Latest ArticlesTo investigate the antitumor activity and mechanism of a pyrazole [1,5-a]pyrimidine derivative (BPPA) on human tongue squamous cell carcinoma Cal33 cells.
Cal33 cells were divided into blank group (normal culture), experimental-L, -M, -H groups (1, 2.5 and 5 μmol·L-1BPPA) and combined group [2.5 μmol·L-1BPPA and 5 mmol·L-1 N-acety-L-cysteine (NAC)]. Cell viability was determined by thiazole blue assay. Cell apoptosis was measured using flow cytometry, while apoptosis-related protein expression levels were determined by Western blot analysis. Changes in reactive oxygen species and mitochondrial membrane potential were evaluated using immunofluorescence assay.
The survival rates of Cal33 cells in blank, experimental-L,-M,-H and combined groups were (99.56±0.91)%, (58.31±2.31)%, (47.93±1.67)%, (29.35±4.11)% and (70.27±1.21)%, respectively; cell apoptotic rates were (8.07±1.01)%, (44.04±0.94)%, (49.85±1.75)%, (66.79±0.83)% and (24.33±1.04)%, respectively; the relative fluorescence intensities of reactive oxygen species (ROS) were 1.23±0.21, 3.37±0.35, 15.53±1.46, 20.28±1.24 and 5.59±0.52, respectively; the mitochondrial membrane potential red fluorescence/green fluorescence values were 4.69±0.11, 4.24±0.12, 0.86±0.16, 0.46±0.05 and 2.99±0.11, respectively. Compared with blank group, the above indexes in the experimental-L, -M, -H groups were statistically significant (P<0.01, P<0.001). Compared with experimental-M group, the above indexes in combined group were statistically significant (P<0.01, P<0.001). The relative levels of pro-apoptotic B-cell lymphoma-2 (Bcl-2)-Associated X protein (Bax) in blank, experimental-L,-M,-H groups were 1.00±0.02, 1.94±0.03, 3.73±0.06 and 4.64±0.08, respectively; the relative levels of anti-apoptotic protein Bcl-2 were 1.00±0.02, 0.75±0.04, 0.62±0.02 and 0.46±0.03, respectively. Compared with blank group, the above indexes in the experimental-L, -M, -H groups were statistically significant (P<0.01, P<0.001).
BPPA exhibits anti-head and neck cancer activity by ROS mediating the decrease in mitochondrial membrane potential, thereby inducing apoptosis.
Toll-like receptor 4(TLR4)/ nuclear factor-κB (NF-κB) signaling pathway plays an important role in invasion, proliferation, migration, apoptosis and autophagy of hepatocellular carcinoma cells. Traditional Chinese medicine (TCM) monomers inhibit M2 macrophage polarization, epithelial-mesenchymal transformation (EMT), snail family transcriptional repressor 2 (SLUG) deubiquitination by ubiquitin-specific proteases (USP) and lipopolysaccharide (LPS) -induced cell damage by intervening TLR4/NF-κB signaling pathway. Serum inflammatory chemokine ligand 1(CXCL1) level and cyclooxygenase-2 (COX-2) protein level were significantly decreased and matrixmetalloprotease-9 (MMP-9) protein level was significantly decreased. The expression of MMP-9, decreased the levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF), and interfered with mitochondrial membrane potential (MMP), thereby inhibiting tumor cell invasion and migration, and promoting autophagy and apoptosis of hepatoma cells. The main purpose of this review is to update the latest TCM monomer components that exert anti-liver cancer effect through TLR4/NF-κB signaling, and to clarify the main mechanism of their action on liver cancer, and to provide ideas and methods for exploring more TCM with anti-liver cancer properties, so as to better promote the further development and utilization of TCM resources.
To analyze the effect of insulin degludec/insulin aspart injection combined with metformin extended-release tablets on insulin resistance in patients with type 2 diabetes mellitus (T2DM).
T2DM patients were divided into control group and treatment group using a cohort method. The control group received oral metformin extended-release tablets (0.5 g, tid) and subcutaneous injections of insulin glargine injection (10 U, qd), while the treatment group received oral metformin extended-release tablets (0.5 g, tid) and subcutaneous injections of insulin degludec/insulin aspart injection (0.1-0.2 U·kg-1·d-1, evenly divided before breakfast and dinner). Both groups were treated for 12 weeks. The efficacy, blood glucose control [fasting blood glucose, 2-hour postprandial blood glucose, glycated hemoglobin A1c(HbA1c)], insulin function [fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment-β (HOMA-β)]were compared, and safety was evaluated.
A total of 49 cases were enrolled in the treatment group and 51 cases in the control group. The overall effective rates in the treatment and control groups were 93.88% (46 cases/49 cases) and 80.39% (41 cases/51 cases), respectively, showing a statistically significant difference (P<0.05). After treatment, the fasting blood glucose levels in the treatment and control groups were (5.83±0.79) and (6.53±0.81) mmol·L-1; the 2-hour postprandial blood glucose levels were (7.73±0.86) and (8.41±0.97) mmol·L-1; HbA1c levels were (6.34±0.88)% and (6.80±0.92)%; FINS levels were (6.02±1.13) and (7.13±1.04) mU·L-1; HOMA-IR values were 1.56±0.20 and 2.07±0.23; HOMA-β values were 51.67±3.18 and 47.06±3.31, respectively, with all differences being statistically significant (all P<0.05). The adverse drug reactions in the treatment group mainly included hypoglycemia, nausea, dizziness, and diarrhea, while the adverse drug reactions in the control group mainly included hypoglycemia and nausea. The incidence of adverse drug reactions was 10.20% (5 cases/49 cases) in the treatment group and 11.76% (6 cases /51 cases) in the control group, with no statistically significant difference (P<0.05).
The combination of insulin degludec/insulin aspart injection and metformin extended-release tablets can improve insulin resistance and regulate blood glucose levels in T2DM patients, with good safety profiles.
Doxorubicin is widely used as a first-line therapeutic option in the treatment of several malignant tumors, but its clinical application is severely limited by the dose-dependent and irreversible cardiotoxicity, which has been a long-standing clinical challenge. We analyze the latest clinical guidelines on oncological cardiology and summarize the current status of doxorubicin-induced cardiotoxicity (DIC) prevention and treatment. On this basis, we have gone beyond the traditional view of direct damage to cardiomyocytes, and reviewed the research progress in recent years on the cross-talk between cardiac vascular endothelial cells and cardiomyocytes involved in DIC. The results suggest that cardiac endothelial cells play a key role in the development and maintenance of cardiac function. Doxorubicin not only directly damages these cells, but also disrupts the paracrine signals and physical barriers between them and cardiomyocytes, ultimately leading to an imbalance in cell communication and affecting cardiomyocyte survival and function, resulting in DIC.
Rheumatoid arthritis (RA) is categorized as "bi zheng" and "li-jiebing" in Chinese medicine. Liver and kidney insufficiency, marrow can not nourish the bones, feel the external evil, long-term accumulation in the body, heat into poison, damage to the qi and blood meridians and collaterals, heat and poison, phlegm, blood stasis and paralysis and the onset of the disease, mixed with the real and the imaginary, difficult to be cured. The Notch signaling pathway has a greater relevance to this disease, and it is involved in various pathological processes such as inflammatory cell infiltration, proliferation of fibroblast-like synoviocytes (FLS), microvascular formation and bone destruction. In this paper, the correlation between Notch signaling pathway and this disease is discussed from the perspective of the combination of Chinese and Western medicine, based on the theory of "XU, DU, YU" of traditional Chinese medicine, with the aim of providing a new way of thinking for the research.
To compare the clinical efficacy and safety of sodium bicarbonate ringer’s injection and 0.9% NaCl as resuscitation fluid in the treatment of patients with diabetic ketoacidosis (DKA).
Patients with DKA were randomly divided into treatment group and control group. After enrollment, the treatment group was immediately given sodium bicarbonate ringer’s , and the control group was given 0.9% NaCl for fluid resuscitation. Other treatment protocols for DKA were the same in two groups. The incidence of hyperchloremia in 96 hour the change value of chloride in 96 hours (with the maximum value minus the baseline value), the total volume of fluid administered over 24 hours, the volume of urine produced over 24 hours, and the incidence of acute kidney injury(AKI) were compared between the two groups. Additionally, the incidence of hypokalemia in the two groups during the 96-hour observation period was recorded, and the safety of the intervention was evaluated.
The study cohort comprised 20 cases in the treatment group, of whom two were dislodged, finally 18 cases were included in the statistical analysis. In the control group, 20 cases were enrolled, with one case being dislodged, leaving 19 cases included in the statistical analysis. The incidence of 96 hour hyperchloraemia in the treatment group and the control group was 27.78% (5 cases/18 cases) and 73.68% (14 cases/19 cases), respectively. Furthermore, the change values of chloride in 96 hour were 11.05(9.30, 13.13) and 19.10(14.10, 29.10) mmol·L-1, respectively. Notably, the differences between the two groups were statistically significant(all P<0.05). The total fluid volume was 3 410.00 and 3 600.00 mL, the 24 hour urine output was 2 075.00 and 2 950.00 mL, and the incidence of AKI was 0% (0 cases/18 cases) and 5.26% (1 cases/19 cases) in the treatment group and the control group, respectively. No statistically significant differences were observed in any of the statistical comparisons(all P>0.05). However, the incidence of hypokalaemia in the treatment group(22.22%) was lower than that in the control group(57.89%), and this difference was statistically significant (P<0.05).
The administration of sodium bicarbonate ringer’s injection for the resuscitation of patients with diabetic ketoacidosis has been demonstrated to reduce the incidence of hyperchloremia at 96 hours, and have good safety.
Study on the long non-coding RNA (lncRNA) LINC00922 regulating secreted frizzled related protein 1 (SFRP1) to inhibit the malignant progression of human oral mucosal fibroblasts (hOMF) induced by arecoline.
Cells were divided into blank control (NC) group (hOMF cells were not treated in any way), model group (60 mg·L-1 arecoline treatment), oe-LINC02147 group (60 mg·L-1 arecoline treatment, transfected with overexpression of LINC02147 vector), si-SFRP1 group (60 mg·L-1 arecoline treatment, transfected with overexpression of LINC02147 vector, transfected with SFRP1 inhibitor vector). Real-time fluorescence quantitative polymerase chain reaction was used to detect the relative expression levels of SFRP1 mRNA in each group of cells; immunofluorescence was used to detect the positive expression of alpha-smooth muscle actin (α-SMA) and vimentin in each group of cells; 5-ethynyl-2′-deoxyuridine was used to detect the proliferation rate of each group of cells; dichlorodihydrofluorescein diacetate fluorescence probe method was used to detect the content of reactive oxygen species (ROS) in each group of cells.
The relative expression levels of SERP1 mRNA in model group and oe-LINC02147 group were 1.00±0.08 and 3.75±0.59, respectively; the cell proliferation rates of NC group, model group, oe-LINC02147 group and si-SFRP1 group were (43.61±6.97)%, (12.98±4.27)%, (38.66±5.12)% and (15.73±5.42)%, respectively; ROS content were (9.42±1.73)%, (36.58±6.16)%, (12.89±2.08)% and (33.45±5.76)%, respectively; α-SMA positive expression were 1.00±0.13, 5.02±1.46, 2.36±0.48 and 4.37±0.97, respectively; the positive expressions of vimentin were 1.00±0.15, 4.63±1.51, 1.98±0.85 and 3.92±1.36, respectively. The above indexes in the model group were compared with the NC group, the above indexes in the oe-LINC02147 group were compared with the model group, and the above indexes in the si-SFRP1 group were compared with the oe-LINC02147 group, and the differences were statistically significant (all P<0.001).
LINC02147 may inhibit the malignant progression of arecoline-induced human oral mucosa fibroblasts by regulating SFRP1.
To investigate the effects of baicalein on apoptosis and immune escape of laryngeal carcinoma cells and its mechanism.
Human laryngeal carcinoma TU686 cells were randomly divided into control group(routine culture), baicalein group (50 μmol·L-1 baicalein), Vector group (transfected with Vector+50 μmol·L-1 baicalein) and CD47 group [transfected with differentiation cluster 47(CD47) +50 μmol·L-1 baicalein]. Cell proliferation and apoptosis were detected by 5-acetylidene-2′-deoxyuridine (Edu) method and Annexin V-FITC/PI double staining method. The expression of proliferative and apoptotic proteins were detected by Western blot. Human peripheral lymphocytes were co-cultured with cells in each group to detect the killing rate of TU686 cells. The phagocytosis rate of TU686 cells was observed.
The Edu positive cell rates in control group, baicalein group, Vector group and CD47 group were (36.24±2.74)%, (13.33±1.93)%, (14.22±1.48)% and (27.80±2.74) %, respectively; the apoptosis rates were (3.94±0.40)%, (28.40±1.76)%, (26.60±1.41)% and (12.33±0.84)%, respectively; the relative expressions of CD47 protein were 1.00±0.11, 0.42±0.07, 0.44±0.06 and 1.21±0.12, respectively; the relative expression levels of CyclinD1 protein were 0.86±0.08, 0.37±0.05, 0.36±0.04 and 0.74±0.08, respectively; the relative expression levels of cleaved cysteine aspartate proteinase-7(Cl-Caspase-7) protein were 0.35±0.04, 0.99±0.12, 1.00±0.11 and 0.50±0.06, respectively; the killing rates of human peripheral lymphocytes to TU686 cells (1∶1 ratio) were (10.61±1.19)%, (32.02±2.27)%, (31.86±2.06)% and (14.39±1.07)%, respectively; the phagocytosis rates were (6.35±0.71)%, (11.99±1.64)%, (12.03±0.76)% and (7.06±0.57)%, respectively. The above indicators, baicalein group compared with the control group, Vector group compared with CD47 group, the differences were statistically significant (P<0.05, P<0.01, P<0.001).
Baicalein may induce the apoptosis of laryngeal carcinoma cells and inhibit the immune escape of laryngeal carcinoma cells by inhibiting the expression of CD47, thus slowing down the progression of laryngeal carcinoma.
Saccharomyces boulardii (S. boulardii), as the sole fungal probiotic, exhibits significant therapeutic efficacy in treating various gastrointestinal disorders. In contrast to traditional bacterial probiotic preparations, S. boulardii stands out for its diverse array of biological activities, including anti-inflammatory, antibacterial, enzymatic, metabolic, and anti-toxin properties. S. boulardii is not indigenous to the human microbiome and is resistant to gastric acid, ensuring its stability and tolerability. Clinical research indicates that S. boulardii offers a positive therapeutic effect in treating gastrointestinal disorders such as acute diarrhea, antibiotic-induced diarrhea, inflammatory bowel disease, and irritable bowel syndrome, while also demonstrating high oral safety. Although the specific mechanisms of action of S. boulardii remain unclear, its clinical efficacy has been widely recognized. This article provides an overview of the advancements in S. boulardii’s application in treating childhood gastrointestinal diseases, serving as a reference for future research directions and clinical applications of this fungus.
To explore the effect of honey-processed Hedysari Radix on the metabolism of short-chain fatty acids (SCFAs) in the cecum of rats with spleen qi deficiency.
A total of 48 SPF male SD rats were randomly divided into blank group, model group, control group and experimental group, with 8 rats in each group. The blank group was fed normally, drank water and ate freely for 15 days, and the other groups used the three-factor composite modeling method of bitter cold diarrhea, overwork and hunger and satiety to construct a spleen qi deficiency model rats for 15 days. After the successful replication of the model, the rats in the control group were given 62.5 mg·kg-1 bifidobacterium Lactobacillus triple viable tablets suspension, the experimental group was given 12.6 g·kg-1 honey-processed Hedysari Radix decoction, and the blank group was given the same dose of distilled water, and the model group continued to model for 15 days. Gas chromatography-mass spectrometry (GC-MS) was used to determine the contents of SCFAs in the cecal contents of rats in each group.
The contents of acetic acid, isobutyric acid, butyric acid, isovaleric acid and caproic acid in the cecal contents of rats in the blank group were (3 706.24±401.84), (99.34±39.11), (2 567.95±529.44), (86.50±54.11) and (393.14±103.33) μg·g-1, respectively. Compared with the blank group, the contents of acetic acid, isobutyric acid, butyric acid, isovaleric acid and caproic acid in the cecum contents of spleen-qi deficiency rats in the model group were significantly reduced, which were (3 049.48±590.62), (67.27±12.99), (2 058.00±417.46), (43.10±11.12) and (27.98±14.40) μg·g-1, respectively (P<0.05, P<0.01). Compared with the model group, the contents of isovaleric acid and caproic acid in the cecum contents of rats in the experimental group were significantly increased, which were (90.59±26.03) and (60.05±19.89) μg·g-1, respectively (all P<0.01).
Honey-processed Hedysari Radix can play a role in strengthening the spleen and replenishing qi by improving the metabolism level of cecal contents, regulating the metabolism levels of SCFAs in cecal contents, protecting the intestinal mucosal barrier, and reducing intestinal inflammation.
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