Comparing the wound healing potential of natural rubber latex serum and F1-protein: An in vivo approach.

Chronic wounds pose significant health concerns. Current treatment options include natural compounds like natural rubber latex (NRL) from Hevea brasiliensis. NRL, particularly the F1 protein fraction, has demonstrated bioactivity, biocompatibility, and angiogenic effects. So far, there is no study comparing F1 protein with total NRL serum, and the necessity of downstream processing remains unknown. Here, we evaluated the angiogenic potential of F1 protein compared to total NRL serum and the need for downstream processing. For that, ion exchange chromatography (DEAE-Sepharose), antioxidant activity, physicochemical characterization, cell culture in McCoy fibroblasts, and wound healing in Balb-C mice were performed. Also, the evaluation of histology and collagen content and the levels of inflammatory mediators were quantified. McCoy fibroblast cell assay showed that F1 protein (0.01 %) and total NRL serum (0.01 %) significantly increased cell proliferation by 47.1 ± 11.3 % and 25.5 ± 2.5 %, respectively. However, the AA of F1 protein (78.9 ± 0.8 %) did not show a significant difference compared to NRL serum (77.0 ± 1.1 %). F1 protein and NRL serum were more effective in wound management in rodents. Histopathological analysis confirmed accelerated healing and advanced tissue repair. Similarly, the F1 protein (0.01 %) increased collagen, showing that this fraction can stimulate the synthesis of collagen by fibroblastic cells. Regarding cytokines production (IL-10, TNF-α, IFN-γ), F1 protein and NRL serum did not exert an impact on the synthesis of these cytokines. Furthermore, we did not observe statistically significant changes in dosages of enzymes (MPO and EPO) among the groups. Nevertheless, Nitric Oxide dosage was reduced drastically when the F1 protein (0.01 %) protein was applied topically. These findings contribute to the understanding of F1 protein and NRL serum properties and provide insights into cost-effectiveness and practical applications in medicine and biotechnology. Therefore, further research is needed to assess the economic feasibility of downstream processing for NRL-based herbal medicine derived from Hevea brasiliensis.

CEA-delta could be a biomarker of tumor phenotype, clinical stage, and chemotherapeutic response in rectal cancer with OCT4-positive cancer stem cells.

Background: There is very limited evidence on biomarkers for evaluating the clinical behavior and therapeutic response in rectal cancer (RC) with positive expression of cancer stem cells (CSCs). Methods: An exploratory prospective study was conducted, which included fresh samples of tumor tissue from 109 patients diagnosed with primary RC. Sociodemographic, pathological and clinical characteristics were collected from medical records and survey. The OCT4 protein was isolated using the Western Blot technique. It was calculated the ΔCEA, ΔOCT4, and ΔOCT4/GUSB values by assessing the changes before and after chemotherapy, aiming to evaluate the therapeutic response. Results: Patients had an average age of 69.9 years, with 55% (n=60) being male. Approximately 63.3% of the tumors were undifferentiated, and the most frequent staging classification was pathological stage III (n=64; 58.7%). Initial positive expression was observed in 77.1% of the patients (n=84), and the median ΔCEA was -1.03 (-3.82 - 0.84) ng/ml, with elevated levels (< -0.94 ng/ml) found in 51.4% of the subjects (n=56). Being OCT4 positive and having an elevated ΔCEA value were significantly associated with undifferentiated tumor phenotype (p=0.002), advanced tumor progression stage (p <0.001), and negative values of ΔOCT4 (p <0.001) (suggestive of poor therapeutic response) compared to those without this status. Conclusion: This study identified a significant and directly proportional association among the values of ΔCEA, ΔOCT4, and ΔOCT4/GUSB. These findings suggest that ΔCEA holds potential as a clinical biomarker for determining the undifferentiated tumor phenotype, advanced clinical stage, and poor therapeutic response in RC with CSCs positive expression.

Effects of Low-Level Laser Therapy and Purified Natural Latex (Hevea brasiliensis) Protein on Injured Sciatic Nerve in Rodents: Morpho-Functional Analysis.

The present study analyzed the effects of low-level laser therapy (LLLT) and the purified natural latex protein (Hevea brasiliensis, F1 protein) on the morpho-function of sciatic nerve crush injuries in rats. One-hundred and eight male Wistar rats were randomly allocated to six groups (n = 18): 1. Control; 2. Exposed (nerve exposed); 3. Injury (injured nerve without treatment); 4. LLLT (injured nerve irradiated with LLLT (15 J/cm2, 780 nm)); 5. F1 (injured nerve treated with F1 protein (0.1%)); and 6. LLLT + F1 (injured nerve treated with LLLT and F1). On the 1st, 7th, 14th, and 56th days after injury, a functional sensory analysis of mechanical allodynia and mechanical hyperalgesia and a motor analysis of grip strength and gait were performed. After 3, 15, and 57 days, the animals were euthanized for morphometric/ultrastructural analyses. The treatments applied revealed improvements in morphometric/ultrastructural parameters compared to the injured group. Sensory analyses suggested that the improvements observed were associated with time progression and not influenced by the treatments. Motor analyses revealed significant improvements in grip strength from the 7th day in the LLLT group and in gait from the 56th day in all treated groups. We concluded that even though the morphological analyses showed improvements with the treatments, they did not influence sensory recovery, and LLLT improved motor recovery.

Prognostic Significance of ALDH1, Bmi1, and OCT4 Expression in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma.

BACKGROUND: Increasing evidence suggests the involvement of cancer stem cells (CSCs) in both oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC). Among the various CSC markers, aldehyde dehydrogenase (ALDH) 1, B cell-specific Moloney murine leukaemia virus integration site 1 (Bmi1), and octamer-binding protein 4 (OCT4) have been noted to increase in OSCC. The aim of the study was to analyze ALDH1, Bmi1, and OCT4 expression in OED and OSCC with clinicopathologic correlation and survival analysis. METHODS: A total of 40 cases each of OED and OSCC were retrieved from departmental archives. Expression of ALDH1, Bmi1, and OCT4 was analyzed using immunohistochemistry and was correlated with clinicopathological parameters. A follow-up ranging from 6 to 52 months was considered for Kaplan-Meier survival analysis. The log-rank test was performed to analyze significant difference in survival rates. RESULTS: The expression levels of ALDH1, Bmi1, and OCT4 increased significantly from OED through OSCC (P < .05). The expression of ALDH1 and OCT4 showed a significant correlation with lymph node metastasis. Positive cases of ALDH1 showed a significantly reduced survival rate compared to cases showing negative expression. Kaplan-Meier survival analysis showed a significant reduction of survival rate (P = .00) in patients showing a positive expression for all the 3 markers. CONCLUSION: ALDH1 and OCT4 could be used as individual prognostic markers for assessing prognosis. ALDH1, Bmi1, and OCT4 could be used as a collective panel of markers to enable surgeons in predicting the prognosis of patients and thereby carry out prompt follow-up for such cases.

Efficacies of immunotherapy with polypeptide vaccine from ProDer f 1 in asthmatic mice.

Allergic asthma is associated with the major house dust mite group 1 allergens Der p 1 and Der f 1, which belongs to the papin-like protease family and is the most potent of indoor allergens and allergen-specific immunotherapy (SIT), is seen as effective intervention for the entity. The current study was designed to verify the SIT efficacies of the enzymatic hydrolysates (papain and trypsin) in mice with asthma. We initially developed the asthmatic mouse models with ProDer f 1, and respectively applied recombinant ProDer f 1 protein and the two kinds of enzymatic hydrolysates for SIT. The results were verified by measuring the contents of IL-4, IL-10, IL-17 and IFN-γ changed in both bronchoalveolar lavage fluid (BALF) and supernatant of splenocyte culture as well as level changes of specific IgE and IgG2a in the serum. After SIT intervention, the symptoms of allergic inflammation was alleviated significantly in mice treated with ProDer f 1 protein and the two enzymatic hydrolysates via detection of the lung tissue sections, and infiltration of inflammatory cells was also notably depressed as compared with the models, though the epithelial structure in airways remained similar with the PBS group. In addition, we observed lower serum contents of the specific IgE antibody and lower levels of IL-4, IL-17 in BALF and splenic cells in mice undergone SIT, whereas specific IgG2a, IFN-γ and IL-10 in BALF and supernatant of splenocyte culture were higher as compared to the asthma group. The findings suggest the SIT using the above two kinds of hydrolysates may effectively inhibit the allergic inflammation in the airways of mouse models sensitized with ProDer f 1 protein.

A High Thymidylate Synthase Expression is Related to Better Outcome for Advanced Gastric Cancer Patients Treated with 5-FU Chemotherapy after Curative Resection

BACKGROUND: The expressions of thymidylate synthase (TS), E2F-1, pRb, and p53 are correlated with DNA synthesis. The significance of their expressions is still controversial for predicting the outcome of 5-fluorouracil (5-FU) therapy in the patients with advanced gastric carcinoma. Furthermore, their prognostic value in the metastatic lesions of gastric carcinoma has not yet been confirmed. METHODS: To ascertain their prognostic value, we immunohistochemically analyzed the expressions of TS, E2F-1, pRb, and p53 in the primary tumors and the related metastatic lymph nodes, and we then compared the survival between the high and low expression group of each protein. Ninety four patients with advanced gastric carcinoma who were treated by complete resection and adjuvant 5-FU chemotherapy were analyzed. RESULTS: The TS expression in primary tumors was significantly correlated with that of E2F-1. The expression of these genes showed no significant difference between the primary tumors and the metastatic lymph nodes except for E2F-1, which was significantly higher in the lymph node metastasis than in the primary tumors. After complete resection and 5-FU-based adjuvant chemotherapy, patients with a high TS expression in the primary tumors showed a longer survival than those patients having primary tumors with a low TS expression (p=0.0392). CONCLUSION: A high TS expression in the primary tumors may be related to a better outcome for advanced gastric cancer patients who were treated with 5-FU chemotherapy after curative resection.