness. Isothiocyanates (ITCs), specifically sulforaphane, benzyl isothiocyanate, and phenethyl isothiocyanate, have shown an intriguing potential to actively contribute to cancer cell growth inhibition, apoptosis induction, epigenetic alterations, and modulation of autophagy and cancer stem cells in female-specific cancers. Additionally, it has been shown that ITCs plausibly enhance the chemo-sensitization of many chemotherapeutic drugs. To this end, evidence has shown enhanced efficacy in combinatorial regimens with conventional chemotherapeutic drugs and/or other phytochemicals. Reckoning with these, herein, we discuss the advances in the knowledge regarding the aspects highlighting the molecular intricacies of ITCs in female-specific cancers. In addition, we have also argued regarding the potential of ITCs either as solitary treatment or in a combinatorial therapeutic regimen for the prevention and/or treatment of female-specific cancers. Hopefully, this review will open new horizons for consideration of ITCs in therapeutic interventions that would undoubtedly improve the prognosis of the female-specific cancer clientele. Considering all these, it is reasonable to state that a better understanding of these molecular intricacies will plausibly provide a facile opportunity for treating these female-specific cancers.

A Current Landscape on Alport Syndrome Cases: Characterization, Therapy and Management Perspectives.

Alport syndrome (AS) is a rare genetic disorder categorized by the progressive loss of kidney function, sensorineural hearing loss and eye abnormalities. It occurs due to mutations in three genes that encode for the alpha chains of type IV collagen. Globally, the disease is classified based on the pattern of inheritance into X-linked AS (XLAS), which is caused by pathogenic variants in COL4A5, representing 80% of AS. Autosomal recessive AS (ARAS), caused by mutations in either COL4A3 or COL4A4, represents 15% of AS. Autosomal dominant AS (ADAS) is rare and has been recorded in 5% of all cases due to mutations in COL4A3 or COL4A4. This review provides updated knowledge about AS including its clinical and genetic characteristics in addition to available therapies that only slow the progression of the disease. It also focuses on reported cases in Saudi Arabia and their prevalence. Moreover, we shed light on advances in genetic technologies like gene editing using CRISPR/Cas9 technology, the need for an early diagnosis of AS and managing the progression of the disease. Eventually, we provide a few recommendations for disease management, particularly in regions like Saudi Arabia where consanguineous marriages increase the risk.

Reactive oxygen species mediated apoptotic death of colon cancer cells: therapeutic potential of plant derived alkaloids.

Colorectal cancer (CRC) is one of the most deaths causing diseases worldwide. Several risk factors including hormones like insulin and insulin like growth factors (e.g., IGF-1) have been considered responsible for growth and progression of colon cancer. Though there is a huge advancement in the available screening as well as treatment techniques for CRC. There is no significant decrease in the mortality of cancer patients. Moreover, the current treatment approaches for CRC are associated with serious challenges like drug resistance and cancer re-growth. Given the severity of the disease, there is an urgent need for novel therapeutic agents with ideal characteristics. Several pieces of evidence suggested that natural products, specifically medicinal plants, and derived phytochemicals may serve as potential sources for novel drug discovery for various diseases including cancer. On the other hand, cancer cells like colon cancer require a high basal level of reactive oxygen species (ROS) to maintain its own cellular functions. However, excess production of intracellular ROS leads to cancer cell death via disturbing cellular redox homeostasis. Therefore, medicinal plants and derived phytocompounds that can enhance the intracellular ROS and induce apoptotic cell death in cancer cells via modulating various molecular targets including IGF-1 could be potential therapeutic agents. Alkaloids form a major class of such phytoconstituents that can play a key role in cancer prevention. Moreover, several preclinical and clinical studies have also evidenced that these compounds show potent anti-colon cancer effects and exhibit negligible toxicity towards the normal cells. Hence, the present evidence-based study aimed to provide an update on various alkaloids that have been reported to induce ROS-mediated apoptosis in colon cancer cells via targeting various cellular components including hormones and growth factors, which play a role in metastasis, angiogenesis, proliferation, and invasion. This study also provides an individual account on each such alkaloid that underwent clinical trials either alone or in combination with other clinical drugs. In addition, various classes of phytochemicals that induce ROS-mediated cell death in different kinds of cancers including colon cancer are discussed.

Antiulcer activity of methanol extract of Melastoma malabathricum leaves in rats.

OBJECTIVE: To determine the potential antiulcer activity of methanol extract of Melastoma malabathricum leaves (MEMM) using various established rat models. MATERIALS AND METHODS: Ten groups of rats were used and orally administered 10% DMSO (negative control), 100 mg/kg ranitidine (positive control) or MEMM (50, 250 and 500 mg/kg) followed by gastric ulcer induction either using ethanol or indomethacin. The stomachs were collected and subjected to macroscopic and microscopic analyses. RESULTS: MEMM exhibited significant (p < 0.05) antiulcer activity in the ethanol, but not in the indomethacin-induced gastric ulcer model. The percentage of antiulcer activity for 50-500 mg/kg MEMM ranged between 3 and 75%, respectively. The gross observations were supported by histological findings. MEMM also aggravated the indomethacin-induced gastric ulcer, leading to an increase in ulcer area formation and ulcer score. CONCLUSION: The M. malabathricum leaves showed antiulcer activity, which could be attributed to their antioxidant and anti-inflammatory activities. This requires further in-depth studies.