Putting the Brakes on Tumorigenesis with Natural Products of Plant Origin: Insights into the Molecular Mechanisms of Actions and Immune Targets for Bladder Cancer Treatment.

Bladder cancer is the 10th most commonly diagnosed cancer worldwide. Although the incidence in men is 4 times higher than that in women, the diagnoses are worse for women. Over the past 30 years, the treatment for bladder cancer has not achieved a significant positive effect, and the outlook for mortality rates due to muscle-invasive bladder cancer and metastatic disease is not optimistic. Phytochemicals found in plants and their derivatives present promising possibilities for cancer therapy with improved treatment effects and reduced toxicity. In this study, we summarize the promising natural products of plant origin with anti-bladder cancer potential, and their anticancer mechanisms-especially apoptotic induction-are discussed. With the developments in immunotherapy, small-molecule targeted immunotherapy has been promoted as a satisfactory approach, and the discovery of novel small molecules against immune targets for bladder cancer treatment from products of plant origin represents a promising avenue of research. It is our hope that this could pave the way for new ideas in the fields of oncology, immunology, phytochemistry, and cell biology, utilizing natural products of plant origin as promising drugs for bladder cancer treatment.

Clinical and in vitro analysis of Osteopontin as a prognostic indicator and unveil its potential downstream targets in bladder cancer.

Osteopontin (OPN) plays an important role in cancer progression, however its prognostic significance and its downstream factors are largely elusive. In this study, we have shown that expression of OPN was significantly higher in bladder cancer specimens with higher T-stage or tumor grades. In addition, a high level of OPN was significantly associated with poorer survival in two independent bladder cancer patient cohorts totaling 389 bladder cancer patients with available survival data. We further identified Matrix metallopeptidase 9 (MMP9) and S100 calcium-binding protein A8 (S100A8) were both downstream factors for OPN in bladder cancer specimens and bladder cancer cell lines. Expression of OPN was significantly positively associated with that of MMP9 and S100A8, while overexpression of OPN resulted in upregulation of MMP9 and S100A8, and knockdown of OPN showed consistent downregulation of MMP9 and S100A8 expression levels. Importantly, expression levels of both MMP9 and S100A8 were significantly associated with higher T-stage, higher tumor grade and a shorter survival time in the bladder cancer patients. Interestingly, OPN expression only predicted survival in MMP9-high, but not MMP9-low subgroups, and in S100A8-low but not S100A8-high subgroups. Our results suggest that OPN, MMP9 and S100A8 all play a significant role in bladder cancer progression and are potential prognostic markers and therapeutic targets in bladder cancer. The mechanistic link between these three genes and bladder cancer progression warrants further investigation.

Venom Peptides and Toxins - A Prospective Spearhead in Cancer Treatment.

BACKGROUND & AIM: Cancer is a condition of genetically or environmentally mutated, uncontrollable cell growth that directly affects human morbidity and mortality. Many treatments have been adopted to reduce cancer cell proliferation; however, new mutated developments of some cancer cells have started to show resistance towards current therapies and treatments that cause some drugs to lose their efficacy. Additionally, deleterious side-effects of some hard application methods like radiation therapy, chemotherapy, and surgery are less favorable. Accumulative research effort has revealed that peptides and toxins identified from underutilized natural sources including venomous reptiles, amphibians, insects, arachnids, marine organisms and plants are increasingly being employed in cancer treatment. This demands more peptides / toxins to be identified from underutilized natural sources as an alternative therapeutic approach. METHOD & RESULTS: Accumulative research effort has revealed that peptides and toxins identified from underutilized natural sources including venomous reptiles, amphibians, insects, arachnids, marine organisms and plants are increasingly being employed in cancer treatment. Secondary structures / pharmacophore modifications have proven to be an important criterion for raising the efficacy level and anticancer effects. Structure specificity and structural-related cytotoxicity have successfully allowed these peptides to target and cause sufficient damage to malignant cells with minimal cytotoxicity effects towards healthy cells. On top of that, some these pure peptides had adopted multiple anticancer mechanisms and demonstrated collective anticancer effects within a single application. CONCLUSION: Our review exclusively selected peptides and toxins found identified from various natural sources in combating malignant cells, their selectivity towards specific anticancer mechanisms, and the prospective of conjugated peptide as a single entity for a new therapeutic strategy.

Extensive Allelic Diversity of MHC Class I in Wild Mallard Ducks.

MHC class I is critically involved in defense against viruses, and diversity from polygeny and polymorphism contributes to the breadth of the immune response and health of the population. In this article, we examine MHC class I diversity in wild mallard ducks, the natural host and reservoir of influenza A viruses. We previously showed domestic ducks predominantly use UAA, one of five MHC class I genes, but whether biased expression is also true for wild mallards is unknown. Using RT-PCR from blood, we examined expressed MHC class I alleles from 38 wild mallards (Anas platyrhynchos) and identified 61 unique alleles, typically 1 or 2 expressed alleles in each individual. To determine whether expressed alleles correspond to UAA adjacent to TAP2 as in domestic ducks, we cloned and sequenced genomic UAA-TAP2 fragments from all mallards, which matched transcripts recovered and allowed us to assign most alleles as UAA Allelic differences are primarily located in α1 and α2 domains in the residues known to interact with peptide in mammalian MHC class I, suggesting the diversity is functional. Most UAA alleles have unique residues in the cleft predicting distinct specificity; however, six alleles have an unusual conserved cleft with two cysteine residues. Residues that influence peptide-loading properties and tapasin involvement in chicken are fixed in duck alleles and suggest tapasin independence. Biased expression of one MHC class I gene may make viral escape within an individual easy, but high diversity in the population places continual pressure on the virus in the reservoir species.

Crude Ethanol Extract of Pithecellobium ellipticum as a Potential Lipid-Lowering Treatment for Hypercholesterolaemia.

If left untreated, hypercholesterolaemia can lead to atherosclerosis, given time. Plants from the Fabaceae family have shown the ability to significantly suppress atherosclerosis progression. We selected four extracts from Pithecellobium ellipticum, from the Fabaceae family, to be screened in a 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) assay. The ethanol extract, at a concentration of 500 µ g/mL, exhibited superior inhibition properties over the other extracts by demonstrating 80.9% inhibition, while 0.223 µ g/mL of pravastatin (control) showed 78.1% inhibition towards enzymatic activity. These findings led to the fractionation of the ethanol extract using ethyl acetate : methanol (95 : 5), gradually increasing polarity and produced seven fractions (1A to 7A). Fraction 7A at 150 µ g/mL emerged as being the most promising bioactive fraction with 78.7% inhibition. FRAP, beta carotene, and DPPH assays supported the findings from the ethanol extract as it exhibited good overall antioxidant activity. The antioxidant properties have been said to reduce free radicals that are able to oxidize lipoproteins which are the cause of atherosclerosis. Phytochemical screenings revealed the presence of terpenoid, steroid, flavonoid, and phenolic compounds as the responsible group of compound(s), working individually or synergistically, within the extract to prevent binding of HMG-CoA to HMG-CoA reductase.