High Prevalence of A-ß+ Ketosis-Prone Diabetes in Children with Type 2 Diabetes and Diabetic Ketoacidosis at Diagnosis: Evidence from the Rare and Atypical Diabetes Network (RADIANT).

Background: A-ß+ ketosis-prone diabetes (KPD) in adults is characterized by presentation with diabetic ketoacidosis (DKA), negative islet autoantibodies, and preserved ß-cell function in persons with a phenotype of obesity-associated type 2 diabetes (T2D). The prevalence of KPD has not been evaluated in children. We investigated children with DKA at "T2D" onset and determined the prevalence and characteristics of pediatric A-ß+ KPD within this cohort. Methods: We reviewed the records of 716 children with T2D at a large academic hospital and compared clinical characteristics of those with and without DKA at onset. In the latter group, we identified patients with A-ß+ KPD using criteria of the Rare and Atypical Diabetes Network (RADIANT) and defined its prevalence and characteristics. Results: Mean age at diagnosis was 13.7 ± 2.4 years: 63% female; 59% Hispanic, 29% African American, 9% non-Hispanic White, and 3% other. Fifty-six (7.8%) presented with DKA at diagnosis and lacked islet autoantibodies. Children presenting with DKA were older and had lower C-peptide and higher glucose concentrations than those without DKA. Twenty-five children with DKA (45%) met RADIANT A-ß+ KPD criteria. They were predominantly male (64%), African American or Hispanic (96%), with substantial C-peptide (1.3 ± 0.7 ng/mL) at presentation with DKA and excellent long-term glycemic control (HbA1c 6.6% ± 1.9% at follow-up (median 1.3 years postdiagnosis)). Conclusions: In children with a clinical phenotype of T2D and DKA at diagnosis, approximately half meet criteria for A-ß+ KPD. They manifest the key characteristics of obesity, preserved ß-cell function, male predominance, and potential to discontinue insulin therapy, similar to adults with A-ß+ KPD.

Lack of Association of A1C With Postoperative Complications in Children With Type 1 or Type 2 Diabetes.

Not meeting recommended A1C targets may be associated with postoperative complications in adults, but there are no studies reporting on the relationship between preoperative A1C and postoperative complications in children with type 1 or type 2 diabetes. The objective of this study was to determine whether elevated A1C levels were associated with an increased incidence of postoperative complications in children with diabetes presenting for elective noncardiac surgery or diagnostic procedures. It found no such association, suggesting no need to delay elective surgery in children with diabetes until A1C is optimized.

Associations of insulin sensitivity and immune inflammatory responses with child blood lead (Pb) and PM2.5 exposure at an e-waste recycling area during the COVID-19 lockdown.

Fine particular matter (PM2.5) and lead (Pb) exposure can induce insulin resistance, elevating the likelihood of diabetes onset. Nonetheless, the underlying mechanism remains ambiguous. Consequently, we assessed the association of PM2.5 and Pb exposure with insulin resistance and inflammation biomarkers in children. A total of 235 children aged 3-7 years in a kindergarten in e-waste recycling areas were enrolled before and during the Corona Virus Disease 2019 (COVID-19) lockdown. Daily PM2.5 data was collected and used to calculate the individual PM2.5 daily exposure dose (DED-PM2.5). Concentrations of whole blood Pb, fasting blood glucose, serum insulin, and high mobility group box 1 (HMGB1) in serum were measured. Compared with that before COVID-19, the COVID-19 lockdown group had lower DED-PM2.5 and blood Pb, higher serum HMGB1, and lower blood glucose and homeostasis model assessment of insulin resistance (HOMA-IR) index. Decreased DED-PM2.5 and blood Pb levels were linked to decreased levels of fasting blood glucose and increased serum HMGB1 in all children. Increased serum HMGB1 levels were linked to reduced levels of blood glucose and HOMA-IR. Due to the implementation of COVID-19 prevention and control measures, e-waste dismantling activities and exposure levels of PM2.5 and Pb declined, which probably reduced the association of PM2.5 and Pb on insulin sensitivity and diabetes risk, but a high level of risk of chronic low-grade inflammation remained. Our findings add new evidence for the associations among PM2.5 and Pb exposure, systemic inflammation and insulin resistance, which could be a possible explanation for diabetes related to environmental exposure.

The effects of patchouli alcohol and combination with cisplatin on proliferation, apoptosis and migration in B16F10 melanoma cells.

Melanoma is a highly metastatic cancer with a low incidence rate, but a high mortality rate. Patchouli alcohol (PA), a tricyclic sesquiterpene, is considered the main active component in Pogostemon cablin Benth, which improves wound healing and has anti-tumorigenic activity. However, the pharmacological action of PA on anti-melanoma remains unclear. Thus, the present study aimed to investigate the role of PA in the proliferation, cell cycle, apoptosis and migration of melanoma cells. These results indicated that PA selectively inhibited the proliferation of B16F10 cells in a dose- and time-dependent manner. It induced cell cycle arrest at the G0 /G1 phase and typical morphological changes in apoptosis, such as chromatin condensation, DNA fragmentation and apoptotic bodies. In addition, PA reduced the migratory ability of B16F10 cells by upregulating E-cadherin and downregulating p-Smad2/3, vimentin, MMP-2 and MMP-9 expression. PA was also found to strongly suppress tumour growth in vivo. Furthermore, PA combined with cisplatin synergistically inhibited colony formation and migration of B16F10 cells and attenuated the development of resistance to treatment. Therefore, the results of this study indicate that PA may play a pivotal role in inducing apoptosis and reducing the migration of melanoma cells, and may thus be a potential candidate for melanoma treatment.

Red Blood Cell Conservation and Use in the Cardiovascular Operating Rooms at Ben Taub General Hospital.

OBJECTIVES: A conservative hemoglobin transfusion threshold is noninferior to a liberal threshold in cardiac surgery. However, red blood cell (RBC) transfusion remains common during cardiac surgery. The authors' single-center, retrospective study aimed to decrease RBC transfusions for hemoglobin >7.5 g/dL in nonemergent cardiovascular surgeries utilizing cardiopulmonary bypass (CPB), by educating the anesthesiology and surgical staff on the benefits of a conservative threshold for transfusions, and incorporating the discussion and routine use of blood conservation methods for all nonemergent cardiac surgeries. DESIGN: This was a single-center, retrospective study that included all nonemergent coronary artery bypass grafting and single-valve cases utilizing CPB from January 2018 to December 2021 before and after the intervention in July 2019. SETTING: The data involved a single community hospital. PARTICIPANTS: A total of 417 patients were included in the study. INTERVENTIONS: The authors adopted a conservative threshold for blood transfusion and implemented a collaborative multidisciplinary approach to blood conservation. MEASUREMENTS AND MAIN RESULTS: Baseline patient characteristics were summarized, and the incidence of RBC transfusion before and after the intervention on July 26, 2019, were compared by Wilcoxon rank sum and chi-square tests. Multivariate logistic regression was used. The intervention was significantly associated with reduced RBC transfusion rate after adjusting for confounding variables (p < 0.05). The odds of receiving an RBC transfusion among patients after the intervention was 0.615 times the odds among patients before intervention (95% CI: 0.3913-0.9663). CONCLUSIONS: The authors' goal was to improve patient outcomes and the quality of perioperative care during cardiac surgery. By implementing a protocol and educating anesthesiologists, surgeons, and perfusionists, they successfully decreased the incidence of RBC transfusion above a hemoglobin of 7.5 g/dL.

Angelica sinensis extract induces telomere dysfunction, cell cycle arrest, and mitochondria-mediated apoptosis in human glioblastoma cells.

Glioblastoma (GB) is one of the most aggressive and malignant tumors of the central nervous system. Conventional treatment for GB requires surgical resection followed by radiotherapy combined with temozolomide chemotherapy; however, the median survival time is only 12-15 months. Angelica sinensis Radix (AS) is commonly used as a traditional medicinal herb or a food/dietary supplement in Asia, Europe, and North America. This study aimed to investigate the effect of AS-acetone extract (AS-A) on the progression of GB and the potential mechanisms underlying its effects. The results indicated that AS-A used in this study showed potency in growth inhibition of GB cells and reduction of telomerase activity. In addition, AS-A blocked the cell cycle at the G0/G1 phase by regulating the expression of p53 and p16. Furthermore, apoptotic morphology, such as chromatin condensation, DNA fragmentation, and apoptotic bodies, was observed in AS-A-treated cells, induced by the activation of the mitochondria-mediated pathway. In an animal study, AS-A reduced tumor volume and prolonged lifespans of mice, with no significant changes in body weight or obvious organ toxicity. This study confirmed the anticancer effects of AS-A by inhibiting cell proliferation, reducing telomerase activity, altering cell cycle progression, and inducing apoptosis. These findings suggest that AS-A has great potential for development as a novel agent or dietary supplement against GB.

Enhanced field-dependent conductivity and material properties of nano-AlN/micro-SiC/silicone elastomer hybrid composites for electric stress mitigation in high-voltage power modules.

This paper reports an enhancement of the nonlinear conductivity, thermal and mechanical properties of micro-silicon carbide/silicone elastomer (m-SiC/SE) composites by adding nano-aluminum nitride (n-AlN) for power module encapsulation applications. The electrical properties (such as nonlinear conductivity characteristics and transient permittivity obtained from polarization current, and trap distributions obtained from thermally stimulated depolarization current) and material properties (including thermo-gravimetric analysis, coefficient of thermal expansion (CTE), and thermal conductivity, tensile strength, strain at break and Young's modulus) of the pure SE, m-SiC/SE microcomposites, m-SiC/n-AlN/SE hybrid composites are investigated. The effect of the m-SiC fillers and n-AlN fillers on physicochemical properties of the SE matrix is analyzed by FT-IR spectroscopy and crosslinking degree. The measured nonlinear conductivity and transient permittivity are used for electric field simulation under DC stationary and square voltages. It is found that the addition of n-AlN fillers in the SE hybrid composite improves the nonlinear conductivity characteristics and mitigates the electric field under DC stationary and square voltages, compared to the SE microcomposite. Furthermore, the m-SiC/n-AlN/SE hybrid composite has a higher thermal degradation temperature, thermal conductivity, tensile strength, Young's modulus, and crosslinking degree than the SE microcomposite, whereas their CTE and strain at break are lower. It is elucidated that the m-SiC/n-AlN/SE hybrid composite with enhanced nonlinear conductivity and material properties is a promising packaging material for high-voltage power modules.

Predictors and outcomes of postoperative tracheostomy in patients undergoing acute type A aortic dissection surgery.

BACKGROUND: Despite surgical advances, acute type A aortic dissection remains a life-threatening disease with high mortality and morbidity. Tracheostomy is usually used for patients who need prolonged mechanical ventilation in the intensive care unit (ICU). However, data on the risk factors for requiring tracheostomy and the impact of tracheostomy on outcomes in patients after Stanford type A acute aortic dissection surgery (AADS) are limited. METHODS: A retrospective single-institutional study including consecutive patients who underwent AADS between January 2016 and December 2019 was conducted. Patients who died intraoperatively were excluded. Univariate analysis and multivariate logistic regression analysis were used to identify independent risk factors for postoperative tracheostomy (POT). A nomogram to predict the probability of POT was constructed based on independent predictors and their beta-coefficients. The area under the receiver operating characteristic curve (AUC) was performed to assess the discrimination of the model. Calibration plots and the Hosmer-Lemeshow test were used to evaluate calibration. Clinical usefulness of the nomogram was assessed by decision curve analysis. Propensity score matching analysis was used to analyze the correlation between requiring tracheostomy and clinical prognosis. RESULTS: There were 492 patients included in this study for analysis, including 55 patients (11.2%) requiring tracheostomy after AADS. Compared with patients without POT, patients with POT experienced longer ICU and hospital stay and higher mortality. Age, cerebrovascular disease history, preoperative white blood cell (WBC) count and renal insufficiency, intraoperative amount of red blood cell (RBC) transfusion and platelet transfusion were identified as independent risk factors for POT. Our constructed nomogram had good discrimination with an AUC = 0.793 (0.729-0.856). Good calibration and clinical utility were observed through the calibration and decision curves, respectively. For better clinical application, we defined four intervals that stratified patients from very low to high risk for occurrence of POT. CONCLUSIONS: Our study identified preoperative and intraoperative risk factors for POT and found that requiring tracheostomy was related to the poor outcomes in patients undergoing AADS. The established prediction model was validated with well predictive performance and clinical utility, and it may be useful for individual risk assessment and early clinical decision-making to reduce the incidence of tracheostomy.

Perspectives of internal medicine residency clinics: A national survey of US medical directors.

Background: Ambulatory training is an integral component of internal medicine residency programs, yet details regarding operational processes in resident continuity clinics remain limited. Methods: We surveyed a convenience sample of medical directors of residency practices between 2015 and 2019 (n = 222) to describe and share operational and scheduling processes in internal medicine resident continuity clinics in the US. Results: Among residency practices, support for the medical director role ranged substantially, but was most commonly reported at 11%-20% full-time-equivalent support. By the end of the survey period, the majority of programs (65.1%) reported obtaining patient-centered medical home (PCMH) certification (level 1-3). For new patient appointments, 34.9% of programs reported a 1-7 day wait and 25.8% reported an 8-14 day wait. Wait times for new appointments were generally shorter for PCMH certified practices (P = 0.029). No-show rates were most commonly 26%-50% for new patients and 11%-25% for established patients. Most programs reported that interns see 3-4 patients per ½-day and senior residents see 5-6 patients per ½-day. Most interns and residents maintain a panel size of 51-120 patients. Discussion: Creating high-performing residency clinics requires a focus on core building blocks and operational processes. Based on the survey results and consensus opinion, we provide five summary recommendations related to (1) support for the medical director leadership role, (2) patient-centered and coordinated models of care, (3) support for patient scheduling, (4) recommended visit lengths, and (5) ancillary support, such as social work.

Risk factors and in-hospital mortality of postoperative hyperlactatemia in patients after acute type A aortic dissection surgery.

BACKGROUND: Hyperlactatemia may be caused by increased production due to tissue hypoxia or non-hypoxia. The aim of this study was first to identify risk factors for postoperative hyperlactatemia (POHL) after Stanford type A acute aortic dissection surgery (AADS) and construct a predictive model, and second to evaluate the impact of POHL on prognosis. METHODS: This retrospective study involved patients undergoing AADS from January 2016 to December 2019 in Wuhan Union Hospital. Multivariate logistic regression analysis was performed to identify independent risk factors for POHL. A nomogram predicting POHL was established based on these factors and was validated in the original dataset. The receiver operating characteristic curve was drawn to assess the ability of postoperative lactate levels to predict the in-hospital mortality. RESULTS: A total of 188 patients developed POHL after AADS (38.6%). Male gender, surgery history, red blood cell transfusion and cardiopulmonary bypass time were identified as independent predictors. The C-index of the prediction model for POHL was 0.72, indicating reasonable discrimination. The model was well calibrated by visual inspection and goodness-of-fit test (Hosmer-Lemeshow χ2 = 10.25, P = 0.25). Decision and clinical impact curves of the model showed good clinical utility. The overall in-hospital mortality rate was 10.1%. Postoperative lactate levels showed a moderate predictive power for postoperative in-hospital mortality (C-index: 0.72). CONCLUSION: We developed and validated a prediction model for POHL in patients undergoing AADS, which may have clinical utility in personal risk evaluation and preventive interventions. The POHL could be a good predictor for in-hospital mortality.

Enhancement of cytotoxicity and induction of apoptosis by cationic nano-liposome formulation of n-butylidenephthalide in breast cancer cells.

Breast cancer is the second most common malignancy in women. Current clinical therapy for breast cancer has many disadvantages, including metastasis, recurrence, and poor quality of life. Furthermore, it is necessary to find a new therapeutic drug for breast cancer patients to meet clinical demand. n-Butylidenephthalide (BP) is a natural and hydrophobic compound that can inhibit several tumors. However, BP is unstable in aqueous or protein-rich environments, which reduces the activity of BP. Therefore, we used an LPPC (Lipo-PEG-PEI complex) that can encapsulate both hydrophobic and hydrophilic compounds to improve the limitation of BP. The purpose of this study is to investigate the anti-tumor mechanisms of BP and BP/LPPC and further test the efficacy of BP encapsulated by LPPC on SK-BR-3 cells. BP inhibited breast cancer cell growth, and LPPC encapsulation (BP/LPPC complex) enhanced the cytotoxicity on breast cancer by stabilizing the BP activity and offering endocytic pathways. Additionally, BP and LPPC-encapsulated BP induced cell cycle arrest at the G0/G1 phase and might trigger both extrinsic as well as intrinsic cell apoptosis pathway, resulting in cell death. Moreover, the BP/LPPC complex had a synergistic effect with doxorubicin of enhancing the inhibitory effect on breast cancer cells. Consequently, LPPC-encapsulated BP could improve the anti-cancer effects on breast cancer in vitro. In conclusion, BP exhibited an anti-cancer effect on breast cancer cells, and LPPC encapsulation efficiently improved the cytotoxicity of BP via an acceleration of entrapment efficiency to induce cell cycle block and apoptosis. Furthermore, BP/LPPC exhibited a synergistic effect in combination with doxorubicin.

Juniperus indica Bertol. extract synergized with cisplatin against melanoma cells via the suppression of AKT/mTOR and MAPK signaling and induction of cell apoptosis.

Juniperus indica Bertol. is an herbal plant that belongs to the genus Juniperus, which is commonly used in traditional medicine to refresh the mind and for diuretic use. However, few studies have reported the function of J. indica Bertol. Hence, this study aimed to investigate the anti-tumor and synergistic potential of J. indica Bertol. extract (JIB extract) for melanoma cells. Our results indicated the anti-melanoma activity of JIB extract. JIB extract induced cell cycle arrest at the G0/G1 phase and decreased cyclin and cdk protein expressions. In addition, AKT/mTOR signaling and MAPK signaling were inhibited by JIB extract to suppress melanoma cell growth and proliferation. Additionally, JIB extract induced B16/F10 cell apoptosis via the caspase cascade. According to the JIB extract's anti-melanoma capacity, to assess the synergistic effects of cisplatin and JIB extract. The results demonstrated that JIB extract combined with cisplatin enhanced the inhibition of cell growth, proliferation, and survival through the obstruction of cell cycle progression and AKT/mTOR and MAPK signaling as well as the induction of cell apoptosis. Collectively, our results indicate that JIB extract showed anti-tumor effects and synergized with cisplatin against B16/F10 cells, indicating the possibility of JIB extract to be developed as adjuvant therapy for melanoma.

Cedrus atlantica Extract Suppress Glioblastoma Growth through Promotion of Genotoxicity and Apoptosis: In Vitro and In Vivo Studies.

Glioblastoma (GBM) is the most common malignant primary brain tumor in humans, exhibiting highly infiltrative growth and drug resistance to conventional chemotherapy. Cedrus atlantica (CAt) extract has been shown to decrease postoperative pain and inhibit the growth of K562 leukemia cells. The aim of this study was to assess the anti-GBM activity and molecular mechanism of CAt extract in vitro and in vivo. The results showed that CAt extract greatly suppressed GBM cells both in vitro and in vivo and enhanced the survival rate in subcutaneous and orthotopic animal models. Moreover, CAt extract increased the level of ROS and induced DNA damage, resulting in cell cycle arrest at the G0/G1 phase and cell apoptosis. Western blotting results indicated that CAt extract regulates p53/p21 and CDK4/cyclin D1 protein expression and activates extrinsic and intrinsic apoptosis. Furthermore, CAt extract enhanced the cytotoxicity of Temozolomide and decreased AKT/mTOR signaling by combination treatment. In toxicity assays, CAt extract exhibited low cytotoxicity toward normal cells or organs in vitro and in vivo. CAt extract suppresses the growth of GBM by induction of genotoxicity and activation of apoptosis. The results of this study suggest that CAt extract can be developed as a therapeutic agent or adjuvant for GBM treatment in the future.

A Pulsatile Chest Mass After Bentall Procedure: A Case Report.

Aortic dissection is an aggressive and life-threatening cardiac disease that's highly challenging in surgical operation. Bentall procedure comes with potential complications. How to manage these complications is important when it comes to improving patient outcome. In this case, we present a 41-year-old male patient with iatrogenic aortic dissection. He had aortic valve replacement and repair of an atrial septal defect in 2012. After five years, he suffered reoperation for aortic dissection. A year later, the patient was readmitted for a voluminous pulsatile mass over the anterior thorax, confirming the presence of a huge pseudoaneurysm originating from the left coronary bottom performed during the Bentall procedure. This required a third operation to repair the hemorrhagic site. Pseudoaneurysm is a common complication after the inclusion technique in the Bentall procedure. Effective hemostasis or tension-free anastomosis is important toward improving patient outcome.

Reoperation after Implanting a Triple-Branched Stent Graft: Case Report.

Acute type A aortic dissection (ATAAD) is an aortic catastrophe with high mortality, requiring immediate surgical intervention. Recently, placement of a triple-branch stent graft has emerged as an effective technique for total arch reconstruction. Indications for this approach, however, are limited by various complications, such as endoleak, stent graft migration or kinking, and spontaneous thrombosis. Here, we report a case of Marfan syndrome in which the patient underwent a reoperation owing to frame fractures (or degradation of graft material) in a triple-branched stent graft implanted 5 years earlier.

Effects of Cedrus atlantica extract on acute myeloid leukemia cell cycle distribution and apoptosis.

This study investigated the anti-leukemic effects of Cedrus atlantica extract (CAt extract) on cell cycle distribution and apoptosis in human acute myeloid leukemia (AML) cells. AML often occurs in older adults, accounting for 60% of the cases, and is likely to be resistant to chemotherapy due to multidrug resistance, resulting in early death during cancer treatment. With the increasing focus on prevention medicine, natural plant components are being used as a major source for the development of therapeutic drugs or functional foods to cure or alleviate the disease. Cedrus species are known to have anti-inflammatory, antimicrobial, antiviral, and anticancer effects; however, the anticancer effects of CAt extract have not been elucidated. In this study, CAt extract demonstrated an inhibitory effect on human leukemia cells in a concentration-dependent manner; CAt extract induced G0/G1 phase arrest via restrained protein levels of p-Rb and cell cycle-related proteins. After CAt extract exposure, the extrinsic and intrinsic apoptotic pathways were activated through caspase-8, -9, and -3 cleavage. Additionally, CAt extract suppressed VEGF, MMP-2, and MMP-9 expression. This study demonstrated that CAt extract treatment significantly reduced cell growth, cell cycle arrest in the G0/G1 phase, and induction of apoptosis, leading to leukemia cell death.

Cedrol, a Sesquiterpene Alcohol, Enhances the Anticancer Efficacy of Temozolomide in Attenuating Drug Resistance via Regulation of the DNA Damage Response and MGMT Expression.

Glioblastoma (GBM) is a common and aggressive brain tumor with a median survival of 12-15 months. Temozolomide (TMZ) is a first-line chemotherapeutic agent used in GBM therapy, but the occurrence of drug resistance limits its antitumor activity. The natural compound cedrol has remarkable antitumor activity and is derived from Cedrus atlantica. In this study, we investigated the combined effect of TMZ and cedrol in GBM cells in vitro and in vivo. The TMZ and cedrol combination treatment resulted in consistently higher suppression of cell proliferation via regulation of the AKT and MAPK signaling pathways in GBM cells. The combination treatment induced cell cycle arrest, cell apoptosis, and DNA damage better than either drug alone. Furthermore, cedrol reduced the expression of proteins associated with drug resistance, including O6-methlyguanine-DNA-methyltransferase (MGMT), multidrug resistance protein 1 (MDR1), and CD133 in TMZ-treated GBM cells. In the animal study, the combination treatment significantly suppressed tumor growth through the induction of cell apoptosis and decreased TMZ drug resistance. Moreover, cedrol-treated mice exhibited no significant differences in body weight and improved TMZ-induced liver damage. These results imply that cedrol may be a potential novel agent for combination treatment with TMZ for GBM therapy that deserves further investigation.

Lipoplex-based targeted gene therapy for the suppression of tumours with VEGFR expression by producing anti-angiogenic molecules.

BACKGROUND: The anti-angiogenic fusion protein RBDV-IgG1 Fc (RBDV), which comprises the receptor-binding domain of vascular endothelial growth factor-A (VEGF-A), has shown antitumour effects by reducing angiogenesis in vivo. This study used the cationic lipoplex lipo-PEG-PEI-complex (LPPC) to simultaneously encapsulate both the RBDV targeting protein and the RBDV plasmid (pRBDV) without covalent bonds to assess VEGFR targeting gene therapy in mice with melanoma in vivo. RESULTS: LPPC protected the therapeutic transgene from degradation by DNase, and the LPPC/RBDV complexes could specifically target VEGFR-positive B16-F10 cells both in vitro and in vivo. With or without RBDV protein-targeting direction, the pRBDV-expressing RBDV proteins were expressed and reached a maximal concentration on the 7th day in the sera after transfection in vivo and significantly elicited growth suppression against B16-F10 melanoma but not IgG1 control proteins. In particular, LPPC/pRBDV/RBDV treatment with the targeting molecules dramatically inhibited B16-F10 tumour growth in vivo to provide better therapeutic efficacy than the treatments with gene therapy with IgG1 protein targeting or administration of a protein drug with RBDV. CONCLUSIONS: The simultaneous combination of the LPPC complex with pRBDV gene therapy and RBDV protein targeting might be a potential tool to conveniently administer targeted gene therapy for cancer therapy.

Pogostemon cablin Triggered ROS-Induced DNA Damage to Arrest Cell Cycle Progression and Induce Apoptosis on Human Hepatocellular Carcinoma In Vitro and In Vivo.

The purpose of the study was to elucidate the anti-hepatoma effects and mechanisms of Pogostemon cablin essential oils (PPa extract) in vitro and in vivo. PPa extract exhibited an inhibitory effect on hepatocellular carcinoma (HCC) cells and was less cytotoxic to normal cells, especially normal liver cells, than it was to HCC cells, exerting a good selective index. Additionally, PPa extract inhibited HCC cell growth by blocking the cell cycle at the G0/G1 phase via p53 dependent or independent pathway to down regulated cell cycle regulators. Moreover, PPa extract induced the FAS-FASL-caspase-8 system to activate the extrinsic apoptosis pathway, and it increased the bax/bcl-2 ratio and reduced ΔΨm to activate the intrinsic apoptosis pathway that might be due to lots of reactive oxygen species (ROS) production which was induced by PPa extract. In addition, PPa extract presented to the potential to act synergistically with sorafenib to effectively inhibit HCC cell proliferation through the Akt/mTOR pathway and reduce regrowth of HCC cells. In an animal model, PPa extract suppressed HCC tumor growth and prolonged lifespan by reducing the VEGF/VEGFR axis and inducing tumor cell apoptosis in vivo. Ultimately, PPa extract demonstrated nearly no or low system-wide, physiological, or pathological toxicity in vivo. In conclusion, PPa extract effectively inhibited HCC cell growth through inducing cell cycle arrest and activating apoptosis in vitro and in vivo. Furthermore, PPa extract exhibits less toxicity toward normal cells and organs than it does toward HCC cells, which might lead to fewer side effects in clinical applications. PPa extract may be developed into a clinical drug to suppress tumor growth or functional food to prevent HCC initiation or chemoprotection of HCC recurrence.

Extract of Juniperus indica Bertol Synergizes with Cisplatin to Inhibit Oral Cancer Cell Growth via Repression of Cell Cycle Progression and Activation of the Caspase Cascade.

Oral cancer-a type of head and neck cancer-is estimated to be the fifth most common cancer in Taiwan. However, efficacious therapies for oral cancer are still lacking due to drug resistance and recurrence. Consequently, the identification of new anticancer agents for clinical treatment is needed. Juniperus indica Bertol is a plant of the Juniperus genus often used as a treatment in traditional medicine due to its anti-inflammatory, antibacterial and diuretic functions. The biofunctions of Juniperus indica Bertol including its anticancer potential, have not been fully explored. As a result, the aim of this research was to investigate the anticancer activity of Juniperus indica Bertol extract (JIB extract) and determine whether JIB extract has synergistic effects with cisplatin in oral cancer. These results are the first to demonstrate that JIB extract exhibits anticancer capacity and synergizes with cisplatin to treat oral cancer. Our findings indicate that JIB extract has a potential to develop anticancer agent and chemo therapeutic adjuvant for oral cancer.