OBJECTIVE To investigate the mechanism of pachymic acid on renal injury in pregnancy induced hypertension （PIH） rats by regulating the silent information regulator transcript 1/peroxisome proliferator-activated receptor γ coactivator-1α （Sirt1/PGC-1α） pathway. METHODS Pregnant SD rats were prepared by co-caging and PIH model was induced using N-nitro-L- arginine methyl ester （L-NAME） method. PIH rats were randomly divided into model group， L-pachymic acid （low-dose pachymic acid， 10 mg/kg） group， H-pachymic acid （high-dose pachymic acid， 20 mg/kg） group， and H-pachymic acid+EX527 （20 mg/kg pachymic acid+10 mg/kg EX527） group， with 6 rats in each group. Another 6 normal pregnant rats were selected as blank group. Each group was given relevant medicine or solvent intragastrically or intraperitoneally daily， once a day， for 28 consecutive days. After the last administration， 24 h urinary protein and tail artery systolic blood pressure （SBP） were measured in pregnant rats from each group， along with the levels of serum creatinine （Scr）， blood urea nitrogen （BUN），uric acid （UA）， and cystatin C （Cys-C）. The contents of superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， and 8-hydroxy-2′-deoxyguanosine （8-OHdG） in renal tissue， as well as the mRNA and protein expression levels of Sirt1 and PGC-1α， were also determined. Meanwhile， renal histopathological changes in rats from each group were evaluated using hematoxylin-eosin （HE） staining and periodic acid-Schiff （PAS） staining. RESULTS Compared with model group， L-pachymic acid group and H-pachymic acid group exhibited significant decreases in 24 h urine protein quantification， tail artery SBP， Scr， BUN， UA， Cys-C levels， glomerulosclerosis index score of renal tissue， renal tubular injury score， the percentage of PAS positive area， MDA and 8-OHdG （P＜0.05）. Conversely， the contents of SOD and GSH-Px， along with the mRNA and protein expression levels of Sirt1 and PGC-1α， were significantly increased （P＜0.05）. Moreover， these improvements were more pronounced in H-pachymic acid group （P＜0.05）. Compared with H-pachymic acid group， the aforementioned indicators in pregnant rats from the H-pachymic acid+EX527 group showed significant reversal （P＜0.05）. CONCLUSIONS Pachymic acid significantly ameliorates renal injury induced by PIH in rats， potentially through activation of the Sirt1/PGC-1α pathway.

ObjectiveTo establish a model that can quickly identify the aroma components in different parts of Nardostachys jatamansi， so as to provide a quality control basis for the market circulation and clinical use of N. jatamansi. MethodsHeadspace solid-phase microextraction-gas chromatography-mass spectrometry（HS-SPME-GC-MS） combined with Smart aroma database and National Institute of Standards and Technology（NIST） database were used to characterize the aroma components in different parts of N. jatamansi， and the aroma components were quantified according to relative response factor（RRF） and three internal standards， and the markers of aroma differences in different parts of N. jatamansi were identified by orthogonal partial least squares-discriminant analysis（OPLS-DA） and cluster thermal analysis based on variable importance in the projection（VIP） value >1 and P<0.01. The odor data of different parts of N. jatamansi were collected by Heracles Ⅱ Neo ultra-fast gas phase electronic nose， and the correlation between compound types of aroma components collected by the ultra-fast gas phase electronic nose and the detection results of HS-SPME-GC-MS was investigated by drawing odor fingerprints and odor response radargrams. Chromatographic peak information with distinguishing ability≥0.700 and peak area≥200 was selected as sensor data， and the rapid identification model of different parts of N. jatamansi was established by principal component analysis（PCA）， discriminant factor alysis（DFA）， soft independent modeling of class analogies（SIMCA） and statistical quality control analysis（SQCA）. ResultsThe HS-SPME-GC-MS results showed that there were 28 common components in the underground and aboveground parts of N. jatamansi， of which 22 could be quantified and 12 significantly different components were screened out. Among these 12 components， the contents of five components（ethyl isovalerate， 2-pentylfuran， benzyl alcohol， nonanal and glacial acetic acid，） in the aboveground part of N. jatamansi were significantly higher than those in the underground part（P<0.01）， the contents of β-ionone， patchouli alcohol， α-caryophyllene， linalyl butyrate， valencene， 1，8-cineole and p-cymene in the underground part of N. jatamansi were significantly higher than those in the aboveground part（P<0.01）. Heracles Ⅱ Neo electronic nose results showed that the PCA discrimination index of the underground and aboveground parts of N. jatamansi was 82， and the contribution rates of the principal component factors were 99.94% and 99.89% when 2 and 3 principal components were extracted， respectively. The contribution rate of the discriminant factor 1 of the DFA model constructed on the basis of PCA was 100%， the validation score of the SIMCA model for discrimination of the two parts was 99， and SQCA could clearly distinguish different parts of N. jatamansi. ConclusionHS-SPME-GC-MS can clarify the differential markers of underground and aboveground parts of N. jatamansi. The four analytical models provided by Heracles Ⅱ Neo electronic nose（PCA， DFA， SIMCA and SQCA） can realize the rapid identification of different parts of N. jatamansi. Combining the two results， it is speculated that terpenes and carboxylic acids may be the main factors contributing to the difference in aroma between the underground and aboveground parts of N. jatamansi.

19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

ObjectiveTo explore the effects of compatibility of Ephedrae Herba，Asari Radix et Rhizoma， and Aconiti Lateralis Radix Praeparata on the expression of type 2 innate lymphoid cells（ILC2s）-related factors in the lung of allergic rhinitis（AR）mice. MethodsAccording to the random number table method，fifty-four C57BL/6J mice were randomly divided into the following groups： Blank group，model group，Mahuang Fuzi Xixintang group，Asari Radix et Rhizoma and Aconiti Lateralis Radix Praeparata group，Ephedrae Herba and Asari Radix et Rhizoma group，Ephedrae Herba and Aconiti Lateralis Radix Praeparata group，Ephedrae Herba group，Aconiti Lateralis Radix Praeparata group， and Asari Radix et Rhizoma group （6 mice in each group）. Except the blank group，the other groups were subjected to intraperitoneal injection of ovalbumin（OVA）and intranasal challenge to induce AR. After the AR model was established，the mice in the blank group and the model group were given 0.2 mL·d^-1 normal saline by gavage，while those in the Mahuang Fuzi Xixintang group（2.31 g·kg^-1），Asari Radix et Rhizoma and Aconiti Lateralis Radix Praeparata group（1.54 g·kg^-1）， Ephedrae Herba and Asari Radix et Rhizoma group（1.16 g·kg^-1）， Ephedrae Herba and Aconiti Lateralis Radix Praeparata group（1.93 g·kg^-1），Ephedrae Herba group（0.77 g·kg^-1），Aconiti Lateralis Radix Praeparata group（1.16 g·kg^-1），and Asari Radix et Rhizoma group（0.39 g·kg^-1）were given corresponding medicine by gavage，with the treatment lasting for 14 consecutive days. The survival state of mice in each group was observed， and the levels of serum immunoglobulins E（IgE）after intranasal challenge were measured by enzyme-linked immunosorbent assay（ELISA）. The pathological changes of nasal and lung tissues were observed by hematoxylin-eosin（HE）staining. The expression of ILC2s in lung tissue of mice was detected by immunofluorescence（IF）. The mRNA expression of GATA binding protein 3（GATA3），retinoic acid receptor-related orphan receptor-α（RORα）， and inhibitor of DNA binding 2（ID2）in the lung tissue of mice was detected by quantitative real-time polymerase chain reaction（real-time PCR）. The levels of IgE，interleukin（IL）-4，IL-5， and IL-13 in serum were detected by ELISA. ResultsCompared with the blank group，the model group had poor survival state of mice and significantly increased serum IgE level after intranasal challenge（p<0.01）. Additionally，the mice in the model group showed a large amount of neutrophil infiltration in the mucosa of the posterior turbinate， obvious nasal mucosal bleeding and purulent secretion，shed epithelium， thickened bronchial wall，obvious intravascular hyperemia and edema，diffusion and infiltration of a large number of inflammatory cells，seriously damaged alveolar structure，and local lung consolidation. The model group also exhibited significantly increased expression of ILC2s in the lung tissue（P<0.01），increased mRNA expression of GATA3 and RORα，decreased mRNA expression of ID2（P<0.05，P<0.01），and increased levels of serum IgE， IL-4，IL-5，and IL-13（P<0.05，P<0.01）. Compared with the model group，the Mahuang Fuzi Xixintang group and the other medicine treatment groups showed improved survival state of mice， significantly reduced inflammatory cell infiltration in the nasal and lung tissues，a small amount of nasal mucosal bleeding，trachea wall thinning，and no hyperemia，edema， and nasal secretions. Furthermore， the expression of ILC2s in lung tissue was significantly decreased（P<0.01）. The mRNA expression level of GATA3 was decreased（P<0.05），especially in the Aconiti Lateralis Radix Praeparata group（P<0.01）. The expression mRNA levels of RORα were decreased only in the Ephedrae Herba and Aconiti Lateralis Radix Praeparata group and the Ephedrae Herba group（P<0.05）. The levels of serum IgE were decreased（P<0.05）， and IL-5 levels were significantly decreased（P<0.01）. IL-4 levels were significantly decreased in the groups except the Aconiti Lateralis Radix Praeparata group（P<0.01），and the level of IL-13 in the Mahuang Fuzi Xixintang group was decreased（P<0.05）. The levels of IL-13 in were significantly decreased in the Ephedrae Herba and Aconiti Lateralis Radix Praeparata group， Ephedrae Herba group， Aconiti Lateralis Radix Praeparata group， and Asari Radix et Rhizoma group（P<0.01）. ConclusionDifferent compatibility of Ephedrae Herba，Asari Radix et Rhizoma， and Aconiti Lateralis Radix Praeparata can reduce the inflammation of OVA-induced AR mice and has more advantages in reducing the secretion of IgE and IL-5. The compatibility of Ephedrae Herba and Aconiti Lateralis Radix Praeparata has the most advantage in reducing the mRNA expression of GATA3 and RORα to inhibit the expression of ILC2s and thus exert the anti-allergic effect，while the other compatibility has the extensive advantage in inhibiting the mRNA expression of GATA3.

ObjectiveTo explore the effects of compatibility of Ephedrae Herba，Asari Radix et Rhizoma， and Aconiti Lateralis Radix Praeparata on the expression of type 2 innate lymphoid cells（ILC2s）-related factors in the lung of allergic rhinitis（AR）mice. MethodsAccording to the random number table method，fifty-four C57BL/6J mice were randomly divided into the following groups： Blank group，model group，Mahuang Fuzi Xixintang group，Asari Radix et Rhizoma and Aconiti Lateralis Radix Praeparata group，Ephedrae Herba and Asari Radix et Rhizoma group，Ephedrae Herba and Aconiti Lateralis Radix Praeparata group，Ephedrae Herba group，Aconiti Lateralis Radix Praeparata group， and Asari Radix et Rhizoma group （6 mice in each group）. Except the blank group，the other groups were subjected to intraperitoneal injection of ovalbumin（OVA）and intranasal challenge to induce AR. After the AR model was established，the mice in the blank group and the model group were given 0.2 mL·d^-1 normal saline by gavage，while those in the Mahuang Fuzi Xixintang group（2.31 g·kg^-1），Asari Radix et Rhizoma and Aconiti Lateralis Radix Praeparata group（1.54 g·kg^-1）， Ephedrae Herba and Asari Radix et Rhizoma group（1.16 g·kg^-1）， Ephedrae Herba and Aconiti Lateralis Radix Praeparata group（1.93 g·kg^-1），Ephedrae Herba group（0.77 g·kg^-1），Aconiti Lateralis Radix Praeparata group（1.16 g·kg^-1），and Asari Radix et Rhizoma group（0.39 g·kg^-1）were given corresponding medicine by gavage，with the treatment lasting for 14 consecutive days. The survival state of mice in each group was observed， and the levels of serum immunoglobulins E（IgE）after intranasal challenge were measured by enzyme-linked immunosorbent assay（ELISA）. The pathological changes of nasal and lung tissues were observed by hematoxylin-eosin（HE）staining. The expression of ILC2s in lung tissue of mice was detected by immunofluorescence（IF）. The mRNA expression of GATA binding protein 3（GATA3），retinoic acid receptor-related orphan receptor-α（RORα）， and inhibitor of DNA binding 2（ID2）in the lung tissue of mice was detected by quantitative real-time polymerase chain reaction（real-time PCR）. The levels of IgE，interleukin（IL）-4，IL-5， and IL-13 in serum were detected by ELISA. ResultsCompared with the blank group，the model group had poor survival state of mice and significantly increased serum IgE level after intranasal challenge（p<0.01）. Additionally，the mice in the model group showed a large amount of neutrophil infiltration in the mucosa of the posterior turbinate， obvious nasal mucosal bleeding and purulent secretion，shed epithelium， thickened bronchial wall，obvious intravascular hyperemia and edema，diffusion and infiltration of a large number of inflammatory cells，seriously damaged alveolar structure，and local lung consolidation. The model group also exhibited significantly increased expression of ILC2s in the lung tissue（P<0.01），increased mRNA expression of GATA3 and RORα，decreased mRNA expression of ID2（P<0.05，P<0.01），and increased levels of serum IgE， IL-4，IL-5，and IL-13（P<0.05，P<0.01）. Compared with the model group，the Mahuang Fuzi Xixintang group and the other medicine treatment groups showed improved survival state of mice， significantly reduced inflammatory cell infiltration in the nasal and lung tissues，a small amount of nasal mucosal bleeding，trachea wall thinning，and no hyperemia，edema， and nasal secretions. Furthermore， the expression of ILC2s in lung tissue was significantly decreased（P<0.01）. The mRNA expression level of GATA3 was decreased（P<0.05），especially in the Aconiti Lateralis Radix Praeparata group（P<0.01）. The expression mRNA levels of RORα were decreased only in the Ephedrae Herba and Aconiti Lateralis Radix Praeparata group and the Ephedrae Herba group（P<0.05）. The levels of serum IgE were decreased（P<0.05）， and IL-5 levels were significantly decreased（P<0.01）. IL-4 levels were significantly decreased in the groups except the Aconiti Lateralis Radix Praeparata group（P<0.01），and the level of IL-13 in the Mahuang Fuzi Xixintang group was decreased（P<0.05）. The levels of IL-13 in were significantly decreased in the Ephedrae Herba and Aconiti Lateralis Radix Praeparata group， Ephedrae Herba group， Aconiti Lateralis Radix Praeparata group， and Asari Radix et Rhizoma group（P<0.01）. ConclusionDifferent compatibility of Ephedrae Herba，Asari Radix et Rhizoma， and Aconiti Lateralis Radix Praeparata can reduce the inflammation of OVA-induced AR mice and has more advantages in reducing the secretion of IgE and IL-5. The compatibility of Ephedrae Herba and Aconiti Lateralis Radix Praeparata has the most advantage in reducing the mRNA expression of GATA3 and RORα to inhibit the expression of ILC2s and thus exert the anti-allergic effect，while the other compatibility has the extensive advantage in inhibiting the mRNA expression of GATA3.

Purpose: Zinc finger protein 639 (ZNF639) is often found within the overlapping amplicon of PIK3CA, and previous studies suggest its involvement in the pathogenesis of esophageal and oral squamous cell carcinomas. However, its expression and significance in breast cancer remain uncharacterized. Methods: Immunohistochemical analysis of ZNF639 was performed using tissue microarrays.Functional studies, including colony formation, Transwell cell migration, and in vivo metastasis, were conducted on breast tumor cells with ZNF639 knockdown via small interfering RNA transfection. Results: Reduced ZNF639 immunoreactivity was observed in 82% of the breast cancer samples, independent of hormone receptor and human epidermal growth factor receptor 2 status. In multivariate Cox regression analyses, ZNF639 expression was associated with favorable survival outcomes, including recurrence-free survival (hazard ratio, 0.35; 95% confidence interval [CI], 0.14–0.89) and overall survival (hazard ratio, 0.41; 95% CI, 0.16– 1.05). ZNF639 knockdown increased clonogenicity, cell motility, and lung metastasis in NOD/ SCID mice. Following the ZNF639 knockdown, the expression of Snail1, vimentin, and C-C chemokine ligand 20 (CCL20) was upregulated, and the changes in cell phenotype mediated by ZNF639 were reversed by the subsequent knockdown of CCL20. Conclusion Low ZNF639 expression is a novel prognostic factor for recurrence-free survival in patients with breast cancer.

Purpose: Zinc finger protein 639 (ZNF639) is often found within the overlapping amplicon of PIK3CA, and previous studies suggest its involvement in the pathogenesis of esophageal and oral squamous cell carcinomas. However, its expression and significance in breast cancer remain uncharacterized. Methods: Immunohistochemical analysis of ZNF639 was performed using tissue microarrays.Functional studies, including colony formation, Transwell cell migration, and in vivo metastasis, were conducted on breast tumor cells with ZNF639 knockdown via small interfering RNA transfection. Results: Reduced ZNF639 immunoreactivity was observed in 82% of the breast cancer samples, independent of hormone receptor and human epidermal growth factor receptor 2 status. In multivariate Cox regression analyses, ZNF639 expression was associated with favorable survival outcomes, including recurrence-free survival (hazard ratio, 0.35; 95% confidence interval [CI], 0.14–0.89) and overall survival (hazard ratio, 0.41; 95% CI, 0.16– 1.05). ZNF639 knockdown increased clonogenicity, cell motility, and lung metastasis in NOD/ SCID mice. Following the ZNF639 knockdown, the expression of Snail1, vimentin, and C-C chemokine ligand 20 (CCL20) was upregulated, and the changes in cell phenotype mediated by ZNF639 were reversed by the subsequent knockdown of CCL20. Conclusion Low ZNF639 expression is a novel prognostic factor for recurrence-free survival in patients with breast cancer.

Purpose: Zinc finger protein 639 (ZNF639) is often found within the overlapping amplicon of PIK3CA, and previous studies suggest its involvement in the pathogenesis of esophageal and oral squamous cell carcinomas. However, its expression and significance in breast cancer remain uncharacterized. Methods: Immunohistochemical analysis of ZNF639 was performed using tissue microarrays.Functional studies, including colony formation, Transwell cell migration, and in vivo metastasis, were conducted on breast tumor cells with ZNF639 knockdown via small interfering RNA transfection. Results: Reduced ZNF639 immunoreactivity was observed in 82% of the breast cancer samples, independent of hormone receptor and human epidermal growth factor receptor 2 status. In multivariate Cox regression analyses, ZNF639 expression was associated with favorable survival outcomes, including recurrence-free survival (hazard ratio, 0.35; 95% confidence interval [CI], 0.14–0.89) and overall survival (hazard ratio, 0.41; 95% CI, 0.16– 1.05). ZNF639 knockdown increased clonogenicity, cell motility, and lung metastasis in NOD/ SCID mice. Following the ZNF639 knockdown, the expression of Snail1, vimentin, and C-C chemokine ligand 20 (CCL20) was upregulated, and the changes in cell phenotype mediated by ZNF639 were reversed by the subsequent knockdown of CCL20. Conclusion Low ZNF639 expression is a novel prognostic factor for recurrence-free survival in patients with breast cancer.

Mitochondria are abundant in hepatocytes and play an important role in the normal operation of the liver. Mitochondrial division/fusion is two biological processes that maintain the dynamic balance of mitochondria， and it is closely associated with the change of cell function and the development and progression of diseases. Balance of mitochondrial division/fusion is of key significance in the treatment of many diseases. Recent studies have shown that abnormal mitochondrial division/fusion plays a significant role in fatty liver disease， hepatitis， liver fibrosis， and liver cancer， which are the four stages of the progression of liver diseases， and the therapeutic targets based on the regulation of such abnormalities are constantly being identified. By reviewing the role of mitochondrial division/fusion in different stages of liver disease， this article further demonstrates the role of mitochondrial division/fusion mechanism in chronic liver diseases and also provides a scientific basis for more ideas on the treatment， remission or even reversal of liver disease progression based on mitochondrial division/fusion.

Neuronal reprogramming is an innovative technique for converting non-neuronal somatic cells into neurons that can be used to replace lost or damaged neurons, providing a potential effective therapeutic strategy for central nervous system (CNS) injuries or diseases. Transcription factors have been used to induce neuronal reprogramming, while their reprogramming efficiency is relatively low, and the introduction of exogenous genes may result in host gene instability or induce gene mutation. Therefore, their future clinical application may be hindered by these safety concerns. Compared with transcription factors, small-molecule compounds have unique advantages in the field of neuronal reprogramming, which can overcome many limitations of traditional transcription factor-induced neuronal reprogramming. Here, we review the recent progress in the research of small-molecule compound-mediated neuronal reprogramming and its application in CNS regeneration and repair.
Humans ; Cellular Reprogramming/drug effects* ; Neurons/cytology* ; Animals ; Transcription Factors ; Small Molecule Libraries/pharmacology* ; Nerve Regeneration