Sinus arrhythmia caused by pemetrexed with carboplatin combination: A case report.

Combination chemotherapy of pemetrexed and carboplatin is a standard treatment approach for non-small cell lung cancer (NSCLC). However, no prior reports have described cardiotoxicity associated with this therapeutic combination or sinus arrhythmia in oncological contexts. Here, we report the case of a 44-year-old female NSCLC patient that suffered from sinus arrhythmia following combined chemotherapeutic treatment with pemetrexed and carboplatin. The patient was successfully treated under medical guidance, and the condition was effectively reversed following the discontinuation of this chemotherapeutic regimen and medication prescribing. Overall, this represents a rare case of sinus arrhythmia in NSCLC patient during the first cycle of combined chemotherapy with pemetrexed and carboplatin. However, a putative etiological basis for this rare clinical entity remains to be established.

Risk Factors for Chemotherapy-Induced Peripheral Neuropathy Caused by Nanoparticle Albumin-Bound Paclitaxel in Advanced Breast Cancer.

Breast cancer (BC) is one of the most common malignancies affecting women and the leading cause of related mortality worldwide. An estimated 2260000 new cases of BC were diagnosed in 2020, which have seriously threatened the health. Paclitaxel (PTX), a natural product isolated from the bark of the pacific yew, has been found to be effective in treating advanced BC. Chemotherapy-induced peripheral neuropathy (CIPN), which refers to the damage to the peripheral nerves caused by exposure to a neurotoxic chemotherapeutic agent, is a common side effect affecting the patients undergoing PTX chemotherapy. Significant research efforts are needed to identify the various risk factors associated with CIPN. Here, a univariate analysis in BC patients with nanonab-PTX treatment was performed. The rate of CIPN in BC patients with albumin-bound paclitaxel (nab-PTX) for more than four weeks was significantly higher than that of patients with chemotherapy for less than four weeks. Moreover, the rate of CIPN in BC patients receiving nab-PTX first-line chemotherapy was remarkably higher than that in BC patients receiving paclitaxel as a sequence scheme. Taken together, chemotherapy cycles and the priority of nab-PTX-based chemotherapy can be considered the potential risk factors for CIPN induced by nab-PTX.

Risk Factors and Incidence of Malignancy After Kidney Transplant in Mainland China: A Single-Center Analysis.

OBJECTIVES: Malignancy is a common cause of death in renal transplant patients. The aim of this study was to investigate incidence, risk factors, and survival rates associated with posttransplant malignancy in kidney transplant recipients. MATERIALS AND METHODS: Between January 2015 and December 2020, 1154 patients underwent kidney transplant at the Affiliated Hospital of Qingdao University. Patients with a history of malignancy or other organ transplant(liver, pancreas, heart, orlungs) were excluded from this study. Patients with incomplete follow-up records were also excluded. Ultimately, our study comprised 811 kidney transplant recipients. The patient characteristics and incidence, type, and risk factors associated with posttransplant malignancy were examined. We also analyzed the overall survival of recipients with posttransplant malignancy. RESULTS: A total of 811 renal transplant recipients were followed up, with a median follow-up period of 3.0 years. Fourteen kidney recipients developed posttransplant malignancy (1.7%), with a mean time to malignancy diagnosis of 2.7 years. The 3-year and 5-year overall survival rates were 91.7% and 91.7%, respectively, in recipients with malignancy and 99.2% and 98.8%, respectively, in recipients without malignancy. The overall survival rate was significantly higher in recipients without malignancy than in those with malignancy (P = .03). Female sex, older recipient age, and history of prior kidney transplant were significant predictors of malignancy development. CONCLUSIONS: Postoperative malignancy in kidney transplantrecipients was associated with lower overall survival rates. Malignancy screening is important for kidney transplant patients, especially for older women and patients with a history of prior kidney transplant.

Malus toringoides (Rehd.) Hughes improves glucose and lipid metabolism and liver injury in high fructose-induced mice.

Malus toringoides (Rehd.) Hughes, as a traditional medicinal and edible plant used in Tibet, China, is used to treat hypertension, hyperlipidemia, and liver diseases. In recent decades, excessive fructose intake with diet has greatly increased the occurrence of a series of metabolic diseases including obesity, insulin resistance, hypertension, and hyperlipidemia. The present study was designed to investigate the effects of an ethanol extract of M. toringoides (EMT) on glucose and lipid metabolism and liver injury in high fructose-induced mice. The C57BL/6J male mice were orally administrated with 30% fructose solution for 8 weeks, and EMT was given orally for another 8 weeks. The level of liver lipids related parameters, hepatic oxidative stress, and inflammatory mediators was detected by the kits. The improving effects of EMT on liver injury and lipid accumulation of mice were observed by hematoxylin and eosin staining and Oil Red O staining. In vitro, the hypolipidemic effect of EMT on palmitic acid-induced HepG2 cells was detected by the kits and Oil Red O staining. Our results showed that EMT has the hypolipidemic effect in vivo and in vitro, and can improve liver injury caused by fructose intake though ameliorating oxidative stress and inflammatory responses. Thus, we suggested that EMT may be a candidate therapeutic agent to improve a series of metabolic diseases including obesity, insulin resistance, and hyperlipidemia. PRACTICAL APPLICATIONS: Our study was aimed to find a novel candidate drug for liver diseases using natural products. We assessed the protective effects of Malus toringoides (Rehd.) Hughes in the pathogenesis of glucose and lipid metabolism. In vivo, the plant significantly improved the disorder of blood lipid and blood glucose, and liver injury in mice induced by fructose, and in vitro, this plant significantly improved the lipid accumulation of HepG2 cells induced by palmitic acid. To sum up, our studies suggested that the plant may be beneficial in the prevention and management of diet-induced abnormal glucose and lipid metabolism and liver diseases. Therefore, it will be a candidate therapeutic agent to improve liver diseases.

Ursolic acid exhibits anti-inflammatory effects through blocking TLR4-MyD88 pathway mediated by autophagy.

There is an urgent need for effective treatments to reduce the large and growing burden of acute kidney injury (AKI) and its consequences. Inflammation is believed to play a vital role in the pathophysiology of AKI. Macrophage autophagy is considered protective against inflammation. Previous study discovered that ursolic acid (UA), a natural pentacyclic triterpene carboxylic acid found in many plants as apples, bilberries, cranberries and so on, promoted cancer cell autophagy. In the present study, we aimed to explore the effect of UA on ameliorating AKI and the role of macrophage autophagy in the context of inflammation. The data from in vivo experiments showed that pretreatment of mice with UA significantly suppressed xylene-induced ear oedema as well as protected against LPS-induced AKI. Related mechanisms were further studied through in vitro experiment. As expected, UA decreased inflammatory factors TNF-α, IL-6 and IL-1ß secretion in macrophages in response to lipopolysaccharide (LPS) stimulation. Furthermore, UA blocked LPS-induced TLR4/MyD88 pathway. More importantly, enhanced autophagy of macrophages by UA through increasing the expression of both LC3B and Beclin-1 led to alter macrophage function. What is more, similar to UA, autophagy inhibitor 3-MA obviously decreased inflammation factors releases hinting the vital role of autophagy in regulating inflammation. In all, above study suggested that UA is a potential anti-inflammatory natural compound for treating AKI by inducing autophagy.

Quantification of 1D, a novel derivative of curcumin with potential antitumor activity, in rat plasma by liquid chromatography-tandem mass spectrometry: application to a pharmacokinetic study in rats.

CONTEXT: 1 D is a novel derivative of curcumin and shows very promising antitumor activities in various cancer cell lines. OBJECTIVE: To characterize its preclinical pharmacokinetic profiles, a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of 1 D in rat plasma. MATERIALS AND METHODS: An aliquot of 50 µL plasma sample was processed by protein precipitation with methanol. Chromatographic separation was accomplished on a Zorbax Eclipse Plus C18 column (2.1 mm × 50 mm, 1.8 µm) with a gradient elution system (water/0.1% formic acid and methanol). Detection was performed by multiple reaction monitoring (MRM) mode using electrospray ionization in the positive ion mode. The optimized fragmentation transition for 1 D was m/z 491.2 â†’ 361.2. RESULTS: The method was linear over the concentration range of 5-1000 ng/mL. The intra- and inter-day precisions were less than 9.8% and the accuracy was within ± 14.5%. The mean recovery of 1 D ranged from 102.5 to 105.9%. No matrix effects and significant sample loss during sample processing were observed. The validated method has been successfully applied to a pharmacokinetic study in rats after intravenous administration of 1 D. Non-compartmental pharmacokinetic parameters, including half-life (t1/2), apparent volume of distribution (Vz), clearance (CLz), and area under the concentration-time curve (AUC(0-t)) were 4.92 h, 46.56 L/kg, 6.33 L/h/kg, and 806.70 µg/L/h, respectively. DISCUSSION AND CONCLUSIONS: Results demonstrated that 1 D displayed favourable pharmacokinetic properties for further in vivo pharmacologic evaluation, which could be facilitated by the validated LC-MS/MS method.

Some pharmacokinetic parameters of salvianolic acid A following single-dose oral administration to rats.

CONTEXT: Salvianolic acid A (Sal A) is a hydrophilic bioactive compound isolated from Salvia miltiorrhiza Bunge (Lamiaceae). It exerts beneficial effects after oral administration on diabetic complications. OBJECTIVE: To systematically study the absorption, distribution and excretion of Sal A after single-dose oral administration. MATERIALS AND METHODS: Animal experiments were conducted in Sprague-Dawley rats. Plasma was sampled at designated times after oral doses of 5, 10 and 20 mg/kg, and an intravenous dose of 50 µg/kg. Tissues were harvested at 10, 60 and 120 min postdosing. Bile, urine and feces were collected at specified intervals before and after dosing. Absorption and distribution characteristics were analyzed by LC-MS, and excretion characteristics were analyzed by UPLC-MS/MS. The Caco-2 cell model was applied to investigate potential mechanisms. RESULTS: The Cmax (5 mg/kg: 31.53 µg/L; 10 mg/kg: 57.39 µg/L; 20 mg/kg: 111.91 µg/L) of Sal A increased linearly with doses (r> 0.99). The calculated absolute bioavailability was 0.39-0.52%. Transport experiment showed poor permeability and the ratio of PB-A to PA-B was 3.13-3.97. The highest concentration of Sal A was achieved in stomach followed by small intestine and liver, and it could also be detected in brain homogenate. Approximately 0.775% of its administered dose was excreted via feces, followed by bile (0.00373%) and urine (0.00252%). DISCUSSION AND CONCLUSIONS: These results support the future development of Sal A as an oral drug for the treatment of diabetic complications. Future research should be conducted to investigate the reason for its poor bioavailability and improve this situation.

Anti-Inflammatory Activity of Epimedium brevicornu Maxim Ethanol Extract.

Epimedium brevicornu Maxim has been used as a traditional herbal drug in China. In this study, the anti-inflammatory effects of E. brevicornu Maxim ethanol extract (EBME) were investigated in RAW264.7 macrophages and mice challenged with lipopolysaccharide (LPS). Results showed that EBME attenuated inflammation by decreasing the production of several proinflammatory mediators, such as nitric oxide (NO), prostaglandin (PG) E2, inducible nitric oxide synthase, and cyclooxygenase-2, in LPS-stimulated RAW264.7 macrophages. EBME increased the expression of heme oxygenase-1 (HO-1) and promoted the nuclear translocation of nuclear factor erythroid 2-related factor 2. The inhibitory effects of EBME on LPS-stimulated NO and PGE2 expression were partially reversed by HO-1 inhibitor. EBME also elicited an anti-inflammatory effect by inhibiting the production of tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6 in LPS-induced peritonitis. Therefore, EBME exhibited anti-inflammatory effects in vitro and in vivo.

Ubenimex suppresses Pim-3 kinase expression by targeting CD13 to reverse MDR in HCC cells.

Hepatocellular carcinoma (HCC) is one of the most serious cancers, with rapid progression and high mortality. However, chemotherapy of HCC is hindered by multi-drug resistance (MDR). It is urgent, therefore, to explore new approaches for overcoming MDR of HCC cells. Ubenimex, an inhibitor of CD13, has been used as an immuno-enhancer for treating hematological neoplasms and other solid tumors. Here, we demonstrate that Ubenimex can also reverse MDR in the HCC cell lines HepG2/5-FU and Bel7402/5-FU. Ubenimex inhibits the expression of the proto-oncogene, Pim-3, which is accompanied by decreased expression of BCL-2 and BCL-XL, decreased phosphorylation of Bad, and increased tumor apoptosis. Moreover, Ubenimex decreases expression of the MDR-associated proteins P-gp, MRP3 and MRP2 to enhance intracellular accumulation of Cisplatin, for which down-regulation of Pim-3 is essential. Our results reveal a previously uncharacterized function of Ubenimex in mediating drug resistance in HCC, which suggests that Ubenimex may provide a new strategy to reverse MDR and improve HCC sensitivity to chemotherapeutic drugs via its effects on Pim-3.

Rhamnella gilgitica Attenuates Inflammatory Responses in LPS-Induced Murine Macrophages and Complete Freund's Adjuvant-Induced Arthritis Rats.

Rhamnella gilgitica Mansf. et Melch, which belongs to the rhamnus family (Rhamnaceae), is traditionally used to treat rheumatism, swelling and pain in China. However, little is known about the pharmacological activities of this plant. The anti-inflammatory activities of the 70% ethanol extract of R. gilgitica (RG) in RAW264.7 macrophages and complete Freund's adjuvant (CFA)-induced arthritic rats are investigated in this study for the first time. The effects of RG on cell viability were determined by a MTT assay, and the effects of RG on pro-inflammatory mediators were analyzed by ELISA and Western blot. The effects of RG on paw thickness, thymus and spleen index were also examined in CFA-induced arthritic rats. RG suppressed the induction of proinflammatory mediators, including iNOS (inducible nitric oxide synthase), NO (nitric oxide), COX-2 (cyclooxygenase-2) and PG (prostaglandin) E2 in LPS stimulated RAW264.7 macrophages. RG also inhibited the phosphorylation and degradation of I[Formula: see text]B-[Formula: see text], as well as the nuclear translocation of nuclear factor kappa B (NF-[Formula: see text]B) p65. In addition, RG treatment significantly reduced the paw thickness in CFA-induced arthritic rats. Oral administration of RG led to a significant decrease of both the thymus and spleen index at a concentration of 100[Formula: see text]mg/mL. Taken together, these findings suggest that RG might be an agent for further development in the treatment of a variety of inflammatory diseases.

[Effect of seaweed pigment glycoprotein on the expression of PCNA and Bcl-2 protein in hepatocarcinoma cells in mice].

OBJECTIVE: To investigate the effect of seaweed pigment glycoprotein (SPG) on the expression of PCNA and Bcl-2 protein in hepatocarcinoma cells in mice. METHODS: Fifty mice inoculated with hepatocarcinoma cells were divided into five groups, 10 mice in each group. SPG was given by gavage at the dosage of 100, 50 and 10 mg/kg everyday to high, medium and low dose group respectively, normal saline was given orally to tumor control group, and cyclophosphamide 20 mg/kg was injected to the cylophosphamide group every the other day, all mice were sacrificed 10 days later. The proliferation activity of hepatocarcinoma cells was determined by MTT assay, and the expression of proliferating cell nuclear antigen (PCNA) and Bcl-2 protein were measured by immunohistochemical method. RESULTS: The cell proliferation activity expressed by the optical density of the high-dose group and tumor control group were 0.711 +/- 0.028 and 1.135 +/- 0.032 respectively (P < 0.05). The expression of PCNA and Bcl-2 protein in high-dose group was 28.32% and 16.78% respectively, and that in tumor control group was 72.78% and 65.16% respectively (P < 0.05). CONCLUSION: The proliferation activity of hepatocarcinoma cells in mice could be reduced and the expression of PCNA and Bcl-2 protein could be inhibited by SPG.