Capsaicin Encapsulated Chitosan Nanoparticles Augments Anticarcinogenic and Antiproliferative Competency Against 7,12 Dimethylbenz(a)anthracene Induced Experimental Rat Mammary Carcinogenesis

Background: Capsaicin is a powerful phytochemical spotted in chilies, starkly tied up with a bunch of health benefits but its clinical applications in cancer therapy are limited due to its poor solubility, and low bioavailability. Nanotechnology offers a strategy to discover new formulations for hydrophobic agent. Aim: The main intent of the current research was to investigate the effect of Capsaicin encapsulated chitosan nanoparticles (CAP@CS-NP) on 7,12-Dimethylbenz(a)anthracene (DMBA) induced mammary carcinogenesis in rats. Methodology: Mammary tumor was induced in female rats by injecting DMBA (25mg/kg b.wt) at the first week of the experiment. After 7 weeks, CAP@CS-NP (4mg/kg b.wt) was administered orally to DMBA induced tumor bearing rats for 21 days (thrice per week). The experiment was terminated at the end of the 14th week and their plasma and tissue sections were analyzed. Results: We found that significantly elevated levels of lipid peroxidation and diminished levels of antioxidant status in plasma, liver and mammary tissues. Increased levels of detoxification phase I enzymes and dropped levels of phase II enzymes in liver and mammary tissues in DMBA induced tumor bearing rats. As a result, oral administration of CAP@CS-NP suppressed the tumor growth, significantly raised body weight and restored abnormal enzymatic levels to near normal ranges. Additionally, histopathological and immunohistochemical analysis were also confirmed that CAP@CS-NP protects DMBA mediated cellular disruption and also inhibits abnormal cell proliferation. Conclusion: These findings suggest that nano encapsulation of CAP@CS-NP could be useful in targeted drug delivery and act as a promising chemotherapeutic agent to treat mammary carcinogenesis.

The Emerging Landscapes of Long Noncoding RNA in Thyroid Carcinoma: Biological Functions and Clinical Significance

Thyroid carcinoma (TC) is one of the most prevalent primary endocrine tumors, and its incidence is steadily and gradually increasing worldwide. Accumulating evidence has revealed the critical functions of long noncoding RNAs (lncRNAs) in the tumorigenesis and development of TC. Many TC-associated lncRNAs have been documented to be implicated in TC malignant behaviors, including abnormal cell proliferation, enhanced stem cell properties and aggressiveness, and resistance to therapeutics, through interaction with proteins, DNA, or RNA or encoding small peptides. Therefore, further elucidating the lncRNA dysregulation sheds additional insights into TC tumorigenesis and progression and opens new avenues for the early diagnosis and clinical therapy of TC. In this review, we summarize the abnormal expression of lncRNA in TC and the fundamental characteristics in TC tumorigenesis and development. Additionally, we introduce the potential prognostic and therapeutic significance of lncRNAs in TC.

Transcription Factors and Methylation Drive Prognostic miRNA Dysregulation in Hepatocellular Carcinoma

Many dysregulated microRNAs (miRNAs) have been suggested to serve as oncogenes or tumor suppressors to act as diagnostic and prognostic factors for HCC patients. However, the dysregulated mechanisms of miRNAs in HCC remain largely unknown. Herein, we firstly identify 114 disordered mature miRNAs in HCC, 93 of them are caused by dysregulated transcription factors, and 10 of them are driven by the DNA methylation of their promoter regions. Secondly, we find that seven up-regulated miRNAs (miR-9-5p, miR-452-5p, miR-452-3p, miR-1180-3p, miR-4746-5p, miR-3677-3 and miR-4661-5p) can promote tumorigenesis via inhibiting multiple tumor suppressor genes participated in metabolism, which may act as oncogenes, and seven down-regulated miRNAs (miR-99-5p, miR-5589-5p, miR-5589-3p, miR-139-5p, miR-139-3p, miR-101-3p and miR-125b-5p) can suppress abnormal cell proliferation via suppressing a number of oncogenes involved in cancer-related pathways, which may serve as tumor suppressors. Thirdly, our findings reveal a mechanism that transcription factor and miRNA interplay can form various regulatory loops to synergistically control the occurrence and development of HCC. Finally, our results demonstrate that this key transcription factor FOXO1 can activate a certain number of tumor suppressor miRNAs to improve the survival of HCC patients, suggesting FOXO1 as an effective therapeutic target for HCC patients. Overall, our study not only reveals the dysregulated mechanisms of miRNAs in HCC, but provides several novel prognostic biomarkers and potential therapeutic targets for HCC patients.

PPAR-α Modulators as Current and Potential Cancer Treatments

Cancer is one of the leading causes of mortality worldwide. PPAR modulators may hold great potential for the management of cancer patients. Indeed, PPARs are critical sensors and regulators of lipid, and they are able to promote eNOS activation, regulate immunity and inflammation response, and affect proliferation and differentiation of cancer cells. Cancer, a name given to a group of diseases, is characterized by multiple distinctive biological behaviors, including angiogenesis, abnormal cell proliferation, aerobic glycolysis, inflammation, etc. In the last decade, emerging evidence has shown that PPAR-α, a nuclear hormone receptor, can modulate carcinogenesis via exerting effects on one or several characteristic pathological behaviors of cancer. Therefore, the multi-functional PPAR modulators have substantial promise in various types of cancer therapies. This review aims to consolidate the functions of PPAR-α, as well as discuss the current and potential applications of PPAR-α agonists and antagonists in tackling cancer.

refMiR 142 5p inhibits cell invasion and migration by targeting DNMT1 in breast cancer

Abnormal cell proliferation caused by abnormal transcription regulation mechanismseems to be one of the reasons for the progression of breast cancer and also thepathological basis. MicroRNA 142 5p (miR 142 5p) is a low expressed miRNA inbreast cancer. T he role of MKL1's regulation of DNMT1 in breast cancer cellproliferation and migration is still unclear. MKL 1 (myocardi n related transcriptionfactor A) can bind to the conserved cis regulatory element CC (A/T) 6GG (called CarGbox) in the promoter to re gulate the transcription of miR 142 5p. The expression ofmiR 142 5p and MKL 1 are positively correlated. In addition, it has been proved thatDNMT1 is the target of miR 142 5p, which inhibits the expression of DNMT1 bytargeting the 3'UTR of DNMT1, thereby forming a feedback loop and inhibiting themigration and proliferation of breast cancer. Our data provide important and novelinsights into the MKL 1/miR 142 5p/DNMT1/maspin signaling pathway, and maybecome a new idea for breast cancer diagnosis, treatment and prognosis.

Alkaloids of Peganum harmala; anticancer biomarkers with promising outcomes

Background: Cancer is a serious and growing global health issue worldwide. In the cancerous cells, the normal cell cycle has been disrupted via the series of irreversible changes. Recently, the investigations on herbal medicine and clarifying the phytochemicals potential in treat cancer has been increased. The combination of phytochemicals with conventional approaches in cancer treatment can improve outcomes via advancing cell death, restraining cell proliferation and invasion, sensitizing cancerous cells, and promoting the immune system. Therefore, phytochemicals can be introduced as relevant complementary medicaments in cancer therapy. Peganum harmala L. (Zygophyllaceae) as a valuable medicinal herb, possesses various alkaloid ingredient. Objective: Pointing to the importance of new avenues for cancer management and of P. harmala convincing effect in this field, this review strived to collect a frame to epitome possible scopes for the development of novel medicines in cancer treatment. Methods: Keywords "Peganum harmala" and cancer, or chemotherapy, or anti-neoplasm were searched through the "Scopus", database up to the 29th of February 2020. Papers linking to agriculture, chemistry, environmental, and genetics sciences were omitted and, papers centered on cancer were selected. Result and Discussion: In the current study, 42 related papers to cancer treatment and 22 papers on alkaloid bioactive components are collected from 72 papers. The β-carboline alkaloids derived from P. harmala, especially harmine, demonstrate notable anticancer properties by targeting apoptosis, autophagy, abnormal cell proliferation, angiogenesis, metastasis, and cytotoxicity. Based on the collected information, P. harmala holds significant anticancer activity. Considering the mechanism of the various anticancer drugs and their acting similarity to P. harmala, the alkaloids derived from this herb, particularly harmine, can introduce as a novel anticancer medicine solely or in adjuvant cancer therapy.

Anti-Migratory Effects of 4′-Geranyloxyferulic Acid on LPS-Stimulated U937 and HCT116 Cells via MMP-9 Down-Regulation: Involvement of ROS/ERK Signaling Pathway

Matrix metalloproteinases (MMPs) play a crucial role in tumor angiogenesis, and metastasis. 4′-geranyloxyferulic acid (GOFA) has anti-tumor and anti-inflammatory proprieties. Herein, we aimed to determine whether this compound affects cell survival, invasion, and migration through reactive oxygen species (ROS)-mediated MMPs activation of extracellular signal-regulated kinases (ERKs) and p38 signaling in lymphocytic histiocytoma (U937) and colorectal cancer (HCT116) cells. We observed that lipopolysaccharide (LPS) stimulated U937 and HCT116 cells presented abnormal cell proliferation and increased metalloproteinase (MMP-9) activity and expression. Non-cytotoxic doses of GOFA blunted matrix invasive potential by reducing LPS-induced MMP-9 expression and cell migration via inhibiting ROS/ ERK pathway. GOFA also attenuated apoptosis and cell senescence. Our findings indicate that GOFA, inhibiting cancer cell proliferation and migration, could be therapeutically beneficial to prevent tumor metastasis.

Combination laser therapy for epiretinal membrane: a physico-mathematical model

An epiretinal membrane (ERM) is a product of abnormal cell proliferation on the inner surface of the retina and at the vitreomacular interface. Laser therapy is an interesting modality for treating pathologies of the vitreomacular interface. The wise choice of laser settings (wavelength, exposure time, power) minimizes damage to the retina and ensures a good therapeutic effect. This could be a serious impetus to the development and refinement of laser technologies for treating ERM. This work investigates the biophysical response of structural retinal components, including the dynamics of temperatures and acoustic oscillations, protein denaturation, and stimulation of tissue regeneration, to a quasi-cw laser beam and a subsequent series of laser micropulses. The manuscript also analyzes the mechanisms underlying the therapeutic effect of the proposed laser therapy in patients with ERM.

Proteomics in Psoriasis

Psoriasis has been thought to be driven primarily by innate and adaptive immune systems that can be modified by genetic and environmental factors. Complex interplay between inflammatory cytokines and T-cells, especially Th1 and Th17 cells, leads to abnormal cell proliferation and psoriatic skin lesions. Nevertheless, such mechanisms do not entirely represent the pathogenesis of psoriasis. Moreover, earlier and better biomarkers in diagnostics, prognostics, and monitoring therapeutic outcomes of psoriasis are still needed. During the last two decades, proteomics (a systematic analysis of proteins for their identities, quantities, and functions) has been widely employed to psoriatic research. This review summarizes and discusses all of the previous studies that applied various modalities of proteomics technologies to psoriatic skin disease. The data obtained from such studies have led to (i) novel mechanisms and new hypotheses of the disease pathogenesis; (ii) biomarker discovery for diagnostics and prognostics; and (iii) proteome profiling for monitoring treatment efficacy and drug-induced toxicities.