1.Effects of light regulation on the synthesis of secondary metabolites in medicinal plants
Wei ZHANG ; Xiangqing MENG ; Xiaohui SU ; Jinyi WANG ; Lihua LI ; Min JIA
Journal of Pharmaceutical Practice and Service 2024;42(2):50-59
Secondary metabolites of medicinal plants are extremely important to human health because of their special pharmacological activities or efficacy. They are the main source of drugs, health care products, and cosmetics. As human beings continue to pursue health and longevity, the demand in the pharmaceutical market continues to grow. It becomes especially important to improve the production and quality of secondary metabolites of medicinal plants. Plant secondary metabolites are a kind of adaptation of plants to their environment and are the result of the interaction between plants and biotic and abiotic factors during the long-term evolution process. The production and accumulation of secondary metabolites in medicinal plants are mainly affected by plant genetic factors and environmental factors. Among them, light environment is extremely important for their synthesis. Therefore, light regulation has long been a research focus for many scholars in China and abroad. In this article, we the recent research progress on the effects of light regulation on the secondary metabolites of medicinal plants were reviewed, mainly focusing on the effects of light quality, light intensity and photoperiod, in order to provide theoretical basis and practical guidance for the efficient production of secondary metabolites with important pharmacological activities.
2.Basic and clinical research progress in carbon ion therapy for colorectal cancer
Xiangqing REN ; Tian HUANG ; Yuping WANG ; Zenan HU ; Yongning ZHOU
Chinese Journal of Radiation Oncology 2024;33(1):67-71
Colorectal cancer is a common clinical malignant tumor. As the main therapeutic method of colorectal cancer, radiotherapy has a good inhibitory effect on tumor progression. In recent years, because of its good physical and biological advantages, carbon ion has shown better clinical efficacy than traditional radiotherapy in the treatment of local recurrence or distant metastasis of colorectal cancer. In this article, basic and clinical studies related to the efficacy of carbon ion therapy for the recurrence of colorectal cancer in recent years were reviewed, aiming to provide theoretical basis for preventing and reducing adverse reactions after radiotherapy and prolonging the survival of colorectal cancer patients.
3.DING Yuanqing's Experience in Treating Young and Middle-Aged Post-Stroke Depression Patients with Regulating Qi and Promoting Blood Circulation Method
Chunyu HU ; Xuejun LI ; Jin WANG ; Saixue TANG ; Jiajing LI ; Cheng YU ; Xiangqing XU ;
Journal of Traditional Chinese Medicine 2024;65(19):1972-1977
This paper summarizes the experience of professor DING Yuanqing in treating post-stroke depression (PSD) of young and middle-aged patients with the method of regulating qi and promoting blood circulation. PSD is a syndrome resulting by vascular injury and impairment of brain marrow and vital activity after the stroke. Factors such as poor lifestyle, improper control of chronic diseases and sleep disorders,etc.,which can be harmful individually, or they can interact. Over time,these factors can block yang of defensive qi,obstract blood circulationg and disturb qi movement. Reverse ascending of defensive qi can generate wind and fire,generate phlegm and stasis from the fluid the blood. Qi stagnation, phlegm and stasis can combined with stagnation heat, phlegm heat, blood stasis heat which caused by stroke , which can further aggravate pulse accumulation, damage the blood vessels and block the collaterals. Consequently, defensive qi is floating over and nutrient qi is not smooth, resulting in inadequate nourishment of the brain marrow,and disfunction of vital activity, causing depressive symptoms. Professor DING innovatively applied the method of regulating qi and promoting blood circulation. He selected the classic prescriptions such as Guizhi Decoction(桂枝汤), Baoyuan Decoction(保元汤), as well as self-fitting prescriptions like Erdan Decoction(二丹汤), Erzhu Decoction(二竹汤), to relieve qi and tonify qi,promote harmonious blood circulation, facilitate vasodilation, ease symptoms of depression, invigorate the mind, and provide an effective treatment for PSD.
4.Relationship between epilepsy and patent foramen ovale
Xu ZHANG ; Chenjing SHAO ; Desheng LI ; Ran AO ; Xiaobing SHI ; Xiangqing WANG
Chinese Journal of Internal Medicine 2024;63(10):993-995
This study aimed to investigate the prevalence and clinical characteristics of epilepsy in patients with patent foramen ovale (PFO) and the effect of PFO closure on seizures. Patients diagnosed with PFO were recruited and underwent brain magnetic resonance imaging, electrocardiography, transesophageal echocardiography, and transthoracic echocardiography with right ventriculography. In patients with epilepsy, electroencephalography was performed. A total of 110 patients completed the assessment. A chief complaint of chest tightness or palpitations was proportionately higher in patients aged<18 years, whereas headaches and seizures were higher in patients aged≥18 years ( χ2=4.69 ,P<0.05). Comorbid epilepsy was observed in 20.9% of patients with PFO. The age at admission in the epileptic group (14-66(27±14)years) was significantly lower than that in the non-epileptic group (16-81(38±21)years) and that in patients with headache as the chief complaint (16-68(39±12)years) ( t=3.29, P<0.05). The multivariate analysis found no risk factors related to the prognosis of epilepsy. The incidence of epilepsy was significantly higher in patients with PFO than in the general population.
5.Progress in the clinical application of the biased μ-opioid agonist olic-eridine
Changmao ZHU ; Li XIE ; Zifeng WU ; Sen WANG ; Qi ZHANG ; Xiangqing XU ; Chun YANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(9):1057-1061
Opioid receptors μOR,δOR,κOR and NOPR are all G protein-coupled receptors(GPCRs),which mainly function through G protein and β-ar-restin.Recent studies have found that G protein mediates analgesia,while β-arrestin reduces anal-gesia and is related to the side effects of opioids.Oliceridine is the first biased μOR agonist approved for commerce.It mainly exerts analgesic effect by activating G protein.It has rapid onset of action and reliable analgesic effect.Due to its low activity on β-arrestin,the incidence of side effects is low,comparing to the classic opioid morphine.Oliceri-dine can be safely used in patients with liver or kid-ney insufficiency and its metabolite is inactive.This article summarizes the current progress of pharma-cological research and clinical application of oliceri-dine,aiming to provide reference for the clinical practice of oliceridine.
6.Clinical characteristics of patients with elderly-onset epilepsy and influencing factors for medication efficacy
Xu ZHANG ; Feng XIANG ; Xiaobing SHI ; Yang LI ; Xiaoyang LAN ; Shimin ZHANG ; Senyang LANG ; Xiangqing WANG
Chinese Journal of Neuromedicine 2024;23(7):692-697
Objective:To analyze the clinical characteristics and medication options of patients with elderly-onset epilepsy and influencing factors for medication efficacy.Methods:A total of 213 patients with elderly-onset epilepsy (age of onset≥65 years) were selected from Epilepsy Outpatient, Department of Neurology, First Medical Center of Chinese PLA General Hospital from February 1999 to March 2023. General data, imaging findings and follow-up results of these patients were collected. Seizure frequencies and types, medication types, and medication efficacy were analyzed retrospectively. According to medication efficacy, these patients were divided into effective anti-seizure medications (ASMs) group and ineffective ASMs group (effective ASMs was defined as having no seizures or seizure reduction>50% at 6 months after medication, and ineffective ASMs as having seizure reduction≤50% or seizure increase. Univariate and multivariate Logistic regression analyses were used to identify the influencing factor for ASMs efficacy.Results:In these 213 patients with elderly-onset epilepsy, 143 (67.1%) were males and 70 (32.9%) were females. Onset age was 70.0 (67.0, 74.5) years, with duration of 12 (4, 32) months. Time from first onset to treatment was 2.0 (1.0, 10.5) months, with that<2 months enjoying the largest proportion ( n=101). MRI/CT in 102 patients indicated potential epileptogenic abnormal structures, such as post-stroke gliosis/encephalomalacia ( n=67) and post-traumatic gliosis/encephalomalacia ( n=13). MRI/CT in 78 patients indicated non-epileptogenic abnormal structures, such as ischemic changes of small and medium vessels ( n=51) and brain atrophy ( n=15). Structural change was the most common cause ( n=160). Sixty-nine patients (32.4%) did not take medicine and 144 (67.6%) took medicine at the visiting; sodium valproate was mostly used ( n=74), followed by levetiracetam ( n=35) and carbamazepine ( n=24). Five patients had sodium valproate combined with levetiracetam, and 4 patients had sodium valproate combined with carbamazepine. Multivariate Logistic regression analysis showed that disease duration and medication combination were independent influencing factors for ASMs efficacy. Conclusion:Structural change is the main cause for elderly-onset epilepsy; medication efficacy is worse in patients with longer disease course and medication combination therapy.
7.Clinical and Structural Characteristics of NEU1 Variants Causing Sialidosis Type 1
Yingji LI ; Yang LIU ; Rongfei WANG ; Ran AO ; Feng XIANG ; Xu ZHANG ; Xiangqing WANG ; Shengyuan YU
Journal of Movement Disorders 2024;17(3):282-293
Objective:
Sialidosis type 2 has variants that are both catalytically inactive (severe), while sialidosis type 1 has at least one catalytically active (mild) variant. This study aimed to discuss the structural changes associated with these variants in a newly reported family carrying N-acetyl-α-neuraminidase-1 (NEU1) variants and explore the clinical characteristics of different combinations of variants in sialidosis type 1.
Methods:
First, whole-exome sequencing and detailed clinical examinations were performed on the family. Second, structural analyses, including assessments of energy, flexibility and polar contacts, were conducted for several NEU1 variants, and a sialidase activity assay was performed. Third, previous NEU1 variants were systematically reviewed, and the clinical characteristics of patients in the severe-mild and mild-mild groups with sialidosis type 1 were analyzed.
Results:
We report a novel family with sialidosis type 1 and the compound heterozygous variants S182G and V143E. The newly identified V143E variant was predicted to be a mild variant through structural analysis and was confirmed by a sialidase activity assay. Cherry-red spots were more prevalent in the severe-mild group, and ataxia was more common in the mild-mild group. Impaired cognition was found only in the severe-mild group. Moreover, patients with cherry-red spots and abnormal electroencephalographies and visual evoked potentials had a relatively early age of onset, whereas patients with myoclonus had a late onset.
Conclusion
Changes in flexibility and local polar contacts may be indicators of NEU1 pathogenicity. Sialidosis type 1 can be divided into two subgroups according to the variant combinations, and patients with these two subtypes have different clinical characteristics.
8.Carbazole and tetrahydro-carboline derivatives as dopamine D3 receptor antagonists with the multiple antipsychotic-like properties.
Zhongtang LI ; Fan FANG ; Yiyan LI ; Xuehui LV ; Ruqiu ZHENG ; Peili JIAO ; Yuxi WANG ; Guiwang ZHU ; Zefang JIN ; Xiangqing XU ; Yinli QIU ; Guisen ZHANG ; Zhongjun LI ; Zhenming LIU ; Liangren ZHANG
Acta Pharmaceutica Sinica B 2023;13(11):4553-4577
Dopamine D3 receptor (D3R) is implicated in multiple psychotic symptoms. Increasing the D3R selectivity over dopamine D2 receptor (D2R) would facilitate the antipsychotic treatments. Herein, novel carbazole and tetrahydro-carboline derivatives were reported as D3R selective ligands. Through a structure-based virtual screen, ZLG-25 (D3R Ki = 685 nmol/L; D2R Ki > 10,000 nmol/L) was identified as a novel D3R selective bitopic ligand with a carbazole scaffold. Scaffolds hopping led to the discovery of novel D3R-selective analogs with tetrahydro-β-carboline or tetrahydro-γ-carboline core. Further functional studies showed that most derivatives acted as hD3R-selective antagonists. Several lead compounds could dose-dependently inhibit the MK-801-induced hyperactivity. Additional investigation revealed that 23j and 36b could decrease the apomorphine-induced climbing without cataleptic reaction. Furthermore, 36b demonstrated unusual antidepressant-like activity in the forced swimming tests and the tail suspension tests, and alleviated the MK-801-induced disruption of novel object recognition in mice. Additionally, preliminary studies confirmed the favorable PK/PD profiles, no weight gain and limited serum prolactin levels in mice. These results revealed that 36b provided potential opportunities to new antipsychotic drugs with the multiple antipsychotic-like properties.
9.Electroacupuncture alleviates orofacial allo-dynia and anxiety-like behaviors by regulating synaptic plasticity of the CA1 hippocampal region in a mouse model of trigeminal neuralgia
Yuzhi JIA ; Haitao LI ; Guangming ZHANG ; Hongyun WU ; Sishuo ZHANG ; Hongwei ZHI ; Yahan WANG ; Jingwen ZHU ; Yifan WANG ; Xiangqing XU ; Caijun TIAN ; Wenqiang CUI
Chinese Journal of Pharmacology and Toxicology 2023;37(z1):69-70
OBJECTIVE To investigate whether electroacupuncture(EA)ameliorates abnormal trigeminal neuralgia(TN)orofacial pain and anxiety-like behavior by altering synaptic plasticity in the hippocampus CA1.METHODS A mouse infraorbital nerve transection model(pT-ION)of neuropathic pain was established,and EA or sham EA was used to treat ipsilateral acu-puncture points(GV20-Baihui and ST7-Xia-guan).Golgi-Cox staining and transmission elec-tron microscopy(TEM)were administrated to observe the changes of synaptic plasticity in the hippocampus CA1.RESULTS Stable and per-sistent orofacial allodynia and anxiety-like behav-iors induced by pT-ION were related to changes in hippocampal synaptic plasticity.Golgi stain-ings showed a decrease in the density of dendritic spines,especially mushroom-type dendritic spines,in hippocampal CA1 neurons of pT-ION mice.TEM results showed that the density of synapses,membrane thickness of the postsynap-tic density,and length of the synaptic active zone were decreased,whereas the width of the synap-tic cleft was increased in pTION mice.EA attenu-ated pT-ION-induced orofacial allodynia and anx-iety-like behaviors and effectively reversed the abnormal changes in dendritic spines and syn-apse of the hippocampal CA1 region.CONCLU-SION EA modulates synaptic plasticity of hippo-campal CA1 neurons,and reduces abnormal oro-facial pain and anxiety-like behavior,providing evidence for a TN treatment strategy.
10.Anti-tumor mechanism study on saffron by network pharmacology and reverse molecular docking
Xiangqing MENG ; Lihua LI ; Hongrui WANG ; Dan JIA ; Min JIA
Journal of Pharmaceutical Practice 2023;41(3):160-167
Objective To explore the anti-tumor mechanism of saffron (Crocus sativus L.) by network pharmacology and reverse molecular docking techniques. Methods The main chemical components of saffron were obtained by searching published literature and TCMSP database. The potential targets of these components were predicted using PharmMapper server. The corresponding target genes were identified from UniProt database. The underlying anti-tumor targets of saffron were obtained by mapping the disease genes of cancer or tumor with GeneCards, OMIM and TTD databases. Cytoscape software was used to construct the action target network of saffron active components. The protein-protein interaction analysis was performed by String database, and the GO function and KEGG pathway enrichment analysis were performed by Metascape platform. Finally, molecular docking was performed to evaluate the binding of main components with their potential targets. Results A total of 9 active ingredients in saffron including quercetin, kaempferol, isorhamnetin, picrocrocin and crocin I, were identified, which might act on 37 key targets including AKT1, CCND1, MMP9, EGFR, TP53, involved in P53, TNF and other signaling pathways. Molecular docking indicated modest binding potency through hydrogen bonding, and hydrophobic interactions. Conclusion The anti-tumor effect of saffron was evaluated via the network of components-targets-pathways, which might provide a foundation for further research.

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