Oxidative Stress and Antioxidative Therapy in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is clinically characterized by a progressive increase in pulmonary artery pressure, followed by right ventricular hypertrophy and subsequently right heart failure. The underlying mechanism of PAH includes endothelial dysfunction and intimal smooth muscle proliferation. Numerous studies have shown that oxidative stress is critical in the pathophysiology of PAH and involves changes in reactive oxygen species (ROS), reactive nitrogen (RNS), and nitric oxide (NO) signaling pathways.

The Mechanism, Clinical Efficacy, Safety, and Dosage Regimen of Atomoxetine for ADHD Therapy in Children: A Narrative Review.

Atomoxetine, a selective norepinephrine (NE) reuptake inhibitor, was approved for attention deficit/hyperactivity disorder (ADHD) treatment in children, adolescents and adults. We searched the database PubMed/MEDLINE (2000 to October 1, 2021). Only publications in English were considered.

Vincristine-Induced Peripheral Neuropathy in Childhood Acute Lymphoblastic Leukemia: Genetic Variation as a Potential Risk Factor.

Vincristine (VCR) is the first-line chemotherapeutic medication often co-administered with other drugs to treat childhood acute lymphoblastic leukemia. Dose-dependent neurotoxicity is the main factor restricting VCR's clinical application. VCR-induced peripheral neuropathy (VIPN) sometimes results in dose reduction or omission, leading to clinical complications or affecting the patient's quality of life.

CaMKII and Ca3.2 T-type calcium channel mediate Connexin-43-dependent inflammation by activating astrocytes in vincristine-induced neuropathic pain.

Vincristine (VCR), an alkaloid isolated from vinca, is a commonly used chemotherapeutic drug. However, VCR therapy can lead to dose-dependent peripheral neurotoxicity, mainly manifesting as neuropathic pain, which is one of the dominant reasons for limiting its utility. Experimentally, we discovered that VCR-induced neuropathic pain (VINP) was accompanied by astrocyte activation; the upregulation of phospho-CaMKII (p-CaMKII), Ca3.

Dose tailoring of tacrolimus based on a non-linear pharmacokinetic model in children with refractory nephrotic syndrome.

The population pharmacokinetics (PPK) of tacrolimus (TAC) in children with refractory nephrotic syndrome (RNS) have not been well-characterized. This study aimed to investigate the significant factors affecting the TAC PPK characteristics of children with RNS and to optimize the dosing regimen. A total of 494 concentrations from 108 children were obtained from routine therapeutic drug monitoring between 2016 and 2018.

Vincristine-induced peripheral neuropathy: A mini-review.

Vincristine (VCR), an alkaloid extracted from vinca, is often used in combination with other chemotherapeutic drugs to treat a variety of cancers, such as acute lymphoblastic leukaemia (ALL), malignant lymphoma, and neuroblastoma. However, VCR possesses dose-dependent neurotoxicity, which is the main factor restricting its application. Vincristine-induced peripheral neuropathy (VIPN) not only limits the dose of VCR and leads to the discontinuation of treatment but also triggers serious damage to the physical and mental health of patients.

XQ-1H regulates Wnt/GSK3β/β-catenin pathway and ameliorates the integrity of blood brain barrier in mice with acute ischemic stroke.

10-O-(N, N-dimethylaminoethyl) ginkgolide B methanesulfonate (XQ-1H), a novel analog of ginkgolide B, has been preliminarily recognized to show bioactivities against ischemia-induced injury. However, the underlying mechanism still remains to be fully elucidated. The aim of this study was to investigate the effect of XQ-1H against cerebral ischemia/reperfusion injury (CIRI) from the perspective of blood brain barrier (BBB) protection, and explore whether the underlying mechanism is associated with Wnt/GSK3β/β-catenin signaling pathway activation.

Ma Xing Shi Gan Decoction Protects against PM2.5-Induced Lung Injury through Suppression of Epithelial-to-Mesenchymal Transition (EMT) and Epithelial Barrier Disruption.

This research was designed to explore the effect of Ma Xing Shi Gan decoction (MXD) in alleviating particulate matter less than 2.5 m in diameter (PM2.5) induced lung injury from the perspective of epithelial barrier protection and inhibition of epithelial-to-mesenchymal transition (EMT).

Discovery of 1,6-naphthyridinone-based MET kinase inhibitor bearing quinoline moiety as promising antitumor drug candidate.

A series of 1,6-naphthyridinone-based MET kinase inhibitors bearing quinoline moiety in block A were designed and synthesized based on the structures of Cabozantinib and our reported compound IV. Extensive SAR and DMPK studies led to the identification of 20j, a potent and orally bioavailable MET kinase inhibitor with favorable kinase selectivity. More importantly, 20j exhibited statistically significant tumor growth inhibition (Tumor growth inhibition/TGI of 131%, 4/6 partial regression/PR) in the U-87 MG xeograft model, which is superior to that of Cabozantinib (TGI of 97%, 2/6 PR), and significantly better than that of compound IV (TGI of 15%, 0/6 PR) at the same dose (12.

Ma Xing Shi Gan Decoction Attenuates PM2.5 Induced Lung Injury via Inhibiting HMGB1/TLR4/NFκB Signal Pathway in Rat.

Ma Xing Shi Gan Decoction (MXD), a classical traditional Chinese medicine prescription, is widely used for the treatment of upper respiratory tract infection. However, the effect of MXD against particulate matters with diameter of less than 2.5 μm (PM2.

Research Progress of Mechanisms and Drug Therapy For Atherosclerosis on Toll-Like Receptor Pathway.

Recent reports have established atherosclerosis (AS) as a major factor in the pathogenetic process of cardiovascular diseases such as ischemic stroke and coronary heart disease. Although the possible pathogenesis of AS remains to be elucidated, a large number of investigations strongly suggest that the inhibition of toll-like receptors (TLRs) alleviates the severity of AS to some extent by suppressing vascular inflammation and the formation of atherosclerotic plaques. As pattern recognition receptors, TLRs occupy a vital position in innate immunity, mediating various signaling pathways in infective and sterile inflammation.

JLX001 Ameliorates Ischemia/Reperfusion Injury by Reducing Neuronal Apoptosis via Down-Regulating JNK Signaling Pathway.

JLX001, a novel compound with similar structure with cyclovirobuxine D (CVB-D), has been proved to exert therapeutical effects on permanent focal cerebral ischemia. However, the protective effects of JLX001 on cerebral ischemia/reperfusion (I/R) injury and its anti-apoptotic effects have not been reported. We investigated the efficacy of JLX001 in two pharmacodynamic tests (pre-treatment test and post-treatment) with rats subjected to middle cerebral artery occlusion/reperfusion (MCAO/R).

Therapeutic effects of JLX-001 on ischemic stroke by inducing autophagy via AMPK-ULK1 signaling pathway in rats.

(3β,5α,16α,20S)-4,4,14-trimethyl-3,20-bis(methylamino)-9,19-cyclopregnan-16-ol-dihydrochloride (JLX-001), a structural analogue of cyclovirobuxine D (CVB-D), is a novel compound from synthesis. This study aims to confirm the therapeutic effects of JLX001 on ischemic stroke (IS) and research its induction of autophagy function via 5'-AMP-activated protein kinase (AMPK)-Human Serine/threonine-protein kinase (ULK1) signaling pathway activation. The therapeutic effects of JLX001 were evaluated by infarct sizes, brain edema, neurological scores and proportion of apoptotic neurons in Sprague-Dawley (SD) rats with middle cerebral artery occlusion/reperfusion (MCAO/R).

Correction: Anti-ulcerogenic effect of KFP-H008 against ethanol-induced gastric ulcer p38 MAPK/NF-κB pathway.

[This corrects the article DOI: 10.1039/C7RA08879E.].

Immune Cells After Ischemic Stroke Onset: Roles, Migration, and Target Intervention.

Ischemic stroke is one of the leading health issues and the major cause of permanent disability in adults worldwide. Energy depletion and hypoxia occurring after ischemic stroke result in cell death, which activates resident glia cells and promotes the peripheral immune cells breaching into brain performing various functions even contradictory effects. The infiltration of immune cells may mediate neuron apoptosis and escalate ischemic damage, while it enhances neuron repair, differentiation, and neuroregeneration.

Berberine attenuates ischemia-reperfusion injury through inhibiting HMGB1 release and NF-κB nuclear translocation.

Inflammatory damage plays an important role in cerebral ischemic pathogenesis and represents a new target for treatment of stroke. Berberine is a natural medicine with multiple beneficial biological activities. In this study, we explored the mechanisms underlying the neuroprotective action of berberine in mice subjected transient middle cerebral artery occlusion (tMCAO).

Therapeutic effects of JLX001 on cerebral ischemia through inhibiting platelet activation and thrombus formation in rats.

(3β,5α,16α,20S)-4,4,14-trimethyl-3,20-bis(methylamino)-9,19-cyclopregnan-16-ol-dihydrochloride (JLX001), a derivative of cyclovirobuxine D (CVB-D), is a novel compound from synthesis. This study aims to confirm the therapeutic effect of JLX001 on cerebral ischemia and researchits antiplatelet and antithrombosis activities via thromboxane (TXA)/phospholipase C-β-3(PLCβ3)/protein kinase C (PKC) pathway suppression. The therapeutic effects of JLX001 was evaluated by infarct sizes, brain edema and neurological scores in Sprague-Dawley (SD) rats with middle cerebral artery occlusion (MCAO).

Research progress of mechanisms and drug therapy for neuropathic pain.

Neuropathic pain is maladaptive pain caused by injury or dysfunction in peripheral and central nervous system, and remains a worldwide thorny problem leading to decreases in physical and mental quality of people's life. Currently, drug therapy is the main treatment regimen for resolving pain, while effective drugs are still unmet in medical need, and commonly used drugs such as anticonvulsants and antidepressants often make patients experience adverse drug reactions like dizziness, somnolence, severe headache, and high blood pressure. Thus, in this review we overview the anatomical physiology, underlying mechanisms of neuropathic pain to provide a better understanding in the initiation, development, maintenance, and modulation of this pervasive disease, and inspire research in the unclear mechanisms as well as potential targets.

Salvia miltiorrhiza Bunge (Danshen) extract attenuates permanent cerebral ischemia through inhibiting platelet activation in rats.

Ethnopharmacological Relevance: Danshen is a crude herbal drug isolated from dried roots of Salvia miltiorrhiza Bunge. This plant is widely used in oriental medicine for the treatment of cardiovascular and cerebrovascular diseases. The supercritical CO extract from Danshen (SCED) (57.

KFP-H008 blocks gastric acid secretion through inhibiting H-K-ATPase.

1-(5-(1H-indol-5-yl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine (KFP-H008)，a novel and potent potassium-competitive acid blocker for the treatment of acid secretion related diseases, has not been reported previously. In this study, we demonstrated that KFP-H008 inhibits basal acid secretion, 2-deoxy-D-glucose- (2DG-) stimulated gastric acid secretion in rats. KFP-H008 blocked histamine-stimulated acid secretion in rats and heidenhain pouch dogs and reversed acid output in isolated gastric perfusion under histamine stimulation.

Daphnetin Alleviates Experimental Autoimmune Encephalomyelitis via Regulating Dendritic Cell Activity.

Aims: Daphnetin, a coumarin derivative extracted from Daphne odora var. marginata, has been reported to have antiinflammatory and immunosuppressive properties. Our previous study indicated that it was able to remarkably suppress the neuroinflammation and suggested its potential application in treating neuroinflammatory diseases.

[Inhibitory effects and mechanisms of snake venom tripeptide pENW on platelet adhesion].

This study was designed to investigate inhibitory effects and possible mechanisms of snake venom tripeptide (pENW) on platelet adhesion in order to promote the development of a novel anti-platelet therapy. To study the inhibitory effects of pENW on platelet adhesion, washed platelets pre-incubated with pENW (116.5-466.

The molecular insight into the antihyperuricemic and renoprotective effect of Shuang Qi gout capsule in mice.

Ethnopharmacological Relevance: Shuang-Qi gout capsule, a traditional Chinese medicine prescription, has been used in the treatment of, gout arthritis, arthralgia and inflammation. Since renal urate overload associated with severe disability including gout, elimination of excess renal uric acid is highly essential. Therefore, in this study we evaluated the antihyperuricemic and the renoprotective effect of the Shuang Qi gout capsule (SQ) with elucidation of its mechanism.

Clematichinenoside AR induces immunosuppression involving Treg cells in Peyer׳s patches of rats with adjuvant induced arthritis.

Ethnopharmacological Relevance: Clematichinenoside AR (AR) has been defined as a major active ingredient of triterpenoid saponins extracted from Clematidis Radix et Rhizoma, which is a traditional Chinese herbal medicine that has long been used in the treatment of rheumatoid arthritis (RA). To further explore the mechanism of AR in the treatment of RA, we investigated whether its immunomodulatory effects are related to Treg-mediated suppression derived from Peyer׳s patches (PPs) in adjuvant induced arthritis (AIA) rat model.

Materials And Methods: AR (8, 16, 32 mg/kg) was orally administered daily from Day 18 to Day 31 after immunization.

Anti-inflammatory and antinociceptive effects of Chinese medicine SQ gout capsules and its modulation of pro-inflammatory cytokines focusing on gout arthritis.

Ethnopharmacological Relevance: Shuang-Qi gout capsule is a traditional Chinese medicine prescription, which has been used in the treatment of joint pain, inflammation and gout arthritis. This study evaluates anti-inflammatory and antinociceptive effects of Shuang-Qi gout capsule and its modulation of pro-inflammatory cytokines with special reference to gout arthritis.

Materials And Methods: Anti-inflammatory effect of Shuang-Qi gout capsule was investigated bymice tail-flick response, acetic acid induced writhing response, Xylene-induced auricle inflammation and the hind paw volume of the monosodium urate (MSU) crystal induced rats with different time durations.