Therapeutic Strategies for Postherpetic Neuralgia: Mechanisms, Treatments, and Perspectives.

PURPOSE OF REVIEW: Postherpetic neuralgia is an annoying pain that mainly affects older people. In order to give patients more options, this review summarizes the pharmacological and interventional treatments for postherpetic neuralgia and updates the research on the efficacy, thereby providing doctors with more treatment options. The adverse effects and effective doses of its various treatments are also presented so that the therapy can be prescribed according to their concrete physical conditions. In a word, this review is dedicated to providing a comprehensive overview of the treatment options for postherpetic neuralgia and offering patients more choices. RECENT FINDINGS: Combinational therapy is more excellent than monotherapy. The local anesthesia and gabapentin comprised outstanding compatibility. In addition, two therapeutic tools for PHN patients, especially for the intractable ones, electroacupuncture (EA), and osteopathic manipulative treatment (OMT), show their efficacy and become potential options to alleviate pain. In terms of treatment, guidelines recommend patients use tricyclic antidepressants (TCAs), gabapentin, pregabalin, and 5% lidocaine patches as the first-line medications, and gabapentin is investigated most, especially the gabapentin enacarbil (GEn). And drug efficacy can be limited by adverse effects and tolerated doses. Interventional treatments, with their invasiveness and operational difficulty, are usually considered for intractable patients. Combinational therapies may be used when a single therapy cannot achieve the desired effect. Therapies such as OMT and EA have also been proposed to palliate pain in some cases, and future directions of treatment may be investigated in Chinese medicine and acupuncture.

Network Pharmacology and Molecular Docking Analysis on Molecular Targets and Mechanisms of Fei Jin Sheng Formula in the Treatment of Lung Cancer.

BACKGROUND: Fei Jin Sheng Formula (FJSF) is widely used in clinical treatment of lung cancer. But the underlying active ingredients and mechanisms are unclear. OBJECTIVE: To investigate the active components and functional mechanisms of FJSF in treating lung cancer using a network pharmacology approach and molecular docking combined with vitro experiments Methods: Based on the TCMSP and related literature, the chemical components of related herbs in FJSF were collected. The active components of FJSF were screened by ADME parameters, and the targets were predicted by the Swiss Target Prediction database. The "drug-active ingredient-target" network was constructed by Cytoscape. Disease-related targets of lung cancer were acquired from GeneCards, OMIM, and TTD databases. Then drug-disease intersection target genes were obtained through the Venn tool. GO analysis and KEGG pathway enrichment analysis were performed via the Metascape database. Cytoscape was used to construct a PPI network and perform topological analysis. Kaplan-Meier Plotter was used to analyze the relationship between DVL2 and the prognosis of lung cancer patients. xCell method was used to estimate the relationship between DVL2 and immune cell infiltration in lung cancer. Molecular docking was performed by AutoDockTools-1.5.6. The results were verified by experiments in vitro. RESULTS: FJSF contained 272 active ingredients and 52 potential targets for lung cancer. GO enrichment analysis is mainly related to cell migration and movement, lipid metabolism, and protein kinase activity. KEGG pathway enrichment analysis mainly involves PI3K-Akt, TNF, HIF-1, and other pathways. Molecular docking shows that the compound Xambioona, quercetin and methyl palmitate in FJSF has a strong binding ability with NTRK1, APC, and DVL2. Analysis of the data in UCSC to analyze the expression of DVL2 in lung cancer shows that DVL2 was overexpressed in lung adenocarcinoma tissues. Kaplan-Meier analysis shows that the higher DVL2 expression in lung cancer patients was associated with poorer overall survival and poorer survival in stage I patients. It was negatively correlated with the infiltration of various immune cells in the lung cancer microenvironment. Vitro Experiment showed that Methyl Palmitate (MP) can inhibit the proliferation, migration, and invasion of lung cancer cells, and its mechanism of action may be to downregulate the expression of DVL2. CONCLUSION: FJSF may play a role in inhibiting the occurrence and development of lung cancer by downregulating the expression of DVL2 in A549 cells through its active ingredient Methyl Palmitate. These results provide scientific evidence for further investigations into the role of FJSF and Methyl Palmitate in the treatment of lung cancer.

Leaves, seeds and exocarp of Ginkgo biloba L. (Ginkgoaceae): A Comprehensive Review of Traditional Uses, phytochemistry, pharmacology, resource utilization and toxicity.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba L. (Ginkgoaceae) is a treasure species with high medicinal value. The Ming Dynasty "Compendium of Materia Medica" and Qing Dynasty "Bencao Fengyuan" in China recorded this herbal medicine can reduce phlegm, clear poison, treat diarrhea and frequent urination, etc. AIM OF THE STUDY: Until now, there is no painstakingly summarized review on leaves, seeds and exocarp of G. biloba simultaneously. This review will systematically summarize and compare current knowledge of G. biloba. MATERIALS AND METHODS: Ample original publications related to traditional uses, phytochemistry, pharmacology, resource utilization and toxicity of G. biloba leaves, seeds and exocarp till the end of 2021 were searched and collected by using various literature databases, including China National Knowledge Infrastructure, PubMed, Elsevier, Springer, Google Scholar and Web of Science database. RESULTS: According to classical Chinese herbal books and Chinese Pharmacopoeia, relieving cough, reducing phlegm, clearing poison and relieving diarrhea are the main pharmacological effects of G. biloba. The common chemical ingredients in different parts of G. biloba are flavonoids, terpenoids, phenolic acids, polysaccharides and endotoxin, etc. Among them, flavonoids and terpenoids are the main bioactive compounds in G. biloba leaves. Phenolic acids are the main bioactive compounds in G. biloba exocarp. G. biloba seeds are rich in nutritional ingredients, such as starch, adipose, protein, etc. Modern pharmacological studies showed that the crude extracts or compounds of G. biloba leaves, seeds and exocarp can be used for treating cardiovascular and cerebrovascular diseases, Alzheimer's disease, atherosclerosis, cancer, asthma, non-alcoholic fatty liver, diabetic complications and other diseases. In daily life, G. biloba seeds were usually used as raw material or additives for commodities, healthy food, drinks, even insecticides and antibacterial agents, etc. G. biloba leaves and seeds have been mainly applied for treating cardiovascular and cerebrovascular diseases, cough and asthma in clinical. However, endotoxins and ginkgolic acids have been identified as the dominating toxic ingredients in different parts of G. biloba. Besides, flavonoids and ginkgolides also have been proved to have toxicity recently. CONCLUSIONS: This review systematically sums up and compares the traditional uses, phytochemistry, pharmacology, resource utilization and toxicity research progress of G. biloba leaves, seeds and exocarp for the first time. It will provide some comprehensive reference data and suggestions for future research on this herbal medicine.

Tris(1,3-dichloro-2-propyl)phosphate Reduces the Lifespan via Activation of an Unconventional Insulin/Insulin-Like Growth Factor-1 Signaling Pathway.

Tris(1,3-dichloro-2-propyl)phosphate (TDCPP) is an environmental contaminant that has attracted increasing concern due to its presence in environmental media and biological samples. Our previous study demonstrated that exposure to TDCPP reduced the lifespan of Caenorhabditis elegans, but the mechanisms, including the relevant signaling pathways, are unclear. The current study found that TDCPP exposure triggers an unconventional insulin/insulin-like growth factor signaling (IIS) pathway, not by disrupting the insulin-like growth factor-1 receptor DAF-2/IGF1R but by inhibiting the downstream tumor-suppressor factor DAF-18/PTEN. This inhibition reduces PI(3,4,5)P3 (PIP3) dephosphorylation, causing buildup that increases the activation of the Akt/Protein Kinase B (PKB) family of serine/threonine kinases. This activation induces DAF-16/FoxO phosphorylation and promotes the sequestration of DAF-16/FoxO in the cytoplasm, reducing the lifespan of nematodes. Our results have important diagnostic and therapeutic implications for controlling TDCPP-related diseases, especially those originating with IIS pathway components.

[Mechanism study on leptin resistance in lung cancer cachexia rats treated by Xiaoyan Decoction].

OBJECTIVE: To study the leptin resistance mechanism of Xiaoyan Decoction (XD) in lung cancer cachexia (LCC) rats. METHODS: An LCC rat model was established. Totally 40 rats were randomly divided into the normal control group, the LCC model group, the XD group, and the positive control group, 10 in each group. After LCC model was set up, rats in the LCC model group were administered with normal saline, 2 mL each time. Rats in the XD group were administered with XD at the daily dose of 2 mL. Those in the positive control group were administered with Medroxyprogesterone Acetate suspension (20 mg/kg) by gastrogavage at the daily dose of 2 mL. All medication lasted for 14 days. The general condition and tumor growth were observed. Serum levels of leptin and leptin receptor in the hypothalamus were detected using enzyme-linked immunosorbent assay. Contents of neuropeptide Y (NPY) and anorexia for genomic POMC were detected using real-time PCR technique. RESULTS: Serum leptin levels were lower in the LCC model group than in the normal control group with statistical significance (P < 0.05). Compared with the LCC model groups, serum leptin levels significantly increased in the XD group (P < 0.01). Leptin receptor levels in the hypothalamus increased significantly in the LCC model group (P < 0.01). Increased receptor levels in the LCC model group indicated that either XD or Medroxyprogesterone Acetate could effectively reduce levels of leptin receptor with statistical significance (P < 0.01). There was also statistical difference between the XD group and the positive control group (P < 0.05). Contents of NPY was higher in the LCC model group than in the other groups with statistical difference (P < 0.05). There was no statistical difference in NPY between the normal control group and the rest 2 treatment groups (P > 0.05). There was statistical difference in POMC between the normal control group and the LCC model group (P < 0.05). POMC could be decreased in the XD group and the positive control group with statistical significance (P < 0.05), and it was more obviously decreased in the XD group (P < 0.05). CONCLUSIONS: Leptin resistance existed in LCC rats. XD could increase serum leptin levels and reduce leptin receptor levels in the hypothalamus. LCC could be improved by elevating NPY contents in the hypothalamus and reducing POMC contents, promoting the appetite, and increasing food intake from the periphery pathway and the central pathway.