Novel strategies to reverse chemoresistance in colorectal cancer.

Colorectal cancer (CRC) is a common gastrointestinal malignancy with high morbidity and fatality. Chemotherapy, as traditional therapy for CRC, has exerted well antitumor effect and greatly improved the survival of CRC patients. Nevertheless, chemoresistance is one of the major problems during chemotherapy for CRC and significantly limits the efficacy of the treatment and influences the prognosis of patients.

Interactions between and the resident microbiota.

is a prevalent, opportunistic human fungal pathogen. It usually dwells in the human body as a commensal, however, once in its pathogenic state, it causes diseases ranging from debilitating superficial to life-threatening systemic infections. The switch from harmless colonizer to virulent pathogen is, in most cases, due to perturbation of the fungus-host-microbiota interplay.

[Involvement of PI 3 K/Akt/mTOR Signaling in Protective Effects of Moxibustion for Premature Ovarian Failure in Rats].

Objective: To study the protective effect of moxibustion for tripterygium-induced premature ovarian failure (POF) and its underlying mechanisms in rats.

Methods: Forty-five female SD rats were randomly divided into normal control, POF model and moxibustion groups (＝15/group). The POF model was induced by intragastric administration of Triptolide (40 mg/kg), once daily for 6 weeks.

Acute liver failure enhances oral plasma exposure of zidovudine in rats by downregulation of hepatic UGT2B7 and intestinal P-gp.

HIV infection is often associated with liver failure, which alters the pharmacokinetics of many drugs. In this study we investigated whether acute liver failure (ALF) altered the pharmacokinetics of the first-line anti-HIV agent zidovudine (AZT), a P-gp/BCRP substrate, in rats. ALF was induced in rats by injecting thioacetamide (TAA, 300 mg·kg·d, ip) for 2 days.

Evaluating antithrombotic activity of HY023016 on rat hypercoagulable model.

The generation of thrombus is not considered as an isolated progression without other pathologic processes, which may also enhance procoagulant state. The purpose of this study was to assess whether HY023016, a novel dabigatran prodrug and an oral direct thrombin inhibitor, or dabigatran etexilate, another thrombin inhibitor can improve the state of whole blood hypercoagulability in vitro/vivo. By using whole blood flow cytometry we explored the effects of HY023016 and dabigatran etexilate on thrombin and ADP-induced human platelet-leukocyte aggregation generated in vitro.

Chronic administration of caderofloxacin, a new fluoroquinolone, increases hepatic CYP2E1 expression and activity in rats.

Aim: Caderofloxacin is a new fluoroquinolone that is under phase III clinical trials in China. Here we examined the effects of caderofloxacin on rat hepatic cytochrome P450 (CYP450) isoforms as well as the potential of caderofloxacin interacting with co-administered drugs.

Methods: Male rats were treated with caderofloxacin (9 mg/kg, ig) once or twice daily for 14 consecutive days.

PPARγ agonists regulate bidirectional transport of amyloid-β across the blood-brain barrier and hippocampus plasticity in db/db mice.

Background And Purpose: There is emerging evidence suggesting that abnormal transport of amyloid-β (Aβ) across the blood-brain barrier (BBB) is involved in diabetes-associated cognitive decline. We investigated whether PPARγ agonists restore Aβ transport across the BBB and hippocampal plasticity in db/db mice.

Experimental Approach: Efflux and influx of Aβ across the BBB were determined by stereotaxic intra-cerebral or i.

Hippocampal PPARδ Overexpression or Activation Represses Stress-Induced Depressive Behaviors and Enhances Neurogenesis.

Background: Emerging data have demonstrated that peroxisome proliferator-activated receptor δ (PPARδ) activation confers a potentially neuroprotective role in some neurodegenerative diseases. However, whether PPARδ is involved in depression is unknown.

Methods: In this study, PPARδ was firstly investigated in the chronic mild stress (CMS) and learned helplessness (LH) models of depression.

Antidiabetic drugs restore abnormal transport of amyloid-β across the blood-brain barrier and memory impairment in db/db mice.

Previous studies have shown significant changes in amyloid-β (Aβ) transport across the blood-brain barrier (BBB) under diabetic conditions with hypoinsulinemia, which is involved in diabetes-associated cognitive impairment. Present study employed db/db mice with hyperinsulinemia to investigate changes in Aβ transport across the BBB, hippocampal synaptic plasticity, and restorative effects of antidiabetic drugs. Our results showed that db/db mice exhibited similar changes in Aβ transport across the BBB to that of insulin-deficient mice.

Pretreatment with antiasthmatic drug ibudilast ameliorates Aβ 1-42-induced memory impairment and neurotoxicity in mice.

Amyloid-β peptide (Aβ) is thought to be associated with the progressive neuronal death observed in Alzheimer's disease (AD). However, effective neuroprotective approaches against Aβ neurotoxicity are unavailable. Here, we investigated possible preventive effects of ibudilast, as a pharmacologic phosphodiesterase inhibitor, currently used for treatment of inflammatory diseases such as asthma, on Aβ 1-42-induced neuroinflammatory, apoptotic responses and memory impairment.

Montelukast rescues primary neurons against Aβ1-42-induced toxicity through inhibiting CysLT1R-mediated NF-κB signaling.

Amyloid-β peptide (Aβ), which can invoke a cascade of inflammatory responses, is considered to play a causal role in the development and progress of Alzheimer's disease (AD). Montelukast, known as a cysteinyl leukotriene receptor 1 (CysLT1R) antagonist, is currently used for treatment of inflammatory diseases such as asthma. We have previously reported that CysLT1R activation is involved in Aβ generation.

Telmisartan treatment ameliorates memory deficits in streptozotocin-induced diabetic mice via attenuating cerebral amyloidosis.

Telmisartan, an angiotensin II type 1-receptor blocker (ARBs), has been reported to exert beneficial effects on the central nervous system (CNS). However, the effect of telmisartan on cognitive impairment associated with type 1 diabetes is not well known. Here, we examined the possibility that telmisartan could improve memory function in a type 1 diabetic mouse model, streptozotocin (STZ)-induced diabetic mice.

Montelukast targeting the cysteinyl leukotriene receptor 1 ameliorates Aβ1-42-induced memory impairment and neuroinflammatory and apoptotic responses in mice.

Montelukast, known as a cysteinyl leukotriene receptor 1 (CysLT1R) antagonist, is currently used for treatment of inflammatory diseases such as asthma. Here, we investigated effects of montelukast on neuroinflammatory, apoptotic responses, and memory performance following intracerebral infusions of amyloid-β (Aβ). The data demonstrated that intracerebroventrical infusions of aggregated Aβ1-42 (410 pmol/mouse) produced deficits in learning ability and memory, as evidenced by increase in escape latency during acquisition trials and decreases in exploratory activities in the probe trial in Morris water maze (MWM) task, and by decrease in the number of correct choices and increase in latency to enter the shock-free compartment in Y-maze test, and caused significant increases in pro-inflammatory cytokines such as NF-κB p65, TNF-α and IL-1β as well as pro-apoptotic molecule caspase-3 activation and anti-apoptotic protein Bcl-2 downregulation in hippocampus and cortex.

Protective effect of pranlukast on Aβ₁₋₄₂-induced cognitive deficits associated with downregulation of cysteinyl leukotriene receptor 1.

Deposition of extracellular amyloid-β (Aβ) peptide is one of the pathological hallmarks of Alzheimer's disease (AD). Accumulation of Aβ is thought to associate with cognition deficits, neuroinflammation and apoptosis observed in AD. However, effective neuroprotective approaches against Aβ neurotoxicity are unavailable.

Fructus Gardenia Extract ameliorates oxonate-induced hyperuricemia with renal dysfunction in mice by regulating organic ion transporters and mOIT3.

The potent anti-hyperuricemia activities of Fructus Gardenia Extract (FGE) have been well reported. The aim of this study was to evaluate the uricosuric and nephro-protective effects of FGE and explore its possible mechanisms of action in oxonate-induced hyperuricemic mice. FGE was orally administered to hyperuricemic and normal mice for 1 week.

Leukotriene D4 induces cognitive impairment through enhancement of CysLT₁ R-mediated amyloid-β generation in mice.

Amyloid plaques in the extracellular parenchyma mainly consist of amyloid-β peptides (Aβ), one of the pathological hallmarks in Alzheimer's disease (AD). In the present study, we examined neuroinflammation, amyloidogenesis, and memory performance following intracerebral infusions of leukotriene D4 (LTD4) in mice. The results demonstrated that intracerebral infusions of LTD4 (1 ng/mouse) produced memory impairment as determined by Morris water maze test and Y-maze test in mice, and caused the accumulation of Aβ1-40 and Aβ1-42 in the hippocampus and cortex through increased activity of β- and γ-secretases accompanied with increased expression of amyloid precursor protein (APP).