1.Herbal Textual Research on Bambusae Succus in Famous Classical Formulas
Yu SHI ; Feng ZHOU ; Yihan WANG ; Yanmeng LIU ; Ming YANG ; Zhiping CHEN ; Jiangshan ZHANG ; Conglong XU ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):231-239
This article systematically reviews and examines the historical evolution of Bambusae Succus as a medicinal material, covering aspects such as nomenclature, origin, geographical distribution, harvesting and processing methods, quality assessment, therapeutic effects and indications, by consulting ancient herbal texts, medical compendia, and modern literature. The aim is to provide a reference for the development and utilization of famous classical formulas containing this herb. Research indicated that Bambusae Succus was first documented in the Shennong Bencaojing during the Han dynasty, with Zhuli being the standard name used throughout history, alongside aliases like Zhuzhi, Zhuyou and Huoquan. Historically, the primary source of Bambusae Succus has been Phyllostachys nigra var. henonis(Danzhu), although other species such as Pleioblastus amarus and Bambusa emeiensis have also been used medicinally. Ancient records predominantly noted its origin in Yizhou(present-day Chengdu and surrounding areas in Sichuan) and the Wuling region(between present-day Hunan, Guangdong, Guangxi and Jiangxi provinces), while contemporary sources are mainly from regions south of the Yangtze River and southwestern China. Traditionally, Bambusae Succus was harvested from bamboo that had grown for exactly one year, today, it can be collected year-round without strict age requirements. Ancient preparation methods included direct fire roasting or dry distillation, whereas modern industrial production employs dry distillation, reflux extraction, and percolation. In terms of quality evaluation, ancient texts considered a sweet taste to be superior, while today, clarity and transparency are prioritized. Historically, Bambusae Succus was characterized as sweet and cold nature, targeting the lung and stomach meridians, with uses evolving from clearing heat and resolving phlegm to nourishing Yin, moistening dryness, and relaxing tendons and unblocking meridians. Modern descriptions classify it as sweet, bitter, and cold in nature, affecting the heart, liver, and lung meridians, with functions including clearing heat, resolving phlegm, and facilitating orifices. It is indicated for conditions such as stroke with phlegm confusion, lung heat with phlegm congestion, convulsions, epilepsy, excessive phlegm in febrile diseases, high fever with thirst, irritability during pregnancy, and tetanus, with more clearly defined applications. Based on the results of the research, it is recommended that when developing and utilizing famous classical formulas containing Bambusae Succus, the one-year-old Phyllostachys nigra var. Henonis, which has been highly praised throughout history, should be selected as the source material. Industrial production should adopt the dry distillation method. Furthermore, in-depth research should be conducted on the modern technological characterization of the traditional quality control indicator of sweet taste, and reasonable modern quality control standards should be established.
2.Herbal Textual Research on Patriniae Herba in Famous Classical Formulas
Yu SHI ; Zhen ZENG ; Feng ZHOU ; Yihan WANG ; Yanmeng LIU ; Yang YANG ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):248-257
By consulting ancient and modern literature, this article systematically reviews and verifies the historical evolution of the herbal medicine known as Baijiang across various dimensions, including name, origin, scientific name verification, medicinal parts, production area, quality, harvesting and processing, as well as its nature, taste, and therapeutic effects, in order to provide a reference for the development and utilization of famous classical formulas containing Patriniae Herba. Patriniae Herba has a long history of use. It derives its name from the distinctive musty odor of its roots, which resembles spoiled soy sauce. However, due to its alias Kucai, there has been much confusion with other plants. Since the Ming dynasty, various plants have been used interchangeably as Baijiang. Herbal textual research showed that Patriniae Herba was first recorded in Shennong Bencaojing, and throughout history, Baijiang has been recognized as its standard name, though it has also been known by alternative names such as Luchang, Lujiang, and Suanyi. The main sources used throughout the ages were Patrinia scabiosaefolia or P. villosa, which is consistent with the 1977 edition of the Pharmacopoeia of the People's Republic of China. However, while the roots were traditionally used medicinally, the whole plant is now more commonly used in modern practice. In addition, the whole plants of Thlaspi arvense from the Cruciferae family and Sonchus brachyotus from the Compositae family are commonly used as regional substitutes for Baijiang. According to ancient records, Patriniae Herba was primarily found in Jiangxia(present-day eastern Hubei province) and Jiangdong(the region south of the lower reaches of the Yangtze River), but modern literature shows that it is distributed throughout the country without a distinct geographical origin. In ancient times, the roots were harvested in August and sun-dried, today, the whole plant is typically dug up in summer or autumn and sun-dried. In recent times, the quality has been summarized as being best when the roots are long, the leaves are abundant and green, and the aroma is strong. Regarding the processing, ancient methods often involved baking(drying over fire), while modern methods typically involve removing impurities, washing, and then cutting and drying the segments. The effects of Patriniae Herba are to clear heat and detoxify, eliminate blood stasis and drain pus. During the Han and Northern and Southern dynasties, it was used to treat skin diseases caused by heat, abscesses, postpartum diseases, and rheumatism, during the Five dynasties period, its therapeutic applications expanded to include diseases of the five senses, and by the modern era, conditions such as neurasthenia and insomnia were added. Regarding its properties and taste, it was recorded as bitter and neutral during the Han dynasty. By the Tang dynasty, it was slightly cold, with a taste of acrid and bitter. During the Yuan and Ming dynasties, it was mostly slightly cold and neutral, with a bitter and salty taste. In the Qing dynasty and modern times, it was mostly bitter and neutral, and in contemporary times, it has evolved to a taste of acrid, bitter, and cool. Based on the results of this study, it is recommended that when developing and utilizing famous classical formulas containing Patriniae Herba, one should select the entire herb of the historically mainstream sources, P. scabiosaefolia or P. villosa from the Valerianaceae family, and choose the processing method according to the prescription requirements. It is recommended to use raw products without specific requirements.
3.Herbal Textual Research on Patriniae Herba in Famous Classical Formulas
Yu SHI ; Zhen ZENG ; Feng ZHOU ; Yihan WANG ; Yanmeng LIU ; Yang YANG ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):248-257
By consulting ancient and modern literature, this article systematically reviews and verifies the historical evolution of the herbal medicine known as Baijiang across various dimensions, including name, origin, scientific name verification, medicinal parts, production area, quality, harvesting and processing, as well as its nature, taste, and therapeutic effects, in order to provide a reference for the development and utilization of famous classical formulas containing Patriniae Herba. Patriniae Herba has a long history of use. It derives its name from the distinctive musty odor of its roots, which resembles spoiled soy sauce. However, due to its alias Kucai, there has been much confusion with other plants. Since the Ming dynasty, various plants have been used interchangeably as Baijiang. Herbal textual research showed that Patriniae Herba was first recorded in Shennong Bencaojing, and throughout history, Baijiang has been recognized as its standard name, though it has also been known by alternative names such as Luchang, Lujiang, and Suanyi. The main sources used throughout the ages were Patrinia scabiosaefolia or P. villosa, which is consistent with the 1977 edition of the Pharmacopoeia of the People's Republic of China. However, while the roots were traditionally used medicinally, the whole plant is now more commonly used in modern practice. In addition, the whole plants of Thlaspi arvense from the Cruciferae family and Sonchus brachyotus from the Compositae family are commonly used as regional substitutes for Baijiang. According to ancient records, Patriniae Herba was primarily found in Jiangxia(present-day eastern Hubei province) and Jiangdong(the region south of the lower reaches of the Yangtze River), but modern literature shows that it is distributed throughout the country without a distinct geographical origin. In ancient times, the roots were harvested in August and sun-dried, today, the whole plant is typically dug up in summer or autumn and sun-dried. In recent times, the quality has been summarized as being best when the roots are long, the leaves are abundant and green, and the aroma is strong. Regarding the processing, ancient methods often involved baking(drying over fire), while modern methods typically involve removing impurities, washing, and then cutting and drying the segments. The effects of Patriniae Herba are to clear heat and detoxify, eliminate blood stasis and drain pus. During the Han and Northern and Southern dynasties, it was used to treat skin diseases caused by heat, abscesses, postpartum diseases, and rheumatism, during the Five dynasties period, its therapeutic applications expanded to include diseases of the five senses, and by the modern era, conditions such as neurasthenia and insomnia were added. Regarding its properties and taste, it was recorded as bitter and neutral during the Han dynasty. By the Tang dynasty, it was slightly cold, with a taste of acrid and bitter. During the Yuan and Ming dynasties, it was mostly slightly cold and neutral, with a bitter and salty taste. In the Qing dynasty and modern times, it was mostly bitter and neutral, and in contemporary times, it has evolved to a taste of acrid, bitter, and cool. Based on the results of this study, it is recommended that when developing and utilizing famous classical formulas containing Patriniae Herba, one should select the entire herb of the historically mainstream sources, P. scabiosaefolia or P. villosa from the Valerianaceae family, and choose the processing method according to the prescription requirements. It is recommended to use raw products without specific requirements.
4.Comparison of Wild and Cultivated Bupleurum scorzonerifolium Based on Traditional Quality Evaluation
Changsheng YUAN ; Feng ZHOU ; Xingyu LIU ; Yu SHI ; Yihan WANG ; Huaizhu LI ; Yongliang LI ; Shan GUAN ; Huaizhong GAO ; Yanmeng LIU ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):203-214
ObjectiveTo characterize the quality differences among different germplasm and introduced varieties of Bupleurum scorzonerifolium roots(BSR), and explore the underlying molecular mechanisms, providing a basis for high-quality production and quality control. MethodsWild BSR from Yulin(YLW) served as the quality reference, we conducted comparative analysis among YLW, locally domesticated wild germplasm in Yulin(YLC3), Daqing germplasm introduced and cultivated in Yulin(YLDQC3), and locally cultivated germplasm in Daqing(DQC3). A combination of traditional pharmacognostic methods and modern multi-omics analyses was employed, including macroscopic traits(appearance, odor), microscopic features(proportions of cork, phloem, xylem), cell wall component contents(hemicellulose, cellulose, lignin), carbohydrate contents(starch, water-soluble polysaccharides), marker compound contents(ethanol-soluble extracts, total saponins, liposoluble extracts, and saikosaponins A, B2, C, D), metabolomics, and transcriptomics, in order to systematically characterize quality differences and investigate molecular mechanisms among these samples. ResultsMacroscopically, Yulin-produced BSR(YLW, YLC3, YLDQC3) exhibited significantly greater weight, length, and upper and middle diameters than Daqing-produced BSR(DQC3). Odor-wise, YLW and YLC3 had a a fragrance taste, YLDQC3 had a rancid oil odor, and DQC3 had a sweet and fragrant taste. Microscopically, Yulin germplasm(YLW, YLC3) and Daqing germplasm(YLDQC3, DQC3) shared similar structural features, respectively. However, Yulin germplasm showed significantly higher proportions of cork and phloem, as well as stronger xylem vessel staining intensity compared to Daqing germplasm. Regarding various component contents, Yulin germplasm contained significantly higher levels of ethanol-soluble extracts, total saponins, and saikosaponins A, B2, C, D, while Daqing germplasm had significantly higher levels of hemicellulose, starch, and liposoluble extracts. After introduction to Yulin, the Daqing germplasm(YLDQC3) showed increased starch, water-soluble polysaccharides and liposoluble extracts contents, decreased cell wall component content, but no significant difference in other component contents. Metabolomics revealed that saponins and terpenes accumulated significantly in Yulin germplasm, while alcohols and aldehydes accumulated predominantly in Daqing germplasm. Transcriptomics indicated similar gene expression patterns within the same germplasm but specificity between different germplasms. Integrative metabolomic-transcriptomic analysis identified 145 potential key genes associated with the saikosaponin biosynthesis pathway, including one acetyl-coenzyme A(CoA) acetyltransferase gene(ACAT), one 3-hydroxy-3-methylglutaryl-coenzyme A synthase gene(HMGS), two hydroxymethylglutaryl-CoA(HMG-CoA) reductase genes(HMG), one phosphomevalonate kinase gene(PMK), one 1-deoxy-D-xylose-5-phosphate synthase gene(CLA), one hydroxymethylbuten-1-aldol synthase gene(HDR), two farnesyl pyrophosphate synthase genes(FPPS), one squalene synthase gene(SQS), one β-amyrin synthase gene(BAS), 102 cytochrome P450(CYP450) gene family members, and 32 uridine diphosphate-glucuronosyltransferase(UGT) gene family members. ConclusionAmong the three cultivated types, YLC3 most closely resembles YLW in appearance, microscopic features, contents of major bioactive constituents, metabolomic and transcriptomic profiles. Yulin germplasm exhibits superior saponin synthesis capability compared to Daqing germplasm, and Yulin region is more suitable for the growth of B. scorzonerifolium. Based on these findings, it is recommended that artificial cultivation in northern Shaanxi and similar regions utilize the local Yulin germplasm source cultivated for at least three years.
5.Traditional Chinese Medicine Regulates Related Signaling Pathways to Prevent and Control Breast Cancer and Precancerous Lesions: A Review
Yifei ZENG ; Di ZHAO ; Junyue WANG ; Mengjie WANG ; Yubo GUO ; Yu ZHOU ; Dongxiao ZHANG ; Wenjie ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):290-301
Breast cancer has become the malignant tumor with the highest incidence rate among women, seriously threatening the life and health of women all over the world. The pathogenic factors and development mechanisms of breast cancer are complex and diverse. The development of breast cells from ordinary hyperplasia to atypical hyperplasia, and from pre-cancerous lesions to cancerous lesions, is a long-term progressive process. Therefore, early screening and prevention of breast cancer is particularly important. Western medicine has a relatively mature treatment program for breast cancer, which is mainly based on surgery and systemic treatment, whereas the ensuing complications and adverse reactions often bring a heavy burden to patients. For the precancerous lesions of breast cancer, surgery is also the mainstay of treatment. In recent years, traditional Chinese medicine (TCM) has increasingly highlighted its advantages in the prevention and treatment of breast cancer. Increasing studies have shown that in the prevention and treatment of breast cancer and pre-cancerous lesions, TCM compound prescriptions, single herbs or herb pairs, and active components are able to regulate a variety of intracellular signaling pathways through multi-targets to inhibit the proliferation and invasion, promote the apoptosis and autophagy of tumor cells, and regulate the cell cycle and the immune microenvironment, thus exerting anti-tumor effects. At the same time, they can significantly attenuate the toxic side effects of radiotherapy and drug resistance of patients. However, the specific mechanisms of TCM in the prevention and treatment of breast cancer and precancerous lesions have not been fully clarified. The available studies are tanglesome regarding the TCM inhibition of tumor development through the regulation of classical signaling pathways such as phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), Wnt/β-catenin, and Notch, which still need to be verified by a large number of clinical and experimental studies. Therefore, this paper reviews the research progress in the prevention and treatment of breast cancer and precancerous lesions by TCM through interfering with the relevant signaling pathways in recent years, aiming to summarize the possible mechanisms of TCM in the prevention and treatment of breast cancer and provide references for subsequent studies.
6.Lysosomes as Regulators of Cancer Stemness and Drug Resistance
Fa-Xiao ZHOU ; Di-Ping YU ; Si-Qi TAN ; Hong-Yu DUAN ; Xiao-Ming WU
Progress in Biochemistry and Biophysics 2026;53(4):951-967
Cancer stem cells (CSCs) represent a distinct subpopulation of cells characterized by self-renewal capacity, differentiation potential, and critical roles in driving tumor progression, therapeutic resistance, recurrence, and maintenance of the tumor microenvironment. Targeting CSCs has emerged as a pivotal direction in cancer research, offering novel strategies to overcome drug resistance and prevent metastasis and relapse. Lysosomes, traditionally recognized as central organelles for intracellular degradation and recycling, are indispensable for cellular homeostasis. Dysregulation of lysosomal function is intimately linked to various diseases, including cancer. In tumors, aberrant lysosomal activity can promote malignant progression through mechanisms such as altering metabolic pathways, enhancing lysosomal exocytosis, modulating drug resistance, and interfering with autophagy-lysosomal pathways. Recent studies have underscored the involvement of lysosomes in regulating CSC properties. This review synthesizes findings on lysosomal regulation of CSCs through the following aspects. (1) Lysosomes exert complex and critical bidirectional control over CSC stemness maintenance through three degradation pathways that are dependent on their degradative function. (i) The lysophagy pathway. This pathway exhibits dual roles. Activation can sustain CSC functions; for instance, in glioblastoma, hypoxia upregulates Gal-8 via the STAT3/HIF1α signaling axis to induce autophagy, supporting stem cell survival. In head and neck squamous cell carcinoma, degradation of GSK3β activates the Wnt pathway, enhancing stemness. Conversely, this pathway can suppress stemness by degrading stemness-related proteins such as BMI-1 and OCT4A, thereby impairing CSC self-renewal capacity. (ii) Mitophagy pathway. In non-small cell lung cancer stem cells, mitophagy-related mechanisms, such as the accumulation of mitochondrial DNA (mtDNA) activating the TLR9-Notch1-AMPK signaling axis, have been shown to promote CSC proliferation. (iii) Autophagosome-dependent lysosomal degradation pathway. This pathway directly regulates stemness-related proteins in a bidirectional manner. Enhanced degradative function can promote CSC properties, exemplified by the degradation of NUMB to activate Notch signaling. Conversely, attenuated degradative function can also enhance stemness by stabilizing oncoproteins (e.g., protecting Frizzled-1 from degradation to sustain Wnt signaling) or preventing the degradation of tumor suppressors (e.g., inhibiting Notch degradation). (2) Constituent proteins of lysosomes, including membrane proteins and luminal acid hydrolases, participate in regulating CSC stemness. Regarding membrane proteins, LAMP2A facilitates chaperone-mediated autophagy to maintain stemness in glioblastoma and ovarian cancer. V-ATPase, by maintaining an acidic luminal environment, promotes proliferation and drug resistance in glioma stem cells. Among hydrolases, cathepsins B and L are highly expressed in pancreatic and ovarian cancers and correlate with poor prognosis. Furthermore, targeting lysosomes to induce lysosomal membrane permeabilization (LMP) triggers lysosome-mediated cell death, presenting a potential therapeutic strategy for eradicating CSCs.(3) The acidic luminal environment, single-membrane structure, and the presence of transmembrane transporters (e.g., ABCA3) enable lysosomes to passively trap or actively uptake and sequester chemotherapeutic drugs. Subsequent drug extrusion via exocytosis confers drug resistance. In CSCs, this lysosome-mediated drug sequestration, often cooperating with autophagy, establishes multimodal drug resistance. Therefore, targeting lysosomal function represents a potential strategy to overcome therapy resistance. The central role of lysosomes in regulating CSC stemness and resistance positions them as highly promising therapeutic targets. Strategies aimed at disrupting lysosomal function to selectively eliminate CSCs include: inhibiting the lysosome-autophagy system using agents like IITZ or lovastatin; inducing lysosomal membrane permeabilization (LMP) with compounds such as hexamethylene amiloride to compromise membrane stability; and disrupting the acidic luminal environment using drugs like siramesine or the K/H transport compound 2. In conclusion, lysosomes critically regulate CSC stemness maintenance and drug resistance through degradative pathways, membrane protein functions, luminal hydrolase activities, and drug sequestration mechanisms. This redefines the lysosome from a traditional “waste disposal unit” to a “signal integration center” in CSCs. The duality and context-dependency of lysosomal function in CSCs offer novel insights into the heterogeneity observed across different tumors. Targeting lysosomal vulnerabilities—such as inducing LMP, disrupting acidity, or blocking autophagic flux—provides a strategy to bypass canonical CSC resistance mechanisms and directly trigger cell death. This establishes the lysosome as a key target to overcome CSC-mediated therapy resistance, paving the way for developing diverse candidate drugs and innovative combination therapies in oncology.
7.The bridging role of programmed cell death in association between periodontitis and rheumatoid arthritis
GE Ruiyang ; ZHOU Yingying ; MAO Haowei ; HAN Lei ; CUI Di ; YAN Fuhua
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(6):457-465
Periodontitis and rheumatoid arthritis (RA) are chronic inflammatory diseases that share similar inflammatory mechanisms and characteristics. Programmed cell death (PCD) has recently garnered attention for its crucial role in regulating inflammation and maintaining tissue homeostasis, as well as for its potential to link these two diseases. The various forms of PCD--including apoptosis, pyroptosis, and necroptosis--are closely controlled by signaling pathways such as Toll-like receptor 4 (TLR4) /NF-κB and MAPK. These pathways determine cell fate and influence inflammatory responses, tissue destruction, and repair, and they both play important roles in the pathogenesis of RA and periodontitis. In periodontitis, periodontal pathogens such as Porphyromonas gingivalis (P. gingivalis) and its virulence factors, including lipopolysaccharide (LPS), induce pyroptosis and necroptosis in immune cells such as macrophages via the TLR4/NF-κB pathway, which leads to an excessive release of pro-inflammatory cytokines such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α. Concurrently, these pathogens inhibit the normal apoptotic process of immune cells, such as neutrophils, prolonging their survival, exacerbating immune imbalance, and aggravating periodontal tissue destruction. Similarly, in RA synovial tissue, fibroblast-like synoviocytes (FLS) acquire apoptosis resistance through signaling pathways such as the Bcl-2 family, JAK/STAT, and NF-κB, allowing for the consistent proliferation and secretion of matrix metalloproteinases and pro-inflammatory cytokines. Meanwhile, the continuous activation of pyroptotic pathways in neutrophils and macrophages results in the sustained release of IL-1β, further exacerbating synovial inflammation and bone destruction. Notably, dysregulated PCD fosters inter-organ crosstalk through shared inflammatory mediators and metabolic networks. Damage-associated molecular patterns (DAMPs) and cytokines that originate from periodontal lesions can spread systemically, influencing cell death processes in synovial and immune cells, thereby aggravating joint inflammation and bone erosion. By contrast, systemic inflammation in RA can upregulate osteoclastic activity or interfere with the normal apoptosis of periodontal cells via TNF-α and IL-6, ultimately intensifying periodontal immune imbalance. This review highlights the pivotal bridging role of PCD in the pathogenesis of both periodontitis and RA, providing a reference for therapeutic strategies that target cell death pathways to manage and potentially mitigate these diseases.
8.Current situation of medicinal animal breeding and research progress in sustainable utilization of resources.
Cheng-Cai ZHANG ; Jia WANG ; Yu-Jie ZHOU ; Xiao-Yu DAI ; Xiu-Fu WAN ; Chuan-Zhi KANG ; De-Hua WU ; Jia-Hui SUN ; Sheng WANG ; Lan-Ping GUO
China Journal of Chinese Materia Medica 2025;50(16):4397-4406
Traditional Chinese medicine(TCM) is the pillar for the development of motherland medicine, and animal medicine has a long history of application in China, characterized by wide resources, strong activity, definite efficacy, and great benefits. It has significant potential and important status in the consumption market of raw materials of TCM. In the context of global climate change, farming system alterations, and low renewability, the depletion of wild medicinal animal resources has accelerated. Accordingly, the conservation and sustainable utilization of wild resources of animal medicinal materials has become a problem that garners increasing attention and urgently needs to be solved. This paper summarizes the current situation of domestic and foreign medicinal animal breeding and research progress in industrial application in recent years and points out the issues related to standardized breeding, germplasm selection and breeding, and quality evaluation standards for medicinal animals. Furthermore, this paper discusses standardized breeding, quality standards, resource protection and utilization, and the search for alternative resources for rare and endangered medicinal animals. It proposes that researchers should systematically carry out in-depth basic research on animal medicine, improve the breeding scale and level of medicinal animals, employ modern technology to enhance the quality standards of medicinal materials, and strengthen the research and development of alternative resources. This approach aims to effectively address the relationship between protection and utilization and make a significant contribution to the sustainable development of medicinal animal resources and the animal-based Chinese medicinal material industry.
Animals
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Breeding
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China
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Medicine, Chinese Traditional
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Conservation of Natural Resources
9.Engineering cellular dephosphorylation boosts (+)-borneol production in yeast.
Haiyan ZHANG ; Peng CAI ; Juan GUO ; Jiaoqi GAO ; Linfeng XIE ; Ping SU ; Xiaoxin ZHAI ; Baolong JIN ; Guanghong CUI ; Yongjin J ZHOU ; Luqi HUANG
Acta Pharmaceutica Sinica B 2025;15(2):1171-1182
(+)-Borneol, the main component of "Natural Borneol" in the Chinese Pharmacopoeia, is a high-end spice and precious medicine. Plant extraction cannot meet the increasing demand for (+)-borneol, while microbial biosynthesis offers a sustainable supply route. However, its production was extremely low compared with other monoterpenes, even with extensively optimizing the mevalonate pathway. We found that the key challenge is the complex and unusual dephosphorylation reaction of bornyl diphosphate (BPP), which suffers the side-reaction and the competition from the cellular dephosphorylation process, especially lipid metabolism, thus limiting (+)-borneol synthesis. Here, we systematically optimized the dephosphorylation process by identifying, characterizing phosphatases, and balancing cellular dephosphorylation metabolism. For the first time, we identified two endogenous phosphatases and seven heterologous phosphatases, which significantly increased (+)-borneol production by up to 152%. By engineering BPP dephosphorylation and optimizing the MVA pathway, the production of (+)-borneol was increased by 33.8-fold, which enabled the production of 753 mg/L under fed-batch fermentation in shake flasks, so far the highest reported in the literature. This study showed that rewiring dephosphorylation metabolism was essential for high-level production of (+)-borneol in Saccharomyces cerevisiae, and balancing cellular dephosphorylation is also helpful for efficient biosynthesis of other terpenoids since all whose biosynthesis involves the dephosphorylation procedure.
10.Trends in intestinal aging: From underlying mechanisms to therapeutic strategies.
Yajun WANG ; Xueni ZHANG ; Mengli QING ; Wen DANG ; Xuemei BAI ; Yingjie WANG ; Di ZHOU ; Lingjuan ZHU ; Degang QING ; Juan ZHANG ; Gang CHEN ; Ning LI
Acta Pharmaceutica Sinica B 2025;15(7):3372-3403
Intestinal aging is central to systemic aging, characterized by a progressive decline in intestinal structure and function. The core mechanisms involve dysregulation of epithelial cell renewal and gut microbiota dysbiosis. In addition to previous results in model organisms like Drosophila melanogaster, recent studies have shown that in mammalian models, aging causes increased intestinal permeability and intestinal-derived systemic inflammation, thereby affecting longevity. Therefore, anti-intestinal aging can be an important strategy for reducing frailty and promoting longevity. There are three key gaps remaining in the study of intestinal aging: (1) overemphasis on aging-related diseases rather than the primary aging mechanisms; (2) lack of specific drugs or treatments to prevent or treat intestinal aging; (3) limited aging-specific dysbiosis research. In this review, the basic structures and renewal mechanisms of intestinal epithelium, and mechanisms and potential therapies for intestinal aging are discussed to advance understanding of the causes, consequences, and treatments of age-related intestinal dysfunction.


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