Traditional Formula Research Articles

Liang-Ge-San protects against viral infection-induced acute lung injury through inhibiting α7nAChR-mediated mitophagy.

Acute lung injury (ALI) is the main cause of death in clinical respiratory virus infection. Liang-Ge-San (LGS), a famous traditional Chinese formula, has been proved to be effective in treating ALI caused by lipopolysaccharide. However, the effects of LGS on ALI induced by viral infections remain uncertain. To investigate the effect and mechanism of action of LGS on viral infection-induced ALI. The inhibitory effects of LGS on virus-induced inflammation in vitro were evaluated by qRT-PCR and ELISA. The protein expression of α7nAChR was examined by Western blotting. α7nAChR was inhibited by the transfection of siRNA or methyllycaconitine citrate (MLA, an α7nAChR inhibitor) to investigate the role of α7nAChR in the anti-inflammatory effect of LGS. Adoptive culture and co-culture systems of macrophages RAW264.7 and alveolar epithelial cells MLE-12 were established to mimic their interaction. Western blotting, immunofluorescence, flow cytometry and transmission electron microscopy were used to examine the effects of LGS on mitophagy inhibition. In vivo, ALI mouse models induced by SARS-CoV-2, H1N1 or Poly(I:C) infection were established to explore the therapeutic effect and mechanism of LGS. LGS reduced the release of IL-6, TNF-α and IL-1β and increased the expression of α7nAChR in virus-infected RAW264.7 cells. The blockage of α7nAChR counteracted the anti-inflammatory effect of LGS. Moreover, LGS significantly inhibited autophagy in MLE-12 cells induced by Poly(I:C) in adoptive culture and co-culture systems of RAW264.7 and MLE-12 cells, which could be attenuated after the inhibition of α7nAChR in RAW264.7 cells by decreasing the secretion of IL-6, TNF-α and IL-1β. Further study showed that LGS suppressed TNF-α-induced mitochondrial damage and mitophagy by inhibiting the generation of ROS in MLE-12 cells. In vivo, LGS significantly prolonged the survival time, alleviated pathological injury and acute inflammation of ALI mice induced by SARS-CoV-2, H1N1 or Poly(I:C) infection which were associated with the inhibition of α7nAChR-mediated mitophagy. This study first demonstrates that LGS inhibits virus infection-induced inflammation in RAW246.7 cells by increasing the expression of α7nAChR, thereby inhibiting mitophagy induction in MLE-12 cells to alleviate ALI. This work indicates that LGS may serve as a candidate drug for treating ALI/ARDS caused by viral infection.

Jia Wei Qingxin Lotus Seed Drink ameliorates epithelial mesenchymal transition injury in diabetic kidney disease via inhibition of JMJD1C/SP1/ZEB1 signaling pathway

BackgroundDiabetic kidney disease (DKD) is one of the most common microvascular complications in patients with diabetes mellitus. In this condition, renal tubular epithelial mesenchymal transition (EMT) is an important factor accelerating the progression of DKD and a major cause of renal fibrosis and end-stage renal disease. However, the therapeutic effect is unsatisfactory because of the lack of effective drugs. Jia Wei Qingxin Lotus Seed Drink (QISD) is a traditional Chinese medicine compound formula that has shown to be effective in the clinical treatment of DKD. However, the potential of QISD in DKD-EMT treatment has yet to be fully explored. PurposeThis study aimed to investigate the role of QISD in ameliorating DKD-EMT injury and its mechanism. MethodsThe active ingredients of QISD were identified via ultra-performance liquid chromatography-mass spectrometry/mass spectrometry (UHPLC-MS/MS). A DKD mouse model was constructed by high-fat diet feeding and intraperitoneal injection of STZ (60 mg/kg), and QISD (14.46, 28.92, and 57.84 g/kg/day) was administered by gavage for 12 consecutive weeks. Dapagliflozin (1 mg/kg/d) was used as a positive control. Renal pathological damage was observed by HE, PAS, and Masson staining. The expression levels of EMT-related proteins and pathway proteins were detected via immunohistochemistry, RT-qPCR, and western blot. In in vitro experiments, EMT injury was induced in human kidney tubular epithelial cells (HK-2) by using lipopolysaccharide (LPS). A combination of CCK8 assay, wound healing assay, small-molecule inhibitor intervention, and overexpression lentiviral transfection was used to investigate the effects of QISD on cell migration ability, adhesion ability, fibrotic factor formation, and mesenchymal properties. ResultsAnimal experiments showed that QISD improved blood glucose, body weight, symptoms of excessive drinking and eating, and renal pathological injury in mice, reduced extracellular matrix deposition, delayed renal EMT injury, and inhibited the activation of the histone demethylase JMJD1C. UHPLC-MS/MS and molecular docking indicated that baicalin, wogonoside, oroxylin A-7-O-β-D-glucuronide, and glulisine A found in QISD could bind to JMJD1C. The ameliorating effect of QISD on DKD-EMT injury might be related to JMJD1C. The improvement of DKD-EMT injury by QISD was accompanied by the reduction of SP1 and ZEB1 expression. The SP1 overexpression not only reversed the therapeutic effect of JIB-04, an inhibitor of JMJD1C, on DKD-EMT but also exacerbated the expression of ZEB1 and downstream EMT-related factors. Thus, QISD might affect the expression of the epithelial marker E-cadherin by inhibiting the JMJD1C/SP1/ZEB1 signaling pathway, consequently preventing the transformation of epithelial cells to mesenchymal cells and ameliorating DKD-EMT injury. ConclusionThis study was the first to demonstrate that QISD might ameliorate DKD-EMT injury by inhibiting the JMJD1C/SP1/ZEB1 signaling pathway. These findings provide strong pharmacologic evidence for the clinical use of QISD in the treatment of DKD.

Mechanism of Action of Tongjiang Mixture for Treating Reflux Esophagitis: A Study Using Serum Pharmacochemistry and Network Pharmacology.

Tongjiang Mixture (TJM) is a traditional Chinese formula for treating reflux esophagitis (RE). Nevertheless, its active ingredients and potential pharmacological mechanisms are not yet clearly elucidated. This study will identify the active ingredients of TJM using serum pharmacochemistry and to elucidate the mechanism on RE through network pharmacology. The blood-borne ingredients of TJM are identified by the Ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometer. Subsequently, a "compound-target-disease" network is established and obtained core targets associated with TJM and RE. Then, the potential signaling pathways are forecasted through the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Finally, the rat model of RE is established to verify the results predicted by network pharmacology through animal experiments. Fifteen blood-borne ingredients of TJM are identified, with eight active ingredients-namely Tangeretin, Tricin, Palmati, Berberine, Limonin, Evodiamine, Tetrahydropalmatine and Rutecarpine - making significant contributions to its efficacy. Moreover, TJM is predicted to act on 193 targets related to RE, involving AKT1, HSP90AA1, PIK3CA, and other targets, which enriches mainly in PI3K/AKT /NF-κB signaling. Additionally, TJM can alleviate inflammation of the esophageal mucosa, reduce pathological damage, and increase gastric pH. It can downregulate PI3K, AKT, and NF-κB mRNA transcription levels and reduce the protein expression of PI3K, AKT, and NF-κB. Furthermore, it can inhibit the overproduction of IL-6, TNF-α and IL-17. TJM can alleviate immune-inflammatory responses and ameliorate RE by restraining the PI3K/AKT pathway and its downstream NF-κB.

Wuzi Yanzong Decoction Ameliorates Oligoasthenozoospermia by Up-Regulating Methyltransferase and Increasing Spata, Bcl, and Pik3 Series Genes Methylation Level.

Wuzi Yanzong decoction (WZYZD) belongs to the traditional formula for treating male infertility caused by oligoasthenozoospermia (OLI). This research aims to elucidate the therapeutic substance basis and potential pharmacological mechanisms of WZYZD in treating OLI. A total of 52 chemical ingredients were identified from WZYZD. HE and TUNEL staining demonstrated that WZYZD can markedly alleviate OLI. Immunofluorescence analysis showed that WZYZD can significantly increase the expression levels of DNMT3 A, PIWIL1, SETDB1, and PRMT5. Methyl capture sequencing proved that WZYZD can markedly upregulate the methylated level of Spata, Bcl, and Pik3 series genes. Network pharmacology analysis proved that WZYZD can ameliorate OLI through BCL-2 and PI3 K-AKT signaling pathways. The immunofluorescence assay of BCL-2 and SPATA18 proved the aforementioned results. The potential mechanism of WZYZD in treating OLI mainly involved recruiting methyltransferase DNMT3 A, PIWIL1, PRMT5, and SETDB1 and increasing the methylation degree of Spata, Bcl, and Pik3 series genes.

Single Well Production Prediction Model of Gas Reservoir Based on CNN-BILSTM-AM

In the prediction of single-well production in gas reservoirs, the traditional empirical formula of gas reservoirs generally shows poor accuracy. In the process of machine learning training and prediction, the problems of small data volume and dirty data are often encountered. In order to overcome the above problems, a single-well production prediction model of gas reservoirs based on CNN-BILSTM-AM is proposed. The model is built by long-term and short-term memory neural networks, convolutional neural networks and attention modules. The input of the model includes the production of the previous period and its influencing factors. At the same time, the fitting production and error value of the traditional gas reservoir empirical formula are introduced to predict the future production data. The loss function is used to evaluate the deviation between the predicted data and the real data, and the Bayesian hyperparameter optimization algorithm is used to optimize the model structure and comprehensively improve the generalization ability of the model. Three single wells in the Daniudi D28 well area were selected as the database, and the CNN-BILSTM-AM model was used to predict the single-well production. The results show that compared with the prediction results of the convolutional neural network (CNN) model, long short-term memory neural network (LSTM) model and bidirectional long short-term memory neural network (BILSTM) model, the error of the CNN-BILSTM-AM model on the test set of three experimental wells is reduced by 6.2425%, 4.9522% and 3.0750% on average. It shows that on the basis of coupling the empirical formula of traditional gas reservoirs, the CNN-BILSTM-AM model meets the high-precision requirements for the single-well production prediction of gas reservoirs, which is of great significance to guide the efficient development of oil fields and ensure the safety of China’s energy strategy.

Taohe Chengqi decoction improves diabetic cognitive dysfunction by alleviating neural stem cell senescence through HIF1α-driven metabolic signaling

ObjectiveType 2 diabetes mellitus (T2DM) is characterized by numerous long-term complications, in which progressive cognitive decline represents a significant risk factor for dementia and other neurodegenerative disorders. Taohe Chengqi decoction (THCQ) is a common traditional Chinese formula for treating T2DM; however, the neuroprotective effect of THCQ on diabetes-associated cognitive dysfunction remains unclear. Hence, the present study investigated the therapeutic effects of THCQ on cognitive impairment associated with T2DM and elucidated the underlying mechanisms. MethodsA stable high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM mouse model was established and received intragastrical THCQ administration. Blood and tissue samples were investigated for biochemical parameters and neuropathology, whereas hippocampal tissue underwent transcriptome analyses and the role of neural stem cell (NSC) senescence was detected both in vivo and in vitro. Network pharmacology analysis and subsequent primary NSC experiments were conducted to explore the involvement of the HIF1α signaling pathway in THCQ-mediated hippocampal NSC senescence. Furthermore, a lentivirus vector overexpressing HIF1α was used to verify the THCQ potential therapeutic effects on HIF1α/PDKs metabolic signaling that influenced NSC senescence. ResultsTHCQ alleviated cognitive dysfunction and metabolic abnormalities in HFD/STZ mice, and relieved hippocampal neurodegeneration. Transcriptome analyses and validation experiments revealed THCQ-induced neuroprotective effects by targeting high glucose-mediated hippocampal neuropathy and NSC senescence. Bioinformatic analysis indicated that HIF1α signaling played a significant role in THCQ therapeutic outcomes; while HIF1α overexpression impaired the effects of THCQ on high glucose-induced metabolic disorders and NSC senescence. ConclusionThe present study demonstrated that THCQ improved diabetic cognitive dysfunction and hippocampal neurogenesis, the effects of which were mainly attributed to the restoration of metabolic homeostasis and inhibition of NSC senescence through HIF1α signaling. Our results provide novel insights into the therapeutic framework for diabetic neuropathy and indicate that THCQ might be a promising candidate for the management of T2DM-related cognitive disorders.

Anthropometric and Demographic Features Affect the Interpretation of Cerebrospinal Fluid Biomarkers in Patients with Different Dementia Syndromes and Cognitively Healthy Adults.

Clinical distinction between dementia with Lewy bodies (DLB) and late-onset Alzheimer's disease (AD) is difficult, while several features might affect the analyses of biomarkers. This study aimed to verify associations of anthropometric and demographic features with cerebrospinal fluid biomarkers, their ratios, and restructured traditional regression formulas in patients with DLB and AD, as well as in cognitively healthy controls. Consecutive outpatients with DLB were paired with outpatients with AD according to sex, dementia stage, and cognitive status, and with controls according to sex and age to investigate associations of sex, age, dementia duration, total sleep time, body mass index, alcohol use, smoking, sanitation, and APOE-ε4 alleles on the measurement of cerebrospinal fluid α-synuclein, biomarker ratios, and restructured traditional regression formulas involving amyloid-β (Aβ42,Aβ40,Aβ38), tau, and phospho-tau Thr181. Overall, 81 participants were included with DLB (n = 27;11 APOE-ε4 +) or AD (n = 27;12 APOE-ε4 +), and controls (n = 27;4 APOE-ε4 +); two thirds were women. Cerebrospinal fluid evidence of amyloidosis and tauopathy was more prevalent among women with AD, while Aβ42/Aβ38 could also discriminate men with DLB from men with AD. Restructured traditional regression formulas had higher diagnostic accuracy for women with AD. Aging, higher body mass index, and APOE-ε4 alleles were associated with amyloidosis in DLB, while only in AD were higher body mass index associated with lower tau pathology load, and more alcohol use associated with higher phospho-tau Thr181/Aβ42. These findings confirm the effects of anthropometric and demographic features on cerebrospinal fluid biomarkers, and also differences in aberrant amyloidosis and tauopathy between DLB and AD.

Wu Mei Wan suppresses colorectal cancer stemness by regulating Sox9 expression via JAK2/STAT3 pathway

Ethnopharmacological relevanceWu Mei Wan (WMW) is a traditional Chinese herbal formula with a long-standing history in Chinese medicine, valued for its therapeutic properties. However, its potential anti-cancer effects, especially against colorectal cancer (CRC), have not been fully elucidated. Aim of the studyThis study aims to investigate the effects of WMW on colorectal cancer stemness and to elucidate the underlying molecular mechanisms, focusing on the modulation of Sox9 expression via the JAK2/STAT3 signaling pathway. Materials and methodsWMW was prepared and analyzed using UPLC-MS to identify their main components. To study the therapeutic effects of WMW, AOM/DSS-induced CRC mouse models were established. A comprehensive suite of experimental techniques, including in vivo imaging, cell culture, transfection, CCK-8 assays, colony formation assays, wound healing assays, cell migration assays, Western blotting, dot blot analysis, RT-qPCR, immunohistochemistry, cell transcriptome sequencing, and gene set enrichment analysis, were utilized to explore the pharmacological effects and mechanisms of WMW. ResultsWMW significantly inhibited CRC cell viability, proliferation, invasion, and migration in vitro. Mechanistically, WMW suppressed CRC stemness by downregulating Sox9 expression through the JAK2/STAT3 signaling pathway. Additionally, the regulation of methylation and demethylation mediated by TET1 and DNMT3a expression was directly associated with the JAK2/STAT3 pathway's modulation of Sox9 expression. In vivo, WMW treatment attenuated CRC progression and metastasis with minimal toxicity. ConclusionThese findings suggest that WMW exerts potent anti-CRC stemness effects by regulating Sox9 via the JAK2/STAT3 signaling pathway, underscoring its potential as a promising therapeutic agent for CRC treatment.

Glycyrrhizic acid and patchouli alcohol in Huoxiang Zhengqi attenuate intestinal inflammation and barrier injury via regulating endogenous corticosterone metabolism mediated by 11β-HSD1

Ethnopharmacological relevanceUlcerative colitis (UC), a chronic inflammatory bowel disease, has become a significant public health challenge due to the limited effectiveness of available therapies. Huoxiang Zhengqi (HXZQ), a well-established traditional Chinese formula, shows potential in managing UC, as suggested by clinical and pharmacological studies. However, the active components and mechanisms responsible for its effects remain unclear. Aim of studyThis study aimed to identify the bioactive components of HXZQ responsible for its therapeutic effects on UC and to elucidate their underlying mechanisms. Materials and methodsThe effect of HXZQ against dextran sodium sulfate (DSS)-induced colitis was investigated. Ingredients in HXZQ were characterized and analyzed in colitic mice using liquid chromatography–mass spectrometry (LC-MS) and gas chromatography–mass spectrometry (GC-MS). In vitro, biological activity of compounds was assessed using lipopolysaccharide (LPS)-induced Ana-1 cells and bone marrow-derived macrophages (BMDMs), tumor necrosis factor-alpha (TNF-α)-induced Caco-2 cells, and isolated intestinal crypts from colitic mice. These results were confirmed in vivo. The targets of the components were identified through bioinformatics analysis and validated via molecular docking, enzyme inhibition assays, and in vivo experiments. Hematoxylin and eosin (HE) staining, periodic acid-Schiff (PAS) staining, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), western blotting, and quantitative real-time polymerase chain reaction (qPCR) were employed to confirm the pharmaceutical effects. ResultsA clinical equivalent dose of HXZQ (2.5 mL/kg) effectively treated DSS-induced colitis. A total of 113 compounds were identified in HXZQ, with 35 compounds detected in colitic mice. Glycyrrhizic acid (GA) and patchouli alcohol (PA) emerged as key contributors to the anti-colitic effects of HXZQ. Further investigation revealed that HXZQ and its active components decreased the levels of pro-inflammatory cytokines TNF-α, interleukin-1β (IL-1β), and interleukin-6 (IL-6) in colon, likely by inhibiting nuclear factor kappa-B (NF-κB) signaling pathway. This inhibition indirectly activated the intestinal farnesoid X receptor (FXR) signaling pathway, correcting bile acid imbalances caused by colitis. Additionally, these components significantly enhanced the expression of tight junction proteins ZO-1 and Occludin, as well as the adhesion protein E-cadherin, and reduced goblet cell loss, thereby repairing intestinal barrier injury. Mechanistically, GA and PA were found to inhibit 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) activity, leading to increased local active corticosterone levels in the intestine to exert anti-inflammatory effects. Notably, the inhibition of 11β-HSD1 with the selective inhibitor BVT2733 (BVT) ameliorated colitis in mice. ConclusionsHXZQ exhibits therapeutic effects on UC, primarily through GA and PA inhibiting 11β-HSD1. This suggests new natural therapy approaches for UC and positions 11β-HSD1 as a potential target for colitis treatment.

The identification and correction of pseudohypercalcemia.

We found that a subset of patients with monoclonal gammopathy exhibited hypercalcemia without apparent causes or clinical manifestations In a cohort of 289 monoclonal gammopathy patients, 2.4% presented with such atypical hypercalcemia, with one notable case exhibiting normal ionized calcium levels, suggesting the presence of pseudohypercalcemia. The aim of this study is to elucidate the factors contributing to pseudohypercalcemia in monoclonal gammopathy and to develop a novel globulin-corrected calcium formula for clinical application. This observational study enrolled 110 monoclonal gammopathy patients from our center. An additional 33 patients were recruited to validate the newly proposed formula. Univariate analysis identified potential risk factors. And multivariate logistic regression identified definitive influential factors. The determined influential factors were utilized to develop a formula by multiple linear regression, which was validated by a paired t-test and the Youden index. This study found that globulin was a risk factor for pseudohypercalcemia. It revealed that pseudohypercalcemia should be considered in patients with globulin levels ≥61 g/L (P=0.014). Both albumin and globulin were confirmed as independent factors associated with bound calcium. Given that, we developed a formula to correct ionized calcium levels, which was consistent with ionized calcium tested by blood gas analysis. The diagnostic accuracy of the new formula (Youden index is 0.906) is better than the traditional formula (Youden index is 0.906). Interestingly, all monoclonal immunoglobulin types, except for light chains, showed an equal propensity to develop pseudohypercalcemia (P=0.306). It also showed a linear correlation between IgA, IgG, and IgM and bound calcium. This study confirmed that elevated globulin affects serum total calcium and offered the threshold of globulin ≥ 61 g/L in the differential diagnosis of peudohypercalcemia from hypercalcemia. The new formula based on albumin and globulin was developed, which was verified to be better than the traditional formula for correctly diagnosing hypercalcemia. In addition, we found that neither light chains nor heavy chains of monoclonal immunoglobulin alone can result in pseudohypercalcemia.

A Novel Robust Position Integration Optimization-Based Alignment Method for In-Flight Coarse Alignment.

In-flight alignment is a critical milestone for inertial navigation system/global navigation satellite system (INS/GNSS) applications in unmanned aerial vehicles (UAVs). The traditional position integration formula for in-flight coarse alignment requires the GNSS velocity data to be valid throughout the alignment period, which greatly limits the engineering applicability of the method. In this paper, a new robust position integration optimization-based alignment (OBA) method for in-flight coarse alignment is presented to solve the problem of in-flight alignment under a prolonged ineffective GNSS. In this methodology, to achieve a higher alignment accuracy in case the GNSS is not effective throughout the alignment period, the integration of GNSS velocity into the local-level navigation frame is replaced by the GNSS position in the Earth-centered, Earth-fixed frame, which avoids the need for complete GNSS velocity data. The simulation and flight test results show that the new robust position integration method proposed in this paper achieves higher stability and robustness than the conventional position integration OBA method and can achieve an alignment accuracy of 0.2° even when the GNSS is partially time-invalidated. Thus, this greatly extends the application of the OBA method for in-flight alignment.

Traditional Chinese herbal formula, Fuzi-Lizhong pill, produces antidepressant-like effects in chronic restraint stress mice through systemic pharmacology

Ethnopharmacological relevanceFuzi-Lizhong pill (FLP) is a well-validated traditional Chinese medicine (TCM) formula that has long been used in China for gastrointestinal disease and adjunctive therapy for depression. In our previous study, we reported that the principal herb of FLP, Aconitum carmichaelii Debx. (Fuzi), exhibits antidepressant-like effects. However, there have been no reports on whether FLP produces antidepressant-like effects and its potential molecular mechanisms. Aim of the studyWe aim to demonstrate the antidepressant-like effects of FLP in chronic restraint stress (CRS) mice and to explore the associated molecular mechanisms. Materials and methodsThe active components and probable molecular targets of FLP, as well as the targets related to depression, were identified through network pharmacology. A protein-protein interaction (PPI) network was generated using the overlapping targets, followed by the visualization as well as identification of the core targets associated with the antidepressant-like action of FLP. Subsequently, KEGG and GO enrichment analyses were conducted. UHPLC-MS/MS was employed to further detect the active compounds in FLP. Molecular docking was applied to assess the connections between the active components as well as the core targets. The efficacy of FLP in treating depression and its molecular mechanisms were examined using western blotting, ELISA, 16S rRNA sequencing, HE staining, Nissl staining, and Golgi-Cox staining in a CRS-induced mouse model. ResultsNetwork pharmacology and UHPLC-MS/MS analyses indicated that the active compounds of FLP comprised taraxerol, songorine, neokadsuranic acid B, ginkgetin, hispaglabridin B, quercetin, benzoylmesaconine and liquiritin. KEGG pathway analysis implicated that the PI3K/Akt/mTOR as well as MAPK signaling pathways are closely related to the therapeutic effects of FLP on depression. Molecular docking analysis demonstrated that the main components of FLP bind to PI3K, AKT, mTOR, BDNF and MAPK. FLP significantly decreased immobility in mice that were elevated by CRS in the FST and the TST. FLP also significantly increased sucrose preference in mice after CRS in the SPT. FLP upregulated proteins associated with BDNF-TrkB and PI3K/Akt/mTOR signaling and downregulated proteins associated with MAPK signaling. Serum levels of CORT, IL-6, IL-1β, and TNF-α in CRS mice were significantly decreased following treatment with FLP. In addition, FLP ameliorated CRS-induced gut microbiota dysbiosis as demonstrated by 16S rRNA sequencing analysis. FLP ameliorated CRS-induced intestinal inflammation and neuronal damage. Finally, antidepressant-like effects and concomitant increases in dendritic spine density induced by FLP administration were also reduced after rapamycin treatment. ConclusionThese results demonstrate that FLP has antidepressant-like effects in mice exposed to CRS that involve activation of the PI3K/Akt/mTOR signaling pathway, increase in spinogenesis, inhibition of the MAPK signaling pathway, decrease in inflammation, and amelioration of gut microbiota dysbiosis. These findings provide novel evidence for the clinical application of FLP on depression.

Zuogui Wan modulates macrophage polarization and promotes osteogenic differentiation through regulation of CD51-positive bone marrow mesenchymal stem cells

Background Zuogui Wan (ZGW) is a traditional herbal formula used to treat chronic kidney and bone diseases. Previous research has shown that ZGW slows down the aging process of bone marrow mesenchymal stem cells (BMSCs) and improves bone metabolism. However, its role in treating postmenopausal osteoporosis (PMOP) has not yet been fully investigated. Therefore, we investigated the therapeutic effects of ZGW and its potential mechanisms in an ovariectomy (OVX)-induced osteoporosis rat model. Results We observed significant improvements in bone loss and the osteoporotic phenotype in OVX rats treated with ZGW. These findings were confirmed with micro-computed tomography (micro-CT) and histomorphological analysis. We also discovered that ZGW reversed the macrophage imbalance, which in turn inhibited osteoclast differentiation and bone resorption. Furthermore, RNA-Seq results revealed the active expression of CD51 in BMSCs before and after ZGW therapy, which is associated with macrophage polarization and osteoblastic differentiation. The results also showed that ZGW decreased CD51 + BMSCs levels, which is closely related to the inhibition of osteoblast differentiation and promotion of osteoclast resorption. Conclusions Our study demonstrated that ZGW may improve postmenopausal osteoporosis by restoring macrophage polarization and down-regulating CD51 + BMSCs. In addition, ZGW promoted osteoblast formation and inhibited osteoclast resorption.

A New Intraocular Lens Power Formula Integrating an Artificial Intelligence-Powered Estimation for Effective Lens Position Based on Chinese Eyes.

To develop and evaluate a new intraocular lens (IOL) formula based on Chinese eyes. A training dataset of 709 eyes undergoing uneventful cataract surgery was used to train the algorithm for effective lens position estimation. The algorithm was then integrated with Gaussian optics to develop the new IOL formula (Jin-AI). From the same center, 177 eyes served as an internal test dataset. An independent dataset of 557 eyes served as an external test dataset. The standard deviation (SD) of prediction errors was compared among the Jin-AI formula, traditional third-generation formulas (SRK/T, Holladay 1, Hoffer Q), and newer generation formulas (Kane, Barrett Universal II [BUII], Hill-radial basis function [RBF] 3.0, and PEARL-DGS). In the internal test dataset, the Jin-AI formula showed the lowest SD (0.25 D), followed by the BUII (0.31 D), Kane (0.33 D), and PEARL-DGS (0.33 D) formulas. In the external test dataset, the Jin-AI, Kane, and PEARL-DGS formulas had the lowest SD (0.38 D), followed by the BUII (0.39 D), Hill-RBF 3.0 (0.39 D), SRK/T (0.45 D), Holladay 1 (0.48 D), and Hoffer Q (0.48 D) formulas. The SD of the Jin-AI formula was significantly lower than the third-generation formulas and comparable to the four newer generation formulas. Predictive accuracy of the Jin-AI formula was similar to the newer generation formulas across all axial length, keratometry, and anterior chamber depth ranges. The new formula has exhibited good performance in predicting postoperative refractions. Its overall predictive accuracy was better than the third-generation formulas and comparable to the newer generation ones. The Jin-AI formula could be a reliable alternative for IOL power calculation in Chinese.

Experimental Study of Bedform Development Characteristics and Their Effects on Sediment Transport

Bedforms are complex and varied features on riverbeds created by the interaction between flow and sediment particles. Bedform evolution is crucial for understanding sediment transport, bed resistance, and the ecological environment of rivers. In this study, a series of movable-bed dune experiments were conducted utilizing advanced 3D topographic laser scanning technology to precisely measure the 2D and 3D dune bedforms under various conditions. This enabled the detailed analysis of the bedform parameters, including the dune length and height, the crest height, and the trough depth. Furthermore, this study examined the relationship between bed resistance and dune morphology and investigated how the intensity of bedload transport affects bed resistance. The findings indicate that bedload mass transport on the riverbed significantly contributes to increased bed resistance. Given the limitations of the traditional bedload transport rate formulas for dune bedforms, this research introduces a new formula derived from the experimental data. The accuracy of this formula was confirmed using the nonlinear least squares method. Our study enhances the accuracy of sediment transport predictions and provides scientific support for river management and engineering practices.

Xihuang pill suppresses breast cancer malignancy by inhibiting TGF-β signaling and acquires chemotherapy benefits

Ethnopharmacological relevanceBreast cancer (BC) has an extremely high global incidence rate. The Xihuang pill (XHP), a traditional Chinese formula, originates from Hongxu Wang's “Life-Saving Manual of Diagnosis and Treatment of External Diseases” written during the Qing Dynasty. In this book, XHP, was first suggested as an anticancer treatment for BC. However, the regulatory mechanism of XHP on BC requires further investigated. Aim of the studyTo assess the effects of XHP on BC and elucidate the underlying associated signaling network. Materials and methodsThe influence of XHP on cellular viability, proliferation, and apoptosis of MDA-MB-231 and BT-549 cells were examined. The ability to metastasize was evaluated using Transwell invasion and wound healing tests. Western blotting was used to examine the epithelial-mesenchymal transition (EMT) markers expression. RNA sequencing and bioinformatic analysis were utilized to investigate the regulation mechanism of XHP. A subcutaneous tumor model was developed to study the tumor-inhibitory effects of XHP or/and Doxorubicin (Dox) on BALB/c nude mice, and the EMT marker levels in tumor tissues were determined using immunohistochemical labeling. ResultsXHP demonstrated anticancer effects on BC cells by suppressing cell proliferation, inducing cellular apoptosis, and inhibiting EMT progression. XHP may regulate the EMT via the TGF-β axis, as shown by RNA sequencing and Western blotting analysis. Furthermore, the combination of XHP and Dox had a stronger therapeutic effect on BC cell proliferation, apoptosis, and metastasis in both cellular and animal models. ConclusionsWe were the first to reveal that XHP abrogated EMT progression via modulating the TGF-β axis. Furthermore, the combination therapy of XHP and Dox presents a promising novel therapeutic candidate for BC patients.

Shen-Bai-Jie-Du decoction suppresses the progression of colorectal adenoma to carcinoma through regulating gut microbiota and short-chain fatty acids

BackgroundShen-Bai-Jie-Du decoction (SBJDD), a traditional Chinese herb formula developed based on evidence-based medicine, is efficacy to reduce the recurrence and carcinogenesis of colorectal adenoma. However, the mechanism of SBJDD to treat colorectal adenoma remains unclear. The present study aims to investigate the efficacy and mechanism of SBJDD on colorectal adenoma carcinogenesis from the aspects of regulating gut microbiota and short-chain fatty acids (SCFAs).MethodsTwenty-one patients diagnosed with colorectal adenoma were recruited in the study and required to take SBJDD for four consecutive weeks. Analysis of gut microbiota was conducted using 16S rRNA gene amplicon sequencing, while levels of SCFAs in fecal and serum samples were determined through HPLC–MS/MS. Additionally, twenty-four Apcmin/+ mice were randomly assigned to normal diet (ND), high-fat diet (HFD), and SBJDD groups. The pharmacological effects and mechanism of SBJDD on colorectal adenoma carcinogenesis were assessed using RT-qPCR, HE staining, IHC staining, Western blot, IF staining, and Flow cytometry assays.ResultsOur clinical study has shown that SBJDD can regulate the gut microbiota composition and enhance SCFAs production in patients with colorectal adenoma. SBJDD alleviated colorectal adenoma formation and carcinogenesis, as well as protected the integrity of the intestinal barrier in the Apcmin/+ mice model compared to the HFD group. Additionally, SBJDD was found to regulate gut microbiota capable of producing SCFAs. G protein-coupled receptors GPR43, GPR41, and GPR109a were effectively activated in the SBJDD group, while HDAC1 and HDAC3 were inhibited. Furthermore, decreased expression levels of interleukin 1 beta (IL-1β) and interleukin 6 (IL-6), along with elevated expression level of interleukin 10 (IL-10), were observed in the colorectal tissue of the SBJDD group. Finally, SBJDD exhibited the ability to reduce the proportion of M1-type macrophages while increasing the proportion of M2-type macrophages.ConclusionsOur study objectively demonstrated the pharmacological effects of SBJDD in inhibiting the progression of colorectal adenoma and investigated its mechanisms in terms of regulating gut microbiota, increasing SCFAs, and reducing colorectal inflammation.

From complexity to clarity: development of CHM-FIEFP for predicting effective components in Chinese herbal formulas by using big data.

The presence of complex components in Chinese herbal medicine (CHM) hinders identification of the primary active substances and understanding of pharmacological principles. This study was aimed at developing a big-data-based, knowledge-driven in silico algorithm for predicting central components in complex CHM formulas. Network pharmacology (TCMSP) and clinical (GEO) databases were searched to retrieve gene targets corresponding to the formula ingredients, herbal components, and specific disease being treated. Intersections were determined to obtain disease-specific core targets, which underwent further GO and KEGG enrichment analyses to generate non-redundant biological processes and molecular targets for the formula and each component. The ratios of the numbers of biological and molecular events associated with a component were calculated with a formula, and entropy weighting was performed to obtain a fitting score to facilitate ranking and improve identification of the key components. The established method was tested on the traditional CHM formula Danggui Sini Decoction (DSD) for gastric cancer. Finally, the effects of the predicted critical component were experimentally validated in gastric cancer cells. An algorithm called Chinese Herb Medicine-Formula vs. Ingredients Efficacy Fitting & Prediction (CHM-FIEFP) was developed. Ferulic acid was identified as having the highest fitting score among all tested DSD components. The pharmacological effects of ferulic acid alone were similar to those of DSD. CHM-FIEFP is a promising in silico method for identifying pharmacological components of CHM formulas with activity against specific diseases. This approach may also be practical for solving other similarly complex problems. The algorithm is available at http://chm-fiefp.net/.

Pharmacognostic standardization and phytochemical evaluation of Ficus rumphii blume leaves in Thailand

BackgroundFicus rumphii Blume has long been used in ethnomedicinal practices and is regarded as one of the medicinal plants in Thai traditional herbal formulas for diabetes treatment. At present, published data on pharmacognostic study of this plant for its identity, quality, and purity is still limited. ObjectiveThis study aimed to establish the pharmacognostic standardization parameters of Ficus rumphii leaves in Thailand. MethodsThe pharmacognostic study of F. rumphii leaves collected from 12 different sources throughout Thailand was conducted according to the methods described in WHO guidelines including macroscopic, microscopic, physicochemical parameters, phytochemical screening, and TLC fingerprint. ResultsMacroscopic and microscopic characteristics of F. rumphii leaves were reported in this study. Physicochemical parameters showed the value of loss on drying (6.87 ± 0.79 %), total ash (16.28 ± 5.76 %), acid insoluble ash (7.54 ± 4.53 %), water content (9.58 ± 2.49 %), water extractive matters (4.71 ± 1.75 %) and ethanol extractive matters (1.30 ± 0.52 %). Preliminary phytochemical screening of hexane, ethanol, and aqueous extracted revealed the presence of phenolic, flavonoid, diterpene, triterpene, steroid, saponin, and cardiac glycoside which were confirmed by TLC fingerprint profiles of ethanolic extract of this plant. ConclusionThis study is the first report on the pharmacognostic specification of F. rumphii leaves in Thailand, which could be used as a reference for quality control and the species identification of this plant material.

Monotonic simple shear characteristics of K0 highly over-consolidated and remolded Wenzhou clay

The over consolidated clay is widely distributed in the seabed. Monotonic simple shear tests on K 0 consolidated clays with an over consolidation ratio (OCR) of 1 ∼ 14 were conducted through a multidirectional cyclic simple shear apparatus. The stress–strain relationship, pore pressure evolution, and shear strength variation under different OCRs were revealed, and differences between over and normally consolidated clay were compared. When OCR is below 8, peak values of shear stress and negative excess pore pressure both increase linearly with increasing OCR. However, the peak values tend to stabilize when OCR is above 8. Correspondingly, the occurrences of peak values no longer delay linearly, and the failure line is also shifted towards stronger strengths. An exponential formula is purposed and validated on accordance with numerous experimental data to describe the aforementioned pattern more precisely compared with the traditional power formula. Therefore, shear strengths of over consolidated clays with various OCRs and consolidation pressures can be accurately predicted according to the exponential formula and the shear strength of a normally consolidated sample with a certain consolidation pressure.