WAV E3 ubiquitin ligases mediate degradation of IAA32/34 in the TMK1-mediated auxin signaling pathway during apical hook development.

Auxin regulates plant growth and development through downstream signaling pathways, including the best-known SCFTIR1/AFB-Aux/IAA-ARF pathway and several other less characterized "noncanonical" pathways. Recently, one SCFTIR1/AFB-independent noncanonical pathway, mediated by Transmembrane Kinase 1 (TMK1), was discovered through the analyses of its functions in Arabidopsis apical hook development. Asymmetric accumulation of auxin on the concave side of the apical hook triggers DAR1-catalyzed release of the C-terminal of TMK1, which migrates into the nucleus, where it phosphorylates and stabilizes IAA32/34 to inhibit cell elongation, which is essential for full apical hook formation. However, the molecular factors mediating IAA32/34 degradation have not been identified. Here, we show that proteins in the CYTOKININ INDUCED ROOT WAVING 1 (CKRW1)/WAVY GROWTH 3 (WAV3) subfamily act as E3 ubiquitin ligases to target IAA32/34 for ubiquitination and degradation, which is inhibited by TMK1c-mediated phosphorylation. This antagonistic interaction between TMK1c and CKRW1/WAV3 subfamily E3 ubiquitin ligases regulates IAA32/34 levels to control differential cell elongation along opposite sides of the apical hook.

Crossmodal to unimodal transfer of temporal perceptual learning.

Subsecond temporal processing is crucial for activities requiring precise timing. Here, we investigated perceptual learning of crossmodal (auditory-visual or visual-auditory) temporal interval discrimination (TID) and its impacts on unimodal (visual or auditory) TID performance. The research purpose was to test whether learning is based on a more abstract and conceptual representation of subsecond time, which would predict crossmodal to unimodal learning transfer. The experiments revealed that learning to discriminate a 200-ms crossmodal temporal interval, defined by a pair of visual and auditory stimuli, significantly reduced crossmodal TID thresholds. Moreover, the crossmodal TID training also minimized unimodal TID thresholds with a pair of visual or auditory stimuli at the same interval, even if crossmodal TID thresholds are multiple times higher than unimodal TID thresholds. Subsequent training on unimodal TID failed to reduce unimodal TID thresholds further. These results indicate that learning of high-threshold crossmodal TID tasks can benefit low-threshold unimodal temporal processing, which may be achieved through training-induced improvement of a conceptual representation of subsecond time in the brain.

Swertia L.: A comprehensive review of its genetic relationship, chemical compositions, pharmacological effects, toxicities, and applications.

Swertia L., as a commonly used ethnic medicine, is widely distributed in Sichuan, Yunnan, and Xizang in China. Moreover, the medicinal plants of Swertia L. have been widely used and constitute one of the most important sources of various traditional medicines in China due to their prominent activities. In this review, the information on the classification, distribution, genetic relationship, chemical composition, pharmacological effects, toxicities, and applications of the medicinal plants in Swertia L. was summarized based on the scientific literature. The results indicated that the medicinal plants of Swertia L. mainly contained chemical components including triterpenes, xanthones, and iridoids. These compounds exert pharmacological effects including ameliorating diseases related to the liver and gallbladder. They also exert antiviral and antibacterial effects and can alleviate the increase in blood glucose levels. Especially, prescriptions related to Swertia L. have been widely adopted in preclinical and clinical studies to protect against diseases affecting the liver and the gallbladder, including hepatitis, cirrhosis, and cholecystitis. In addition, it also discusses toxicity studies and future perspectives and provides a reference for their clinical development and utilization.

Long-circulating doxorubicin and Schizandrin A liposome with drug-resistant liver cancer activity: in vitro and in vivo evaluation.

Co-loading doxorubicin (DOX) and Schizandrin A (SchA) long-circulating liposome (SchA-DOX-Lip) have been confirmed to have good antitumor activity in vitro. However, in vivo pharmacodynamics, targeting, safety, and mechanism of action of SchA-DOX-Lip still need to be further verified. We investigated the tumor inhibition effect, targeting, safety evaluation, and regulation of tumor apoptosis-related proteins of the SchA-DOX-Lip. MTT assay was used to investigate the inhibitory effect of SchA-DOX-Lip on CBRH7919 cells. The drug uptake of CBRH7919 cells was observed by inverted fluorescence microscope. The tumor-bearing nude mice models of CBRH7919 were established, and the anti-tumor effect of SchA-DOX-Lip in vivo was evaluated by tumor biological observation, H&E staining, and TUNEL staining. The distribution and targeting of SchA-DOX-Lip in nude mice models were investigated by small animal imaging and tissue distribution experiment of CBRH7919. The biosafety of SchA-DOX-Lip was evaluated by blood routine parameters, biochemical indexes, and H&E staining. The expression of tumor-associated apoptotic proteins (Bcl-2, Bax, and Caspase-3) was detected by immunohistochemistry anvd western blotting. The results showed that SchA-DOX-Lip had cytotoxicity to CBRH7919 cells which effectively inhibited the proliferation of CBRH7919 cells, improved the uptake of drugs by CBRH7919 cells and the targeting effect of drugs on tumor site. H&E staining and biochemical detection results showed that SchA-DOX-Lip had high biosafety and did not cause serious damage to normal tissues. Western-blotting and TUNEL staining results showed that SchA-DOX-Lip could improve the regulatory effect of drugs on tumor apoptosis proteins. It was demonstrated that SchA-DOX-Lip had high safety and strong tumor inhibition effects, providing a new method for the clinical treatment of hepatocellular carcinoma (HCC).

[Comparative study of purgative pharmacological effects and mechanisms of Moringa oleifera leaves and Rhei Radix et Rhizoma].

Moringa oleifera leaves are known for their "Virechana"(purgative) effect in Ayurvedic medicine in India. This study compared the purgative effects and mechanisms of M. oleifera leaves with the reference Rhei Radix et Rhizoma to establish a foundation for the further application of M. oleifera leaves in traditional Chinese medicine(TCM). Using network pharmacology and molecular docking methods, this study identified the material basis, common targets, and signaling pathways through which Rhei Radix et Rhizoma and M. oleifera leaves exerted their purgative pharmacological effects. A low-fiber diet-induced constipation mouse model was established to measure fecal parameters and small intestinal propulsion rate, and histological changes in the colon were observed using HE staining. Relative expression levels of relevant genes and target proteins were assessed using RT-qPCR and immunohistochemistry, respectively. The results showed that mapping the targets of Rhei Radix et Rhizoma and M. oleifera leaves onto the biological process network of constipation revealed close proximity, indicating that they may exert their therapeutic effects on constipation through similar biological processes. Molecular docking results indicated that compounds such as sennoside C and isoquercitrin could target serine/threonine protein kinases(AKT1) and mitogen-activated protein kinase 3(MAPK3), thereby affecting MAPK and calcium signaling pathways to promote defecation. Animal experiments demonstrated that both M. oleifera leaves and Rhei Radix et Rhizoma increased the number of fecal pellets and water content in constipated mice, improved small intestine motility, colon mucosal thickness, and muscle layer thickness, upregulated the gene expression levels of AKT1 and MAPK3 in the colon, and downregulated the expression of AQP3 protein. These findings suggest that M. oleifera leaves and Rhei Radix et Rhizoma share similarities in their therapeutic efficacy and mechanisms for treating constipation. Using Rhei Radix et Rhizoma as a reference can provide a better understanding of the characteristics of the "Virechana"(purgative) effect of M. oleifera leaves in TCM.

Predict multi-type drug-drug interactions in cold start scenario.

BACKGROUND: Prediction of drug-drug interactions (DDIs) can reveal potential adverse pharmacological reactions between drugs in co-medication. Various methods have been proposed to address this issue. Most of them focus on the traditional link prediction between drugs, however, they ignore the cold-start scenario, which requires the prediction between known drugs having approved DDIs and new drugs having no DDI. Moreover, they're restricted to infer whether DDIs occur, but are not able to deduce diverse DDI types, which are important in clinics. RESULTS: In this paper, we propose a cold start prediction model for both single-type and multiple-type drug-drug interactions, referred to as CSMDDI. CSMDDI predict not only whether two drugs trigger pharmacological reactions but also what reaction types they induce in the cold start scenario. We implement several embedding methods in CSMDDI, including SVD, GAE, TransE, RESCAL and compare it with the state-of-the-art multi-type DDI prediction method DeepDDI and DDIMDL to verify the performance. The comparison shows that CSMDDI achieves a good performance of DDI prediction in the case of both the occurrence prediction and the multi-type reaction prediction in cold start scenario. CONCLUSIONS: Our approach is able to predict not only conventional binary DDIs but also what reaction types they induce in the cold start scenario. More importantly, it learns a mapping function who can bridge the drugs attributes to their network embeddings to predict DDIs. The main contribution of CSMDDI contains the development of a generalized framework to predict the single-type and multi-type of DDIs in the cold start scenario, as well as the implementations of several embedding models for both single-type and multi-type of DDIs. The dataset and source code can be accessed at https://github.com/itsosy/csmddi .

Patchouli alcohol as a selective estrogen receptor ß agonist ameliorates AD-like pathology of APP/PS1 model mice.

Clinical evidence shows that postmenpausal women are almost twice as likely to develop Alzheimer's disease (AD) as men of the same age, and estrogen is closely related to the occurrence of AD. Estrogen receptor (ER) α is mainly expressed in the mammary gland and other reproductive organs like uterus while ERß is largely distributed in the hippocampus and cardiovascular system, suggesting that ERß selective agonist is a valuable drug against neurodegenerative diseases with low tendency in inducing cancers of breast and other reproductive organs. In this study we identified a natural product patchouli alcohol (PTA) as a selective ERß agonist which improved the cognitive defects in female APP/PS1 mice, and explore the underlying mechanisms. Six-month-old female APP/PS1 mice were administered PTA (20, 40 mg · kg-1 · d-1, i.g.) for 90 days. We first demonstrated that PTA bound to ERß with a dissociation constant (KD) of 288.9 ± 35.14 nM in microscale thermophoresis. Then we showed that PTA administration dose-dependently ameliorated cognitive defects evaluated in Morris water maze and Y-maze testes. Furthermore, PTA administration reduced amyloid plaque deposition in the hippocampus by promoting microglial phagocytosis; PTA administration improved synaptic integrity through enhancing BDNF/TrkB/CREB signaling, ameliorated oxidative stress by Catalase level, and regulated Bcl-2 family proteins in the hippocampus. The therapeutic effects of PTA were also observed in vitro: PTA (5, 10, 20 µM) dose-dependently increased phagocytosis of o-FAM-Aß42 in primary microglia and BV2 cells through enhancing ERß/TLR4 signaling; PTA treatment ameliorated o-Aß25-35-induced reduction of synapse-related proteins VAMP2 and PSD95 in primary neurons through enhancing ERß/BDNF/TrkB/CREB pathways; PTA treatment alleviated o-Aß25-35-induced oxidative stress in primary neurons through targeting ERß and increasing Catalase expression. Together, this study has addressed the efficacy of selective ERß agonist in the amelioration of AD and highlighted the potential of PTA as a drug lead compound against the disease.

FX5, a non-steroidal glucocorticoid receptor antagonist, ameliorates diabetic cognitive impairment in mice.

Diabetic cognitive impairment (DCI) is a common diabetic complication characterized by learning and memory deficits. In diabetic patients, hyperactivated hypothalamic-pituitary-adrenal (HPA) axis leads to abnormal increase of glucocorticoids (GCs), which causes the damage of hippocampal neurons and cognitive impairment. In this study we investigated the cognition-improving effects of a non-steroidal glucocorticoid receptor (GR) antagonist 5-chloro-N-[4-chloro-3-(trifluoromethyl) phenyl]thiophene-2-sulfonamide (FX5) in diabetic mice. Four weeks after T1DM or T2DM was induced, the mice were administered FX5 (20, 40 mg·kg-1·d-1, i.g.) for 8 weeks. Cognitive impairment was assessed in open field test, novel object recognition test, Y-maze test, and Morris water maze test. We showed that FX5 administration significantly ameliorated the cognitive impairments in both type 1 and 2 diabetic mice. Similar cognitive improvement was observed in diabetic mice following brain GR-specific knockdown by injecting AAV-si-GR. Moreover, AAV-si-GR injection occluded the cognition-improving effects of FX5, suggesting that FX5 functioning as a non-steroidal GR antagonist. In PA-treated primary neurons (as DCI model in vitro), we demonstrated that FX5 (2, 5, 10 µM) dose-dependently ameliorated synaptic impairment via upregulating GR/BDNF/TrkB/CREB pathway, protected against neuronal apoptosis through repressing GR/PI3K/AKT/GSK3ß-mediated tauopathy and subsequent endoplasmic reticulum stress. In LPS-treated primary microglia, FX5 dose-dependently inhibited inflammation through GR/NF-κB/NLRP3/ASC/Caspase-1 pathway. These beneficial effects were also observed in the hippocampus of diabetic mice following FX5 administration. Collectively, we have elucidated the mechanisms underlying the beneficial effects of non-steroidal GR antagonist FX5 on DCI and highlighted the potential of FX5 in the treatment of the disease.

Isobavachalcone: A comprehensive review of its plant sources, pharmacokinetics, toxicity, pharmacological activities and related molecular mechanisms.

Isobavachalcone (IBC), also known as isobapsoralcone, is a natural flavonoid widely derived from many medicinal plants, including Fabaceae, Moraceae, and so forth. IBC has been paid more and more attention by researchers in recent years due to its pharmacological activity in many diseases. This review aims to describe in detail the plant sources, pharmacokinetics, toxicity, pharmacological activities, and molecular mechanisms of IBC on various diseases. We found that IBC can be obtained not only by extraction but also by chemical synthesis. Pharmacokinetic studies have shown that IBC has low bioavailability, but can penetrate the blood-brain barrier and is widely distributed in the brain. Its pharmacological activities mainly include anticancer, antibacterial, anti-inflammatory, antiviral, neuroprotective, bone protection, and other activities. In particular, IBC shows strong anti-tumor and anti-inflammatory therapeutic potential due to its anti-cancer and anti-inflammatory activities. However, due to its hepatotoxicity, there may be more drug interactions. Therefore, more and more in-depth studies are needed for its clinical application. Mechanically, IBC can induce the production of reactive oxygen species (ROS), inhibit AKT, ERK, and Wnt pathways, and promote apoptosis of cancer cells through mitochondrial or endoplasmic reticulum pathways. IBC can inhibit the NF-κB pathway and the production of multiple inflammatory mediators by activating NRF2/HO-1 pathway, thus producing anti-inflammatory effects. Moreover, we discussed the limitations of current research on IBC and put forward some new perspectives and challenges, which provide a strong basis for clinical application and new drug development of IBC in the future.

Strong Optical Dipole Force Exerted on Molecules Having Low Rotational Temperature.

The optical dipole force acting on molecules is enhanced by decreasing the rotational temperature of the molecule and aligning the molecular axis with a linearly polarized nonresonant laser beam. The rotational temperature is decreased by increasing the source pressure from 2 to 81 bar. By using the effective polarizability directly pertaining to the optical dipole force, the force and the resulting change in the velocity of the molecules can be evaluated. Theoretical calculations are compared with measurements based on velocity map imaging techniques. If the rotational temperature is reduced from 295 to 1 K, the maximum alignment is increased from =0.33 to 0.92, and the average optical force is enhanced by 74 %.

Phase I/II study of adjuvant immunotherapy with sentinel lymph node T lymphocytes in patients with colorectal cancer.

Although the development of multi-disciplinary management has improved the survival of colorectal cancer (CRC), the prognosis of metastatic CRC patients remains poor. Accumulating evidence has demonstrated that immunotherapy with cancer vaccines and adoptive T cell transfusions may improve outcomes as an adjuvant to current standard CRC treatment. In this phase I/II study, 71 CRC patients who underwent radical surgery (stage I-III, n = 46) or palliative surgery (stage IV with non-resectable synchronous metastases, n = 25) were included. In the first part of this study, sentinel lymph nodes (SLNs) were intraoperatively identified in 55 patients (46 with stage I-III CRC and 9 with stage IV CRC). SLN-T lymphocytes were expanded ex vivo for a median of 28.5 days (range 23-33 days). Thereafter, a median of 153 × 10(6) cells (range 20.7-639.0 × 10(6)) were transfused. No treatment-related toxicity was observed. In the second part of this study, the stage IV patients were routinely followed. The 24-month survival rate of the SLN-T lymphocyte group was significantly higher than that of the control group: 55.6 versus 17.5% (p = 0.02). The median overall survival of the SLN-T lymphocyte and control groups was 28 and 14 months, respectively. Our study showed that adjuvant SLN-T lymphocyte immunotherapy is feasible and safe for postoperative CRC patients. Additionally, this therapy may improve the long-term survival of metastatic CRC. Further investigation of the clinical efficacy and anti-tumor immunity is warranted.

Rotational-State-Dependent Dispersion of Molecules by Pulsed Optical Standing Waves.

We report on the rotational-state-dependent, transverse acceleration of CS_{2} molecules affected by pulsed optical standing waves. The steep gradient of the standing wave potential imparts far stronger dipole forces on the molecules than propagating pulses do. Moreover, large changes in the transverse velocities (i.e., up to 80 m/s) obtained with the standing waves are well reproduced in numerical simulations using the effective polarizability that depends on the molecular rotational states. Our analysis based on the rotational-state-dependent effective polarizability can therefore serve as a basis for developing a new technique of state selection for both polar and nonpolar molecules.

[Effects on vascular permeability with different fluid resuscitation regimens during burn stage in swines].

OBJECTIVE: To explore the effects of different fluid resuscitation regimens on vascular permeability during burn stage in swines. METHODS: A total of 24 Guangxi-BAMA miniature swines were numbered from 1 to 24 and randomly divided by EXCEL 2007 into 4 groups of succinylated gelatin, hydroxyethyl starch (HES 130/0.4), Parkland (lactated Ringer's solution) and allogeneic plasma (n = 6 each). The model of severe burn shock was established. And fluid resuscitation therapy was applied according to the established regimens of burn shock fluid resuscitation. The parameters of heart rate, blood pressure, urine volume, central venous pressure (CVP) and pulmonary capillary wedge pressure (PCWP) were recorded. Blood samples were collected prior to burns and at intervals of 4, 8, 24 and 48 h post-burns. The plasma colloidal osmotic pressure was measured. Evens blue was intravenously injected at 30 min before sacrificing. Then lung tissue samples were obtained and pulmonary vascular permeability index (PMPI) was measured. Statistical analyses were performed. RESULTS: All swines survived shock stage. The inter-group comparison revealed no statistical difference in heart rate, blood pressure, urine volume, CVP or PCWP. The plasma colloidal osmotic pressures (mmHg, 1 mmHg = 0.133 kPa) of four groups at each interval were as follows: (1) pre-burn: 25.4 ± 1.0, 25.9 ± 0.9, 25.5 ± 1.1, 25.0 ± 1.0; (2) 4 h: 24.3 ± 1.0, 25.6 ± 0.9, 13.2 ± 0.5, 25.0 ± 1.1; (3) 8 h: 23.3 ± 0.8, 25.2 ± 1.2, 12.7 ± 0.5, 24.0 ± 0.9; (4) 24 h: 22.0 ± 0.8, 23.1 ± 1.0, 12.4 ± 0.4, 23.3 ± 0.8; (5) 48 h: 22.3 ± 0.8, 24.1 ± 0.8, 18.1 ± 0.4, 23.5 ± 0.9. No statistically significant differences existed at the intervals of pre-burn between four groups (all P > 0.05). The HES 130/0.4 group at 8 h was significantly higher than that of allogeneic plasma group at the same interval (P < 0.05). The Parkland group at 4, 8, 24, 48 h were significantly lower than those of allogeneic plasma group (all P < 0.05). The succinylated gelatin group at 8, 24, 48 h, the HES 130/0.4 group at 8, 24, 48 h, the Parkland group at 4, 8, 24, 48 h and allogeneic plasma at 8, 24, 48 h decreased versus those at pre-burns (all P < 0.05). No statistically significant differences existed in pulmonary vascular permeability between the groups of succinylated gelatin (7.6 ± 0.9) µg/g, HES 130/0.4 (7.9 ± 1.8) µg/g, and allogeneic plasma (7.6 ± 1.2) µg/g, but all lower than the Parkland group (26.1 ± 2.3) µg/g (all P < 0.05). CONCLUSIONS: Natural colloid or artificial colloid (HES 130/0.4 or succinylated gelatin) have similar effects on vascular permeability in swines with severe burns during shock stage. Both are superior to the Parkland group.

The inhibitory role of miR-214 in cervical cancer cells through directly targeting mitochondrial transcription factor A (TFAM).

Mitochondrial transcription factor A (TFAM) is a high-mobility group (HMG) protein and acts as a key regulator in mitochondrial DNA (mtDNA) replication, transcription, and inheritance. Accumulating evidence has demonstrated that TFAM plays an important role in tumorigenesis; however, the regulatory mechanism of TFAM in cervical cancer has not been revealed. In the current study, the au- thors found that with malignancy of cervical cancer, the protein expression of TFAM was gradually increased, while the expression of miRNA-214 was gradually downregulated. They further identified that TFAM is a target of miR-214. Forced overexpression of miRNA-214 significantly suppressed cell proliferation, cell cycle progression, colony-formation, and migration of cervical cancer Hela and Caski cells; however, upregulation of TFAM notably promoted cell proliferation, cell cycle progression, colony-formation, and migration of Hela and Caski cells. The authors further showed that miR-214 enhanced the susceptibility of Hela and Caski cells to the chemotherapy drug cisplatin. In conclusion, the current study provides a new sight for the regulatory pattern of miRNA-214 and TFAM in cervical cancer in vitro, indicating that miRNA-214 and MTFA may become important candidates for developing promising therapeutic strategies for the treatment of cervical cancer.

[Effects on ischemia-reperfusion injury with different fluid resuscitation regimens during burn shock stage in swines].

OBJECTIVE: To explore the effects on ischemia-reperfusion injury with different regimens of fluid resuscitation during severe burn shock stage in swines. METHODS: A total of 24 Guangxi BA-MA mini-swine were numbered from 1 to 24 and randomly divided by EXCEL 2007 into 4 groups of succinylated gelatin, hydroxyethyl starch (HES 130/0.4), Parkland and allogeneic plasma (n = 6 each). Then the burn shock model was established. And fluid resuscitation therapy was applied according to the established regimens of burn shock fluid resuscitation. Blood samples were collected from the animals prior to burn injury and again at intervals of 4, 8, 24 and 48 hours post-injury. The levels of malondialdehyde, superoxide dismutase (SOD), xanthine oxidase (XOD) and total antioxidant capacity (T-AOC) were measured. And the results were analyzed statistically. RESULTS: Six swines within each group survived the shock stage and the outliers in detection index were eliminated. Then there were 5 swines in each group. The MDA of allogeneic plasma group at intervals of 8 hours was significantly lower than that of succinylated gelatin group, but higher than that of Parkland group [(3.46 ± 0.40) vs (4.55 ± 0.82), (2.59 ± 0.35) µmol/L, both P < 0.05]. The level of SOD had statistical difference at 48 hours between the HES 130/0.4 and allogeneic plasma groups ((72.55 ± 5.70) vs (65.42 ± 5.07) U/ml, P < 0.05). The level of XOD of the succinylated gelatin group at 4, 8 hour and they increased when compared to pre-burn ((12.00 ± 0.57), (11.28 ± 0.71) vs (9.12 ± 0.51) U/L, both P < 0.01).Statistical significance was observed at 4, 8 hours between succinylated gelatin and allogeneic plasma groups ((10.39 ± 1.24), (9.59 ± 1.17) U/L, both P < 0.01). The T-AOC of HES 130/0.4 group at 8 hours exceed the pre-burn ((2.06 ± 0.43) vs (1.30 ± 0.35) U/ml, P < 0.05). The allogeneic plasma group at 4, 8 hours showed increase when compared to pre-burn ((1.55 ± 0.37), (2.59 ± 0.60) vs (1.06 ± 0.13) U/ml, both P < 0.05). The succinylated gelatin group at 8, 48 hours decreased during the corresponding phase of allogeneic plasma group ((1.14 ± 0.26), (0.89 ± 0.20) vs (2.59 ± 0.60), (1.16 ± 0.20) U/ml, both P < 0.05). The comparison at 24, 48 hours between HES 130/0.4 and allogeneic plasma groups ((1.84 ± 0.41), (1.53 ± 0.21) vs (1.13 ± 0.35), (1.16 ± 0.20) U/ml) had statistical difference (both P < 0.01). The Parkland group at intervals of 8 hours was lower than that of allogeneic plasma group ((1.31 ± 0.19) vs (2.59 ± 0.60) U/ml, P < 0.01). CONCLUSION: HES130/0.4 and allogeneic plasma have comparable the parallel minimum damage effect on ischemia-reperfusion injury during burn shock stage are.

Effects of ketogenic diet on weight loss parameters among obese or overweight patients with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trails.

Aim: To evaluate how effective a low carbohydrate ketogenic diet (KD) is for changing key physical measurements such as weight, waist circumference (WC), body mass index (BMI), and fat mass (FM) in women with polycystic ovary syndrome (PCOS) who were obese or overweight. Methods: Several online databases, including PubMed, Scopus, EMBASE, Cochrane Library, and Web of Science (WOS), were searched systematically to find relevant randomized controlled trials (RCTs) up until June 2023. The Q-test and I2 statistics were used to assess the level of heterogeneity among the included studies. The data were then combined using either a fixed or random effects model and presented as a weighted mean difference (WMD) along with a 95% confidence interval (CI). Results: Of the 682 citations, 11 RCTs were included. The pooled results showed a significant decrease in the WMD of weight levels [WMD = -9.13 kg; 95% CI, -11.88, -6.39, P < 0.001; I2 = 87.23%] following KD. Moreover, KD significantly reduced BMI levels [WMD = -2.93 kg/m2; 95% CI, -3.65, -2.21, P < 0.001; I2 = 78.81%] compared to the controls. Patients with PCOS received KD demonstrated significant decrease in WC [WMD = -7.62 cm; 95% CI, -10.73, -4.50, P < 0.001; I2 = 89.17%] and FM [WMD = -5.32 kg; 95% CI, -7.29, -3.36, P < 0.001; I2 = 83.97%]. Conclusion: KD was associated with lower weight loss (WL) parameters, including weight, BMI, WC, and FM, in obese or overweight women with PCOS, highlighting the significance of physicians and nurses in taking care of the nutritional needs of overweight/obese patients with PCOS.

Investigating the anti-lung cancer properties of Zhuang medicine Cycas revoluta Thunb. leaves targeting ion channels and transporters through a comprehensive strategy.

BACKGROUND: Cycas revoluta Thunb., known for its ornamental, economic, and medicinal value, has leaves often discarded as waste. However, in ethnic regions of China, the leaves (CRL) are used in folk medicine for anti-tumor properties, particularly for regulating pathways related to cancer. Recent studies on ion channels and transporters (ICTs) highlight their therapeutic potential against cancer, making it vital to identify CRL's active constituents targeting ICTs in lung cancer. PURPOSE: This study aims to uncover bioactive substances in CRL and their mechanisms in regulating ICTs for lung cancer treatment using network pharmacology, bioinformatics, molecular docking, molecular dynamics (MD) simulations, in vitro cell assays and HPLC. METHODS: We analyzed 62 CRL compounds, predicted targets using PubChem and SwissTargetPrediction, identified lung cancer and ICT targets via GeneCards, and visualized overlaps with R software. Interaction networks were constructed using Cytoscape and STRING. Gene expression, GO, and KEGG analyses were performed using R software. TCGA data provided insights into differential, correlation, survival, and immune analyses. Key interactions were validated through molecular docking and MD simulations. Main biflavonoids were quantified using HPLC, and in vitro cell viability assays were conducted for key biflavonoids. RESULTS: Venn diagram analysis identified 52 intersecting targets and ten active CRL compounds. The PPI network highlighted seven key targets. GO and KEGG analysis showed CRL-targeted ICTs involved in synaptic transmission, GABAergic synapse, and proteoglycans in cancer. Differential expression and correlation analysis revealed significant differences in five core targets in lung cancer tissues. Survival analysis linked EGFR and GABRG2 with overall survival, and immune infiltration analysis associated the core targets with most immune cell types. Molecular docking indicated strong binding of CRL ingredients to core targets. HPLC revealed amentoflavone as the most abundant biflavonoid, followed by hinokiflavone, sciadopitysin, and podocarpusflavone A. MD simulations showed that podocarpusflavone A and amentoflavone had better binding stability with GABRG2, and the cell viability assay also proved that they had better anti-lung cancer potential. CONCLUSIONS: This study identified potential active components, targets, and pathways of CRL-targeted ICTs for lung cancer treatment, suggesting CRL's utility in drug development and its potential beyond industrial waste.

Cycads: A comprehensive review of its botany, traditional uses, phytochemistry, pharmacology and toxicology.

Cycads, which primarily consist of the families Cycadaceae and Zamiaceae, possess intrinsic therapeutic attributes that are prominently expressed across their morphological spectrum, including roots, leaves, flowers, and seeds. In Chinese traditional medicine, the leaves of cycads are particularly revered for their profound healing capabilities. This meticulous review engages with existing literature on cycads and presents insightful avenues for future research. Over 210 phytoconstituents have been isolated and identified from various cycad tissues, including flavonoids, azoxy metabolites, sterols, lignans, non-proteogenic amino acids, terpenoids, and other organic constituents. The contemporary pharmacological discourse highlights the antineoplastic, antimicrobial, and antidiabetic activities inherent in these ancient plants, which are of particular importance to the field of oncology. Despite the prevalent focus on crude extracts and total flavonoid content, our understanding of the nuanced pharmacodynamics of cycads lags considerably behind. The notoriety of cycads derived toxicity, notably within the context of Guam's neurological disease cluster, has precipitated an established emphasis on toxicological research within this field. As such, this critical review emphasizes nascent domains deserving of academic and clinical pursuit, whilst nested within the broader matrix of current scientific understanding. The systematic taxonomy, traditional applications, phytochemical composition, therapeutic potential, and safety profile of cycads are holistically interrogated, assimilating an indispensable repository for future scholarly inquiries. In conclusion, cycads stand as a veritable treasure trove of pharmacological virtue, displaying remarkable therapeutic prowess and holding vast promise for ongoing scientific discovery and clinical utilization.