Antitumor Activity of Ferulic Acid Against Ehrlich Solid Carcinoma in Rats via Affecting Hypoxia, Oxidative Stress and Cell Proliferation.

Background Ferulic acid is a natural compound commonly found in fruits and vegetables like tomatoes, sweet corn, rice bran, and dong quai. It has various beneficial effects on the body, such as anti-inflammatory, anti-apoptotic, hepatoprotective, cardioprotective, and neuroprotective properties. Aims We conducted a study to investigate the antitumor activity of ferulic acid against Ehrlich solid carcinoma (ESC), specifically by affecting hypoxia-inducible factor (HIF)-1α and its subsequent effects on other factors like nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), cellular Myc (cMyc), cyclin D1, mammalian target of rapamycin (mTOR), and signal transducer and activator of transcription 3 (STAT3). Materials and methods The study involved implanting rats with ESC cells and administering 50 mg/kg of ferulic acid orally daily for eight days. Sections of the muscles with ESC were stained with toluidine blue or immunostained with anti-HIF-1α antibodies. The tumor samples were used to evaluate the expression of HIF-1α, Nrf2, HO-1, cMyc, cyclin D1, mTOR, and STAT3. Results Ferulic acid increased mean survival time, reduced tumor volume and weight, and improved the appearance of the tumor tissue. Furthermore, ferulic acid significantly elevated the expression of Nrf2 and HO-1, while reducing the expression of HIF-1α, Nrf2, HO-1, cMyc, cyclin D1, mTOR, and STAT3. Conclusions Ferulic acid can reduce tumor size and weight while improving the structure of muscle cells, suggesting it may have antineoplastic activity against ESC. Further investigation revealed that ferulic acid downregulates HIF-1α, increasing the expression of antioxidant proteins Nrf2 and HO-1. Additionally, ferulic acid decreases the expression of proliferation markers cMyc and cyclin D1 and downregulates cellular regulators mTOR and STAT3.

Metal-Organic Frameworks for Diabetic Wound Healing.

Wound healing is one of the most important issues in clinical and scientific research. The healing process is complex and requires many agents to overcome in a short duration. A recent class of porous materials called metal-organic frameworks (MOFs) has great potential towards improving wound healing. This is attributed to their well-designed structures with large surface areas amenable to cargo loading and adjustable pore size ready for biological implementations. MOFs are assembled by several metal centers and organic linkers. In particular, metal ions can be released from MOFs when they are degraded in the biological environment. This endows MOF-based systems with dual functions to typically shorten the healing duration. This work focuses on using MOFs with different metal centers such as copper (Cu), zinc (Zn), cobalt (Co), magnesium (Mg), and zirconium (Zr) for healing diabetic wounds as one of the most required clinical issues to be resolved. By figuring out the presented examples of this work, several potential research ideas can emerge to explore new porous materials or even new MOFs for more control over the healing process.

Vitamin D status, vitamin D receptor gene polymorphism, and haplotype in patients with cutaneous leishmaniasis: Correlation with susceptibility and parasite load index.

BACKGROUND: CL endemicity was reported worldwide including in Saudi Arabia, imposing a major challenge on the health authorities. Vitamin D and its receptor (VDR) are key modulators of the immune response where the VDR is expressed. A remarkable lack of data exists in humans about the contribution of vitamin D and polymorphisms of the VDR gene in protozoan infections, especially cutaneous leishmaniasis (CL). OBJECTIVE: This is the first work conducted to assess the relationship between vitamin D status, polymorphisms of the VDR gene (BsmI, ApaI, TaqI, and FokI), and VDR haplotype with parasite tissue load and susceptibility to CL. METHODS: Fifty-two patients with confirmed CL (21 patients receiving vitamin D medication and 31 patients not receiving it) and 46 control subjects participated in this cross-sectional investigation. VDR genotyping was determined by restriction fragment length polymorphism analysis. Serum levels of 25-OH vitamin D were assessed using the ELISA method in all participants. The skin biopsy quantified the parasite load based on the Ridley parasitic index. RESULTS: The mean serum level of 25-OH vitamin D in CL patients who were not receiving vitamin D therapy was significantly lower compared to CL patients on vitamin D therapy and controls (p <0.001 for both) and CL patients with no history of vitamin D therapy had a significantly higher frequency of vitamin D deficiency compared to CL patients on vitamin D therapy and controls (p < 0.05). Compared to CL patients with no history of vitamin D therapy, CL patients receiving vitamin D therapy had a significantly lower mean size of the lesion and RPI (p = 0.02, .03 respectively). The frequency of genotype "aa" and its "a" allele in ApaI SNP of VDR was significantly lower in CL patients compared to controls (p = 0.006 and 0.03 respectively). However, patients with CL had a considerably greater frequency of the "A" allele than the controls (p = 0.03), suggesting its role in CL susceptibility. There was no statistically significant difference between the two groups in the genotype and allele frequency distributions of BsmI, TaqI, and FokI (p > 0.05). When compared to controls, CL cases had a considerably greater frequency of the "B-A-T-F" haplotype (p = 0.04), and a significantly lower frequency of the "B-a-T-F" haplotype (p = 0.01) suggesting that these haplotypes may have the potential susceptibility or protection against CL respectively. The "Aa" genotype in ApaI SNP of VDR had considerably lower levels of vitamin D with higher parasite load compared to the "AA" and: aa" genotypes (p = 0.02,0.02 respectively). A significant negative correlation was found between the parasite load and 25-OH vitamin D levels (r2 = -0.53, p< 0.001). CONCLUSIONS: According to these findings, vitamin D levels and "ApaI" VDR gene polymorphisms could affect the parasite load and susceptibility to infection, whereas BsmI, FokI, and TaqI polymorphisms did not. Correction of vitamin D levels may aid in CL management.

Solitary Angiokeratoma in a Young Man: A Rare Case Report.

Angiokeratoma is a rare vascular cutaneous disorder that usually presents as mostly asymptomatic aside from multiple dark red to blue or black papules over the skin in several clinically distinct conditions. Very rarely, it occurs in solitary localized forms that clinically mimic vascular disorders or sometimes melanoma. Solitary cutaneous angiokeratoma may result from damage to a venule's wall in the papillary dermis. This case study describes a 28-year-old male with a single angiokeratoma on the lateral aspect of his upper thigh and a clinical suspicion of a cutaneous melanocytic tumor. This case is intended to raise awareness about such rare skin lesions and the importance of histopathological examination.

Sun-Exposed versus Sun-Protected Cutaneous Basal Cell Carcinoma: Clinico-Pathological Profile and p16 Immunostaining.

INTRODUCTION: Although widespread, BCC is still relatively poorly understood in regards to pathogenesis and prognosis, particularly the lesions formed on anatomical sites away from sun exposure. With the aim of deepening our understanding of the pathogenesis and clinico-pathological correlations of BCCs, we conducted this study. METHODS: Tissue blocks and data of 52 Egyptian patients diagnosed with BCC were retrieved for clinical information and inclusion criteria, then re-examined histologically; p16 immunostaining was carried out and evaluated for analysis and comparison between the two groups, i.e., sun-exposed and sun-protected. RESULTS: Sex, age, clinical suspicion, tumor size, recurrence status, and histologic variants did not show a significant difference between the sun-protected and sun-exposed groups; however, the mean ages recorded were 67.2 vs. 62.7 for the sun-protected and sun-exposed groups, respectively. A total of 52% of BCCs were positive for p16. The sun-protected lesions showed p16 positivity in 61% of cases, whereas 49% of the sun-exposed lesions were positive with no significant difference. There was a significant difference in p16 expression between the recurrent and non-recurrent lesions. CONCLUSIONS: A significant difference was seen in the case of cancer recurrence, where all the recurrent BCCs in this study demonstrated negative p16 immunostaining of the primary lesions; however, the positively stained cases in total were 52% of BCCs. The mean patient age of the sun-protected group was much higher than in previous peer studies. We assume that the biological, prognostic, and clinical aspects of p16 protein expression in BCCs are still far from being clearly understood. Further studies are highly recommended, with more focus on its role in the pathogenesis and the prognostic factors.

"To be or not to Be": Regulatory T cells in melanoma.

In spite of progresses in the therapy of different malignancies, melanoma still remains as one of lethal types of skin tumor. Melanoma is almost easily treatable by surgery alone with higher overall survival rates when it is diagnosed at early stages. However, survival rates are decreased remarkably upon survival if the tumor is progressed to advanced metastatic stages. Immunotherapeutics have been prosperous in the development of anti-tumor responses in patients with melanoma through promotion of the tumor-specific effector T cells in vivo; nonetheless, suitable clinical outcomes have not been satisfactory. One of the underlying causes of the unfavorable clinical outcomes might stem from adverse effects of regulatory T (Treg) cell, which is a prominent mechanism of tumor cells to escape from tumor-specific immune responses. Evidence shows that a poor prognosis and low survival rate in patients with melanoma can be attributed to a higher Treg cell number and function in these subjects. As a result, to promote melanoma-specific anti-tumor responses, depletion of Treg cells appears to be a promising approach; even though the clinical efficacy of different approaches to attain appropriate Treg cell depletion has been inconsistent. Here in this review, the main purpose is to assess the role of Treg cells in the initiation and perpetuation of melanoma and to discuss effective strategies for Treg cell modulation with the aim of melanoma therapy.

Prognosis of patients with hepatocellular carcinoma treated with sorafenib: a comparison of five models in a large Canadian database.

Several systems (tumor-node-metastasis [TNM], Barcelona Clinic Liver Cancer [BCLC], Okuda, Cancer of the Liver Italian Program [CLIP], and albumin-bilirubin grade [ALBI]) were developed to estimate the prognosis of patients with hepatocellular carcinoma (HCC) mostly prior to the prevalent use of sorafenib. We aimed to compare the prognostic and discriminatory power of these models in predicting survival for HCC patients treated with sorafenib and to identify independent prognostic factors for survival in this population. Patients who received sorafenib for the treatment of HCC between 1 January 2008 and 30 June 2015 in the provinces of British Columbia and Alberta, and two large cancer centers in Toronto, Ontario, were included. Survival was assessed using the Kaplan-Meier method. Multivariate Cox regression was used to identify predictors of survival. The models were compared with respect to homogeneity, discriminatory ability, monotonicity of gradients, time-dependent area under the curve, and Akaike information criterion. A total of 681 patients were included. 80% were males, 86% had Child-Pugh class A, and 37% of patients were East Asians. The most common etiology for liver disease was hepatitis B (34%) and C (31%). In all model comparisons, CLIP performed better while BCLC and TNM7 performed less favorably but the differences were small. The utility of each system in allocating patients into different prognostic groups varied, for example, TNM poorly differentiated patients in advanced stages (8.7 months (m) (95% CI 6.5-11.5) versus 8.4 m (95% CI 7.0-9.6) for stages III and IV, respectively) while ALBI had excellent discrimination of early grades (15.6 m [95% CI 13.0-18.4] versus 8.3 m [95% CI 7.0-9.2] for grades 1 and 2, respectively). On multivariate analysis, hepatitis C, alcoholism, and prior hepatic resection were independently prognostic of better survival (P < 0.01). In conclusion, none of the prognostic systems was optimal in predicting survival in sorafenib-treated patients with HCC. Etiology of liver disease should be considered in future models and clinical trial designs.

Exercise treatment for osteoarthritis disability.

Osteoarthritis (OA) is a chronic prevalent condition that affects the synovial joints and can lead to disability. There is no single treatment that is known to cure OA. Most treatments have aimed at reducing symptoms or slowing the progression of the disease and its consequences. Exercise therapy is a common intervention in treating OA, with primary aims of improving functional movement and managing the problems associated with abnormal functional movement. We review the underlying process of exercise treatment and its importance for OA disability. A brief description of OA disease and an OA disability model are introduced, and then the importance of exercise and trends in prescribing exercises for OA are discussed. Finally, future directions and suggestions for research in this field are described.