The Influence of Cellulosic Polymer's Variables on Dissolution/Solubility of Amorphous Felodipine and Crystallization Inhibition from a Supersaturated State.

The collective impact of cellulosic polymers on the dissolution, solubility, and crystallization inhibition of amorphous active pharmaceutical ingredients (APIs) is still far from being adequately understood. The goal of this research was to explore the influence of cellulosic polymers and incubation conditions on enhancement of solubility and dissolution of amorphous felodipine, while inhibiting crystallization of the drug from a supersaturated state. Variables, including cellulosic polymer type, amount, ionic strength, and viscosity, were evaluated for effects on API dissolution/solubility and crystallization processes. Water-soluble cellulosic polymers, including HPMC E15, HPMC E5, HPMC K100-LV, L-HPC, and MC, were studied. All cellulosic polymers could extend API dissolution and solubility to various extents by delaying crystallization and prolonging supersaturation duration, with their effectiveness ranked from greatest to least as HPMC E15 > HPMC E5 > HPMC K100-LV > L-HPC > MC. Decreased polymer amount, lower ionic strength, or higher polymer viscosity tended to decrease dissolution/solubility and promote crystal growth to accelerate crystallization. HPMC E15 achieved greatest extended API dissolution and maintenance of supersaturation from a supersaturated state; this polymer thus had the greatest potential for maintaining sustainable API absorption within biologically relevant time frames.

Identification of the collagen family as prognostic biomarkers in papillary thyroid carcinoma.

OBJECTIVE: The aim of this study was to construct a collagen-related prognostic model for thyroid cancer and to investigate prognostic value of collagen family genes for thyroid cancer. METHODS: A LASSO Cox regression model for thyroid cancer was developed based on the expression profiles of collagen-related genes. Kaplan-Meier survival analysis was performed for high and low risk groups. The ROC method was used to assess its predictive performance. Predictive independence was verified by multivariate Cox regression analysis. The relationship between this feature and immune cell infiltration was analyzed by tumor microenvironment. COL18A1 was validated by immunohistochemistry and RT-PCR in thyroid cancer tissues. The effect of COL18A1 on cell proliferation, migration and invasion ability of tumor cells were further valuated by CCK-8 assay and transwell assay. The effect of COL18A1 on the immune escape ability of tumor cells was further valuated by cytotoxicity assays. RESULTS: A model including 4 collagen family genes was developed to predict thyroid cancer prognosis. Patients with high-risk score had a poorer prognosis than those with low-risk scores for 1-, 2-, 3-, and 5- year survival. The model independently predicted prognosis after adjusting for other prognostic factors. A nomogram combining risk score and age was constructed with high sensitivity and specificity. This feature was significantly associated with immune cell infiltration. COL18A1 was aberrantly over-expressed in thyroid cancer compared with control tissues and significantly increased proliferative capacity, migration capacity, invasion capacity, and immune escape ability of tumor cells. CONCLUSION: Our findings establish a signature associated with collagen family genes that can be a promising tool to predict the prognosis of thyroid cancer. High COL18A1 expression significantly correlates with the poor prognosis of patients and enhances the immune escape ability of tumor cells.

[Electroacupuncture at "Zusanli"(ST36) and "Xuanzhong"(GB39) improves inflammatory reactions and reduces levels of serum MMP-3 and MMP-9 in adjuvant arthritis rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Zusanli" (ST36) and "Xuanzhong" (GB39) on joint inflammatory reactions and serum matrix metalloproteinase-3 (MMP-3) and MMP-9 contents in rats with adjuvant arthritis (AA), so as to explore its mechanism underlying improvement of AA. METHODS: Forty male SD rats were randomly divided into control, model, acupoint and non-acupoint groups (n=10 in each group). The arthritis model was established by hypodermic injection of complete Freund's adjuvant (0.1 mL) into the bilateral footpads. EA (2 Hz, 3 V) was applied to bilateral ST36 and GB39 or two non-acupoints (5 mm left to ST36 and GB39) for 15 min, once every other day for a total of 8 times. The arthritis index score was evaluated according to the severity of local erythema and swelling of the ankle joint, plantar joint, toe joint and foot metacarpal joint (0-4 points). The inflammatory conditions of the ankle joint were observed by H.E. staining, and the contents of serum MMP-3 and MMP-9 were assayed by ELISA. RESULTS: The arthritis index score and serum concentrations of MMP-3 and MMP-9 were significantly increased in the model group relevant to the control group (P<0.01), and obviously decreased after EA intervention on the 18th day (P<0.01). The therapeutic effect of acupoint EA was notably superior to non-acupoint EA in down-regulating the arthritis index score and serum MMP-3 and MMP-9 concentrations (P<0.01). Under light microscope, marked proliferation of the synovial cells, inflammatory cell infiltration and increase of newly blood vessels were observed in the ankle joint of the model group, which was relatively milder in the acupoint group. CONCLUSION: acupoint EA intervention can significantly alleviate the inflammatory reaction of AA rats, which may be related to its effects in reducing the levels of serum MMP-3 and MMP-9.