1.Olfactory Receptors Expressed in The Intestine and Their Functions
Pei-Wen YANG ; Meng-Meng YUAN ; Ying ZHOU ; Peng LI ; Gui-Hong QI ; Ying YANG ; Zhong-Yi MAO ; Meng-Sha ZHOU ; Xiao-Shuang MAO ; Jian-Ping XIE ; Yi-Nan YANG ; Shi-Hao SUN
Progress in Biochemistry and Biophysics 2026;53(3):534-549
Olfactory receptors (ORs) form the largest superfamily of G protein-coupled receptors (GPCRs). Traditionally recognized for their role in the nasal olfactory epithelium, where they mediate the sense of smell, accumulating evidence has firmly established their ectopic expression in non-olfactory tissues, including the intestine, lungs, and kidneys. The intestine, as the primary site for nutrient digestion and absorption, harbors a highly complex chemical environment. To adapt to this environment, the gut employs a sophisticated network of “chemosensors” to monitor luminal contents and maintain homeostasis. Among these sensors, intestinal ORs have emerged as crucial functional components, serving as a molecular bridge that connects environmental chemical signals—such as food-derived odorants—to specific physiological responses. This discovery has significantly deepened our understanding of how dietary flavors and compounds influence intestinal physiology at the molecular level. This review systematically summarizes the expression profiles, ligand classification, and biological functions of ORs within the gastrointestinal tract. Studies indicate that intestinal ORs exhibit distinct spatial distribution patterns across different gut segments and display cell-type specificity, particularly within enterocytes and enteroendocrine cells. These receptors function as versatile sensors capable of recognizing a wide variety of ligands, including exogenous dietary components, gut microbiota metabolites such as short-chain fatty acids, and endogenous small molecules like azelaic acid. Upon activation by specific ligands, intestinal ORs trigger intracellular signaling cascades, primarily involving the AC-cAMP-PKA pathway or calcium influx channels. A major focus of this review is to elucidate the molecular mechanisms by which these receptors regulate the secretion of gut hormones. Activation of specific ORs in enteroendocrine cells has been shown to stimulate the release of hormones such as glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and serotonin (5-HT), thereby modulating systemic energy metabolism, glucose homeostasis, and gastrointestinal motility. Furthermore, the review addresses the critical roles of ORs in immune regulation and pathology. Evidence suggests that specific ORs contribute to the maintenance of intestinal immune homeostasis and may offer protection against inflammation. Beyond their involvement in inflammatory responses, ORs such as Olfr78 have been shown to regulate the differentiation and function of intestinal endocrine cells. Similarly, Olfr544 has been demonstrated to alleviate intestinal inflammation by remodeling the gut microbiome and metabolome. These findings collectively suggest that specific ORs hold promise as therapeutic targets for mitigating intestinal inflammation and maintaining gut homeostasis. Additionally, the review explores the emerging role of ORs in cancer. Although OR expression is often downregulated in tumor tissues compared to normal mucosa, activation of specific ORs by certain ligands can inhibit tumor cell proliferation and migration and induce apoptosis via pathways such as MEK/ERK and p38 MAPK. Conversely, other receptors, such as OR7C1, may serve as biomarkers for cancer-initiating cells. In conclusion, intestinal ORs represent a vital component of the gut’s sensory network. The review also discusses the translational potential of these findings. By elucidating the precise pairing relationships between dietary components and specific ORs, novel therapeutic strategies could be developed. Intestinal ORs may thus emerge as promising targets for nutritional and pharmacological interventions in metabolic diseases, inflammatory bowel diseases, and malignancies.
2.The Dual Role of p21 in Hormone-related Cancers and Its Therapeutic Implications
Jia-Wen LI ; Yang CHEN ; Jia-Qi WANG ; Yu-Kai MA ; Zhi-Yi GUO
Progress in Biochemistry and Biophysics 2026;53(3):593-608
p21 (encoded by the CDKN1A gene) is a critical cell cycle regulatory protein endowed with versatile biological functions. In various sex hormone-related cancers, p21 exhibits a paradoxical dual role, capable of both inhibiting tumorigenesis and promoting cancer progression, exerting dual, often opposing, effects on cellular fate that are dictated by the specific context. The clinical targeting of p21 remains elusive, largely due to its functionally pleiotropic and context-dependent nature within intricate regulatory networks. During the initial, hormone-dependent phase of cancers like breast and prostate cancer, p21 expression and activity are largely governed by the transcriptional programs of estrogen or androgen receptor signaling. This hormonal regulation contributes to the control of tumor cell proliferation and underpins the initial efficacy of endocrine therapies. In contrast, as these diseases advance to late stages or evolve into non-hormone-dependent subtypes—exemplified by castration-resistant prostate cancer (CRPC) and specific forms of triple-negative breast cancer (TNBC)—these conventional hormonal control mechanisms often become dysfunctional or are entirely bypassed. This fundamental transition creates a critical therapeutic void, highlighting the urgent need to identify and exploit alternative molecular pathways to effectively target p21’s function. Promising strategies may include the precise modulation of its upstream transcriptional regulators, downstream effector proteins, or the intersecting parallel signaling networks that critically influence its activity. This review provides a systematic synthesis of the intricate and interconnected mechanisms that underpin the dual effects of p21 in sex hormone-related tumors. These mechanisms are categorized into three core, interrelated functional domains. (1) cell cycle regulation: p21 executes its canonical tumor-suppressive role by binding to and inhibiting cyclin-dependent kinases (CDKs) and by directly interacting with proliferating cell nuclear antigen (PCNA), thereby inducing cell cycle arrest, predominantly at the G1/S checkpoint; (2) apoptosis modulation: p21 exerts a highly context-dependent influence on programmed cell death, functioning either as a pro-apoptotic agent under severe genotoxic stress or as a pro-survival factor by inhibiting apoptosis through interactions with proteins like Bcl-2; (3) hormonal and signaling crosstalk: p21 is an integral node within broader cellular networks, engaging in direct physical interactions with hormone receptors(e.g., AR, ER) and participating in complex feedback loops with key oncogenic pathways, including PI3K/AKT, MAPK/ERK, and p53. Critically, the role of p21 is not static but highly dynamic. It can undergo a functional switch from tumor-suppressive to tumor-promoting in response to therapeutic pressures, metabolic alterations, or evolving tumor microenvironment cues. These adaptive shifts are frequently implicated in the development of therapy resistance and disease recurrence, particularly in advanced, hormone-resistant cancers. By synthesizing these insights, this review aims to establish a coherent theoretical framework to guide the future development of novel therapeutic strategies that target the p21 pathway. It underscores the necessity of moving beyond a simplistic, binary view of p21 and emphasizes the forthcoming challenges, such as the discovery of reliable biomarkers to predict its functional state and the rational design of context-specific pharmacological modulators to selectively harness its therapeutic potential.
3.Mechanisms of Jiangtang No. 3 Prescription in Alleviating Adipose Tissue Insulin Resistance in Diabetic Rats via TLR4/NF-κB/NLRP3 Signaling Pathway-mediated Inflammation
Tongxun WANG ; Lantian LIU ; Runqi LI ; Haoxiang LI ; Yi ZHAO ; Tian TIAN ; Rufeng MA ; Sihua GAO ; Dandan ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(4):109-117
ObjectiveTo observe the effects of Jiangtang No. 3 prescription on inflammatory pathways and insulin resistance-related indicators in rats with type 2 diabetes mellitus (T2DM), and to elucidate its molecular mechanism in combating diabetes. MethodsA T2DM rat model was established using a high-fat diet combined with intraperitoneal injection of streptozotocin (STZ). Successfully modeled rats were randomly assigned to the model group, metformin group, and low-, medium-, and high-dose Jiangtang No. 3 prescription groups, and a normal group was also set. Daily gavage was administered for 8 weeks as follows: metformin at 0.1 g·kg-1·d-1, Jiangtang No. 3 prescription granules at 1.62, 3.24, 6.48 g·kg-1·d-1 for the respective dose groups, and sterile water for the normal and model groups. Rat body weight, fasting blood glucose (FBG), oral glucose tolerance test (OGTT), and insulin tolerance test (ITT) were measured. After drug intervention, enzyme-linked immunosorbent assay (ELISA) was used to determine serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), non-esterified fatty acids (NEFA), interleukin (IL)-1β, IL-18, and insulin (INS). Hematoxylin-eosin (HE) staining was used to observe morphological changes in adipose tissue. Real-time quantitative PCR was used to detect the mRNA expression of Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB), NOD-like receptor protein 3 (NLRP3), Caspase-1, IL-1β, IL-18, and gasdermin D (GSDMD) in adipose tissue. Western blot was used to measure the corresponding protein expression levels. ResultsCompared with the model group, Jiangtang No. 3 prescription groups exhibited significantly increased body weight (P<0.05, P<0.01), significantly reduced FBG (P<0.05, P<0.01), significant reductions in TC, TG, NEFA, and LDL (P<0.05, P<0.01), and a significant increase in HDL (P<0.01). Serum levels of inflammatory mediators IL-1β and IL-18 were significantly decreased (P<0.01), the homeostatic model assessment of insulin resistance (HOMA-IR) index was significantly reduced (P<0.05, P<0.01), and adipose tissue pathology was improved. The protein expression levels of TLR4, NF-κB, NLRP3, Caspase-1, IL-1β, IL-18, and GSDMD were markedly decreased (P<0.05, P<0.01), and the mRNA expression levels of these indicators were also significantly downregulated (P<0.05, P<0.01). Some effects were superior to those of the positive control drug metformin, and certain indicators exhibited dose-dependent improvements. ConclusionT2DM rats display significant inflammatory responses, disordered glucose and lipid metabolism, and insulin resistance. Jiangtang No. 3 prescription effectively suppresses inflammatory mediators, improves glucose and lipid metabolism and insulin resistance, and ameliorates pathological changes in adipose tissue. Its mechanism may be related to the regulation of the TLR4/NF-κB/NLRP3 signaling pathway in visceral adipose tissue, thereby influencing downstream inflammatory mediators.
4.Effects of a school based integrated horticulture curriculum intervention on 24 hour activity behaviors in third grade primary school students
YU Ruida, ZHANG Hao, RONG Siyu, YI Qing, QI Yufei
Chinese Journal of School Health 2026;47(2):199-202
Objective:
To explore the effects of the school based integrated horticulture curriculum intervention on 24 hour activity behaviors among third grade primary school students, so as to provide reference for promoting children s health.
Methods:
In September 2023, a convenience sampling method was used to select 90 third grade primary school students from a primary school in Changsha. Participants were randomly assigned to an intervention group ( n =45) and a control group ( n =45) using a random number table. From February to May 2024, the intervention group received a 12 week integrated curriculum intervention, consisting of two 60 minute sessions per week and covering horticultural practice, home-school collaborative tasks and nutrition knowledge education. The control group continued with routine labor education courses. The triaxial accelerometer and multi sensor sleep monitoring device were used to objectively measure light intensity physical activity (LPA), moderate to vigorous physical activity (MVPA), screen based sedentary behavior (SSB) and sleep (SLP), durations in both groups. Data were analyzed using generalized estimating equations (GEE) and Mann-Whitney U tests.
Results:
The time, group and interaction effects of MVPA time and SLP time before and after intervention in two groups of primary school students were not statistically significant (Wald χ 2=1.54, 2.97, 0.85 ; 0.75, 1.05, 0.48), and the group effect of LPA time (Wald χ 2=1.24) and the time and group effects (Wald χ 2=3.02, 1.18 ) were not statistically significant (all P >0.05). There were statistically significant time and interaction effects for LPA time, as well as interaction effect for SSB time in two groups of primary school students before and after intervention (Wald χ 2=4.78, 3.95, 12.60, all P <0.05). After intervention, LPA time of intervention group [152.23(59.15, 245.80)min] was higher than that of control group [120.70(29.90, 201.20)min], and SSB time of intervention group [55.50(30.00, 125.50)min] was lower than that of control group [220.00(60.00, 285.00)min], with statistically significant differences ( Z =-2.46, -4.48, both P <0.05).
Conclusion
The school horticulture curriculum effectively enhances daily LPA and reduces SSB among third grade primary school students.
5.Construction of quality control evaluation indicators for common diseases surveillance among students
CUI Mengjie, MENG La, MA Qi, XING Yi
Chinese Journal of School Health 2025;46(6):894-898
Objective:
To construct a quality control evaluation indicator system for the surveillance of common diseases among students, so as to provide a reference for the quality control of surveillance projects.
Methods:
Based on literature review and expert interviews, a preliminary framework and candidate indicators were developed from June to August in 2024. Twenty domain experts participated in two rounds of Delphi consultations conducted via email, providing importance ratings, judgment basis, familiarity levels, and feasibility assessments for each indicator. And a quality control evaluation indicator system for the surveillance of common diseases among students was ultimately constructed.
Results:
The consulted experts aged 33-53, with an average age of (45.25±5.03) years, were from government health administration departments( n =1), centers for disease control and prevention at different levels( n =16), academic and research institutions( n =3). Their work experience in school health related fields ranged from 6 to 33 years, with an average of (16.70±8.25) years. The activeness of experts in both rounds of consultation was 100%, the mean expert authority coefficient was 0.90, and the mean feasibility evaluation was 0.75. Kendall s W test showed that the expert coordination coefficient for the first round was 0.26, and for the second round, it was 0.33 ( P <0.01). After two rounds of expert consultation, a set of quality control evaluation indicators for the surveillance of common diseases among students was ultimately constructed, including 6 first level indicators, 19 second level indicators, and 37 third level indicators.
Conclusion
The scientifically developed evaluation indicator system facilitates high quality implementation of student common disease surveillance programs.
6.Clinical features of anti-leucine rich glioma inactivated 1 antibody autoimmune encephalitis
Yongfang LI ; Yi TANG ; Qi QIN
Journal of Apoplexy and Nervous Diseases 2025;42(6):512-516
Objective To investigate the clinical manifestations and prognosis of patients with anti-leucine rich glioma inactivated 1(LGI1)antibody encephalitis. Methods A retrospective analysis was performed for the data of patients with anti-LGI1 antibody encephalitis who were hospitalized in Department of Neurology,Xuanwu Hospital,Capital Medical University,from September 2019 to December 2023,including clinical features,treatment,and prognosis. Results A total of 80 patients were enrolled,including 48 male patients and 32 female patients. Of all 80 patients,51(63.8%)had the initial symptom of epilepsy,13(16.3%)had the initial symptom of faciobrachial dystonic seizures,26(32.5%)had the initial symptom of cognitive impairment,and 12(15%)had the initial symptom of mental and behavioral disorders. As for comorbidities,there were 28 patients(35%)with hyponatremia,22(27.5%)with Hashimoto's thyroiditis,and 5(6.25%)with tumor. All 80 patients tested positive for serum LGI1 antibody,and 69(86.3%)tested positive for LGI1 antibody in cerebrospinal fluid. Among the 80 patients,37(46.25%)had abnormalities on magnetic resonance imaging,and 30 had abnormalities on 18F-FDG PET/CT. There were 50 patients with abnormalities on video electroencephalography. A total of 77 patients received first-line immunotherapy,and after follow-up for 1 year,19.4% of the patients had the sequela of seizure,59.7% of the patients had deterioration of the memory,and 48.6% of the patients had mental and behavioral disorders. Conclusion Epilepsy,cognitive impairment,and mental and behavior disorders are the most common manifestations of anti-LGI1 antibody encephalitis. There is generally a good prognosis after immunotherapy,with the sequelae of cognitive impairment and mental and behavioral disorders.
7.Effects of Non-invasive Light Flicker on Functional Properties of Primary Visual Cortex in Adult Mice
Xue-Qi LI ; Yi-Feng ZHOU ; Guang-Wei XU
Progress in Biochemistry and Biophysics 2025;52(9):2360-2375
ObjectiveAs the central hub of the classical visual pathway, the primary visual cortex not only encodes and processes visual information but also establishes dense neural circuit connections with higher-order cognitive brain regions. Numerous studies have shown that 40 Hz flicker stimulation can induce γ oscillations in the brain and significantly improve learning and cognitive impairments in patients with neurodegenerative diseases. Moreover, flickering light phenomena naturally occur in daily environments. Given that the primary visual cortex serves as the brain’s first cortical hub for receiving visual input, it is essential to comprehensively understand how non-invasive light flicker stimulation modulates its information processing mechanisms. This study systematically investigates the effects of non-invasive light flicker stimulation at different frequencies on the functional properties of neurons in the primary visual cortex of adult mice, aiming to uncover how such stimulation modulates this region and, consequently, affects overall brain function. MethodsThree groups of adult mice (approximately 12 weeks old) were exposed to light flicker stimulation at frequencies of 20 Hz, 40 Hz, and 60 Hz, respectively, for a duration of two months. A control group was exposed to the same light intensity without flickering. Following the stimulation period, in vivo multi-channel electrophysiological recordings were conducted. During these recordings, anesthetized mice were presented with various types of moving sinusoidal light gratings to assess the effects of different flicker frequencies on the functional properties of neurons in the primary visual cortex. ResultsThe experimental results demonstrate that two months of light flicker stimulation at 20 Hz, 40 Hz, and 60 Hz enhances the orientation tuning capabilities of neurons in the primary visual cortex. Specifically, 40 Hz and 60 Hz stimulation improved contrast sensitivity, whereas 20 Hz had no significant effect. Further analysis revealed that all three frequencies reduced neuronal response variability (as measured by the Fano factor), increased the signal-to-noise ratio, and decreased noise correlation (rsc) between neurons. ConclusionNon-invasive light flicker stimulation enhances orientation tuning (e.g., orientation bias index) and contrast sensitivity (e.g., contrast threshold and C50) in neurons of the primary visual cortex. This enhancement is likely due to improved information processing efficiency, characterized by reduced neuronal variability and increased signal-to-noise ratio. These findings suggest that the primary visual cortex can achieve precise and efficient information encoding in complex lighting environments by selectively adapting to different flicker frequencies and optimizing receptive field properties. This study provides new experimental evidence on how various types of light flicker influence visual perception and offers insights into the mechanisms through which specific frequencies enhance brain function.
8.Effect of Stasis-dispelling and Detoxifying Therapy on Clinical Efficacy and JNK Signaling Pathway-related Protein Expression in Endometriosis Patients with Syndrome of Kidney Deficiency and Blood Stasis
Tingting WANG ; Zhaokang QI ; Jinxin REN ; Shuai ZHAO ; Chunxiao WEI ; Yi YU ; Fang LIAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):120-129
ObjectiveTo observe the clinical efficacy of the stasis-dispelling and detoxifying therapy in endometriosis (EMs) patients with the syndrome of kidney deficiency and blood stasis and the effects of this therapy on the expression levels of proteins related to the c-Jun N-terminal kinase (JNK) signaling pathway. MethodsA total of 72 patients with EMs due to kidney deficiency and blood stasis who met the criteria at the Integrated Traditional Chinese and Western Medicine Center for Reproduction and Genetics of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from March 2024 to February 2025 were selected and randomized into a treatment group and a control group, with 36 patients in each group. Another 36 patients undergoing in vitro fertilization-embryo transfer (IVF-ET) due to male factors alone were selected as the blank group. The treatment group took the Zishen Quyu Jiedu formula orally, while the control group and the blank group took placebos. The treatment course encompassed the cycle before ovarian stimulation and the oocyte retrieval cycle. The TCM syndrome score of kidney deficiency and blood stasis, as well as the serum level of cancer antigen 125 (CA125), were evaluated at the time of enrollment (before treatment) and on the trigger day (after treatment). Serum levels of sex hormones were measured on day 2 of the menstrual cycle. On the trigger day, the duration and dosage of gonadotropin (Gn) administration and the serum levels of hormones on the day of human chorionic gonadotropin (HCG) injection were assessed. Embryo outcomes were evaluated 3 days after oocyte retrieval, and clinical pregnancy rates were assessed 28 days after embryo transfer. The baseline data of three groups were observed. The TCM syndrome scores and serum CA125 levels before and after treatment were compared between the treatment and control groups. The baseline endocrine levels, Gn days, Gn dosage, hormone levels on the day of HCG administration, number of oocytes retrieved, number of 2 pronucleus (2PN) fertilizations, number of available embryos, high-quality embryo rate, and clinical pregnancy rate were also assessed in all three groups. Six patients from each group were selected for determination of the protein levels of JNK, c-Jun, and nuclear receptor subfamily 4 group A member 2 (NR4A2) in ovarian granulosa cells (GCs) on the day of oocyte retrieval by Western blot. Results(1) There were no statistically significant differences in the baseline data among three groups, indicating comparability. (2) Compared with the baseline within the same group, the treatment group showed a decrease in the syndrome score of kidney deficiency and blood stasis after treatment. After treatment, serum CA125 levels decreased in both groups (P<0.05), with a more substantial reduction in the treatment group, resulting in a difference between the two groups (P<0.05). (3) There were no significant differences among three groups in terms of baseline serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and progesterone (P), as well as the duration and dosage of Gn administration and the serum levels of LH, E2, and P on the day of HCG administration. (4) For embryo outcomes, the number of oocytes retrieved, 2PN fertilizations, available embryos, and high-quality embryo rates in the treatment group and the blank group were higher than those in the control group (P<0.05), and the treatment group and the blank group had similar 2PN fertilizations. (5) There were differences in clinical pregnancy rate among three groups (P<0.05), and the treatment group had higher pregnancy rate than the control and blank groups. (6) The protein levels of JNK, c-Jun, and NR4A2 in the GCs of the treatment group were lower than those in the control group (P<0.01) and close to those in the blank group (P<0.01). (7) No obvious adverse reactions were observed in any of the subjects during the clinical observation process. ConclusionZishen Quyu Jiedu formula can ameliorate the clinical symptoms of patients with EMs due to kidney deficiency and blood stasis, reduce the serum CA125 level, increase the number of oocytes retrieved, 2PN fertilizations, available embryos, and high-quality embryo rate, and improve pregnancy outcomes. The mechanism may involve downregulating the levels of JNK, c-Jun, and NR4A2 to reduce the apoptosis of ovarian GCs and improve the ovarian function in the patients.
9.Effect of Stasis-dispelling and Detoxifying Therapy on Clinical Efficacy and JNK Signaling Pathway-related Protein Expression in Endometriosis Patients with Syndrome of Kidney Deficiency and Blood Stasis
Tingting WANG ; Zhaokang QI ; Jinxin REN ; Shuai ZHAO ; Chunxiao WEI ; Yi YU ; Fang LIAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):120-129
ObjectiveTo observe the clinical efficacy of the stasis-dispelling and detoxifying therapy in endometriosis (EMs) patients with the syndrome of kidney deficiency and blood stasis and the effects of this therapy on the expression levels of proteins related to the c-Jun N-terminal kinase (JNK) signaling pathway. MethodsA total of 72 patients with EMs due to kidney deficiency and blood stasis who met the criteria at the Integrated Traditional Chinese and Western Medicine Center for Reproduction and Genetics of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from March 2024 to February 2025 were selected and randomized into a treatment group and a control group, with 36 patients in each group. Another 36 patients undergoing in vitro fertilization-embryo transfer (IVF-ET) due to male factors alone were selected as the blank group. The treatment group took the Zishen Quyu Jiedu formula orally, while the control group and the blank group took placebos. The treatment course encompassed the cycle before ovarian stimulation and the oocyte retrieval cycle. The TCM syndrome score of kidney deficiency and blood stasis, as well as the serum level of cancer antigen 125 (CA125), were evaluated at the time of enrollment (before treatment) and on the trigger day (after treatment). Serum levels of sex hormones were measured on day 2 of the menstrual cycle. On the trigger day, the duration and dosage of gonadotropin (Gn) administration and the serum levels of hormones on the day of human chorionic gonadotropin (HCG) injection were assessed. Embryo outcomes were evaluated 3 days after oocyte retrieval, and clinical pregnancy rates were assessed 28 days after embryo transfer. The baseline data of three groups were observed. The TCM syndrome scores and serum CA125 levels before and after treatment were compared between the treatment and control groups. The baseline endocrine levels, Gn days, Gn dosage, hormone levels on the day of HCG administration, number of oocytes retrieved, number of 2 pronucleus (2PN) fertilizations, number of available embryos, high-quality embryo rate, and clinical pregnancy rate were also assessed in all three groups. Six patients from each group were selected for determination of the protein levels of JNK, c-Jun, and nuclear receptor subfamily 4 group A member 2 (NR4A2) in ovarian granulosa cells (GCs) on the day of oocyte retrieval by Western blot. Results(1) There were no statistically significant differences in the baseline data among three groups, indicating comparability. (2) Compared with the baseline within the same group, the treatment group showed a decrease in the syndrome score of kidney deficiency and blood stasis after treatment. After treatment, serum CA125 levels decreased in both groups (P<0.05), with a more substantial reduction in the treatment group, resulting in a difference between the two groups (P<0.05). (3) There were no significant differences among three groups in terms of baseline serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and progesterone (P), as well as the duration and dosage of Gn administration and the serum levels of LH, E2, and P on the day of HCG administration. (4) For embryo outcomes, the number of oocytes retrieved, 2PN fertilizations, available embryos, and high-quality embryo rates in the treatment group and the blank group were higher than those in the control group (P<0.05), and the treatment group and the blank group had similar 2PN fertilizations. (5) There were differences in clinical pregnancy rate among three groups (P<0.05), and the treatment group had higher pregnancy rate than the control and blank groups. (6) The protein levels of JNK, c-Jun, and NR4A2 in the GCs of the treatment group were lower than those in the control group (P<0.01) and close to those in the blank group (P<0.01). (7) No obvious adverse reactions were observed in any of the subjects during the clinical observation process. ConclusionZishen Quyu Jiedu formula can ameliorate the clinical symptoms of patients with EMs due to kidney deficiency and blood stasis, reduce the serum CA125 level, increase the number of oocytes retrieved, 2PN fertilizations, available embryos, and high-quality embryo rate, and improve pregnancy outcomes. The mechanism may involve downregulating the levels of JNK, c-Jun, and NR4A2 to reduce the apoptosis of ovarian GCs and improve the ovarian function in the patients.
10.Ameliorative effect of patchouli alcohol on mice with lung-heat syndrome based on PI3K/Akt/NF-κB pathway
Linze LI ; Yi LI ; Haoyi QIAO ; Jiakang JIAO ; Qi ZHANG ; Xiaofang WU ; Xingyu ZHAO ; Yinming ZHAO ; Chun WANG ; Jianjun ZHANG ; Linyuan WANG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(4):459-470
Objective:
To investigate the therapeutic effect of patchouli alcohol on mice with lung-heat syndrome based on the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/nuclear factor-kappa B(NF-κB) signaling pathway.
Methods:
First, network pharmacology was used to predict the potential targets of patchouli alcohol in the treatment of lung-heat syndrome, and a "component-disease-key target" network was constructed for pathway analysis. Then, 40 BALB/c mice were assigned to the normal, lung-heat model, honeysuckle, and low-dose and high-dose patchouli alcohol groups. All groups, except the blank group, were intranasally infected with 50 μL (103 TCID50) of influenza virus solution. After two hours of infection, mice were treated once a day for seven consecutive days. The therapeutic mechanism of patchouli alcohol was explored by measuring pulmonary inflammatory factors, the PI3K/Akt/NF-κB pathway, hypothalamic fever markers (PGE2, cAMP, cGMP levels), rectal temperature, and tissue energy metabolism.
Results:
Network pharmacology identified 135 target genes related to patchouli alcohol and lung-heat syndrome, with the key targets being STAT3, H1F1A, and NF-κB1. In animal experiments, patchouli alcohol significantly alleviated influenza virus-induced lung inflammatory damage in mice with lung-heat syndrome, inhibited the expression of TNF-α and IL-6 in lung tissues(P<0.01), and suppressed the activation of the PI3K/Akt/NF-κB pathway. It also reduced hypothalamic levels of PGE2 and cAMP(P<0.01), suppressed the increase in rectal temperature, significantly decreased liver glycogen and pyruvate levels(P<0.01), and increased the activities of SDH, LDH, and Na+ -K+ -ATPase in the liver(P<0.01)
Conclusion
Patchouli alcohol improves the symptoms of lung-heat syndrome in mice by inhibiting the activation of the PI3K/Akt/NF-κB pathway, reducing proinflammatory cytokines and inflammatory damage, and regulating hypothalamic fever markers and energy metabolism.


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