Calcium ions (Ca2+) play a vital role in many biological processes. Transmembrane and coiled-coil domain 1 (TMCO1) has been characterized as an endoplasmic reticulum (ER) transmembrane protein in recent years. It keeps the cytoplasm and ER's Ca2+ homeostasis stable by acting as a novel calcium channel. Studies from different laboratories have revealed that the mutation or deficiency of TMCO1 is closely correlated with several diseases, including cerebro-facio-thoracic dysplasia (CFTD), glaucoma, premature ovarian failure (POF), osteoporosis, and cancer. Here, we review the characteristics of TMCO1 and its involvement in related diseases, which may provide useful information for developing therapeutic strategies for these diseases, as well as promote further research on this protein.

The molecular chaperone heat shock protein 90 (HSP90) regulates multiple crucial signalling pathways in cancer by driving the maturation of key signalling components, thereby playing a crucial role in tumorigenesis and drug resistance in cancer. Inhibition of HSP90 results in metastable conformational collapse of its client proteins and their proteasomal degradation. Considerable efforts have been devoted to the development of small-molecule inhibitors targeting HSP90, and more than 20 inhibitors have been evaluated in clinical trials for cancer therapy. However, owing to disadvantages such as organ toxicity and drug resistance, only one HSP90 inhibitor has been approved for use in clinical settings. In recent years, HSP90 inhibitors used in combination with other anti-cancer therapies have shown remarkable potential in the treatment of cancer. HSP90 inhibitors work synergistically with various anti-cancer therapies, including chemotherapy, targeted therapy, radiation therapy and immunotherapy. HSP90 inhibitors can improve the pharmacological effects of the above-mentioned therapies and reduce treatment resistance. This review provides an overview of the use of combination therapy with HSP90 inhibitors and other anti-cancer therapies in clinical and preclinical studies reported in the past decade and summarises design strategies and prospects for these combination therapies. Altogether, this review provides a theoretical basis for further research and application of these combination therapies in the treatment of cancer.

Traditional Chinese medicine (TCM) is a treasure of the Chinese nation, providing effective solutions to current medical requisites. Various spectral techniques are undergoing continuous development and provide new and reliable means for evaluating the efficacy and quality of TCM. Because spectral techniques are noninvasive, convenient, and sensitive, they have been widely applied to in vitro and in vivo TCM evaluation systems. In this paper, previous achievements and current progress in the research on spectral technologies (including fluorescence spectroscopy, photoacoustic imaging, infrared thermal imaging, laser-induced breakdown spectroscopy, hyperspectral imaging, and surface enhanced Raman spectroscopy) are discussed. The advantages and disadvantages of each technology are also presented. Moreover, the future applications of spectral imaging to identify the origins, components, and pesticide residues of TCM in vitro are elucidated. Subsequently, the evaluation of the efficacy of TCM in vivo is presented. Identifying future applications of spectral imaging is anticipated to promote medical research as well as scientific and technological explorations. (c) 2023 The Author(s). Published by Elsevier B.V. on behalf of Xi'an Jiaotong University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Cistanche tubulosa (CT), a well-known traditional Chinese medicine, has always been processed with rice wine for the treatment of kidney-yang deficiency syndrome (KYDS) since time immemorial. To explore the effect of processing on the efficacy and metabolites of CT in vivo, a comprehensive method using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was established for the analysis of the altered endogenous metabolites in response to the intervention of the raw and processed CT in KYDS model and the metabolites of the absorbed compounds in rats after gastric perfusion. It was shown that CT could improve KYDS, and the effect of the processed product was more significant. A total of 47 differential metabolites were identified in urine. Pathway analysis proved that purine metabolism; alanine, aspartate, and glutamate metabolism; and citrate cycle were the main pathways. Furthermore, 53 prototypes and 48 metabolites have been detected in rats. This was the first systematic research focus on the metabolites of raw and processed CT in vivo, which could provide a scientific basis for explaining the increasing efficiency of the processed CT. Moreover, it provides a valuable strategy for analyzing the chemical components and metabolites of other TCM prescriptions. © 2023 John Wiley & Sons Ltd.

Euodiae Fructus, referred to as "Wuzhuyu" in Chinese, has been used as local and traditional herbal medicines in many regions, especially in China, Japan and Korea, for the treatment of gastrointestinal disorders, headache, emesis, aphtha, dermatophytosis, dysentery, etc. Substantial investigations into their chemical and pharmacological properties have been performed. Recently, interest in this plant has been focused on the different structural types of alkaloids like evodiamine, rutaecarpine, dehydroevodiamine and 1-methyl-2-undecyl-4(1H)-quinolone, which exhibit a wide range of pharmacological activities in preclinical models, such as anticancer, antibacterial, anti-inflammatory, anti-cardiovascular disease, etc. This review summarizes the up-to-date and comprehensive information concerning the botany, traditional uses, phytochemistry, pharmacology of Euodiae Fructus together with the toxicology and quality control, and discusses the possible direction and scope for future research on this plant. © 2023. The Author(s).

Drug-metabolizing enzymes (DMEs), a diverse group of enzymes responsible for the metabolic elimination of drugs and other xenobiotics, have been recognized as the critical determinants to drug safety and efficacy. Deciphering and understanding the key roles of individual DMEs in drug metabolism and toxicity, as well as characterizing the interactions of central DMEs with xenobiotics require reliable, practical and highly specific tools for sensing the activities of these enzymes in biological systems. In the last few decades, the scientists have developed a variety of optical substrates for sensing human DMEs, parts of them have been successfully used for studying target enzyme(s) in tissue preparations and living systems. Herein, molecular design principals and recent advances in the development and applications of optical substrates for human DMEs have been reviewed systematically. Furthermore, the challenges and future perspectives in this field are also highlighted. The presented information offers a group of practical approaches and imaging tools for sensing DMEs activities in complex biological systems, which strongly facilitates high-throughput screening the modulators of target DMEs and studies on drug/herb-drug interactions, as well as promotes the fundamental researches for exploring the relevance of DMEs to human diseases and drug treatment outcomes. (C) 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.

Background: Donepezil is a first-line drug for the treatment of Alzheimer's disease (AD). However, there are no meta-analyses on efficacy and safety of high-dose versus standard-dose donepezil in the treatment of moderate-to-severe AD.Research Design and Methods: We searched for randomized controlled trials (RCTs) from 1993 to May 2021 PubMed, Cochrane Library, EMBASE, Web of Science, and Scopus databases. The outcomes of the meta-analysis included cognitive function, global assessment, and the incidence of adverse events and serious adverse events.Results: Five RCTs (2974 people) were included in this meta-analysis. The improvement of cognitive function was significant among the patients with the treatment of high-dose donepezil [SMD = 0.12, 95% CI: 0.03 similar to 0.22; p = 0.01]. Between the two groups, there was no significant difference in global assessment. Compared with standard-dose donepezil, there was no difference in the incidence of adverse events when high-dose donepezil was used. However, it was found that high-dose donepezil administration increased the risk of heart problems through subgroup analysis of the two serious adverse events.Conclusion: High-dose donepezil is more effective than standard-dose donepezil in improving cognitive function of the elderly with moderate-to-severe AD. However, more attention should be paid to patients with heart problems when high-dose donepezil was used.

PURPOSE: Large interindividual variability in the pharmacokinetic properties of docetaxel has been reported, with the clearance of docetaxel varying nearly six fold, in which pharmacogenetics of docetaxel may play an essential role in addition to physiological factors. The association between the gene polymorphism and risk of adverse clinical effects in docetaxel treated patients has been examined in several studies, but their conclusions are, to some extent, controversial. To clarify the role of gene polymorphism in the clinical outcomes of docetaxel treatment, a meta-analysis was performed in the present study.; METHODS: Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were employed to evaluate the impact of gene polymorphisms of CYP3A4, CYP3A5 and ABCB1. Four studies with 485 subjects were included in this study. Fixed or random-effects model was chosen according to heterogeneity to conduct the meta-analysis. Publication bias was evaluated by fail-safe numbers.; RESULTS: Significant association was identified between the ABCB1 C3435T (rs1045642) polymorphism and risk of short-term recurrent hematological toxicity (TT vs. CC+TC OR=2.91, 95% CI 1.30-6.52, P=0.009; TT vs. CC OR=4.23, 95% CI 1.69-10.57 P=0.002). The association of the ABCB1 G2677T/A (rs2032582) polymorphism with risk of fluid retention was statistically significant (T(A)/T(A) vs. GG+GT(A) OR=2.08, 95% CI 1.16-3.73, P=0.01). No statistically significant association between the CYP3A5 A6986G (rs776746) polymorphism and adverse effects was observed in this study. Due to the limitations of included literature, we did not conduct meta-analysis on CYP3A4 gene polymorphism and adverse effects.; CONCLUSION: An association between the ABCB1 C3435T (rs1045642), ABCB1 G2677T/A (rs2032582) polymorphism and risk of adverse effects of docetaxel was found by our meta-analysis. Namely, the TT homozygotes of the ABCB1 C3435T polymorphism may be associated with the risk of hematological toxicity. ABCB1 G2677T T(A)/T(A) genotype may be associated with the fluid retention.; TRAIL REGISTRATION: PROSPERO 2020 CRD42020203132. © 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Sophorae tonkinensis Radix et Rhizoma (S. tonkinensis) has been recorded as a 'poisonous' Chinese herbal medicine in Chinese Pharmacopoeia 2020. The clinical reaction reports of S. tonkinensis indicated its neurotoxicity; however, there still exists dispute about its toxic substances. At present, no report is available on the blood and brain prototype research of S. tonkinensis. Most studies focused on alkaloids and less on other compounds. Moreover, the constituents absorbed into the blood and brain have been rarely investigated so far. This study established a rapid and efficient qualitative analysis method using UPLC-Q-TOF-MSE to characterize the ingredients of S. tonkinensis and those entering into the rat's body after oral administration. A total of 91 compounds were identified in S. tonkinensis, of which 28 were confirmed by the standards. In addition, 30 and 19 prototypes were also first identified in the rat's blood and brain, respectively. It was found that most flavonoids, except alkaloids, were detected in the rat's body and distributed in the cerebrospinal fluid, suggesting that flavonoids may be one of the important toxic or effective substances of S. tonkinensis. This finding provides new clues and data for clarifying the toxicity or efficacy of this medicinal plant. © 2022 John Wiley & Sons, Ltd.