Targeting bone homeostasis regulation: potential of traditional Chinese medicine flavonoids in the treatment of osteoporosis.

Osteoporosis is a systemic metabolic disease characterized by disrupted bone formation/resorption and homeostasis. Flavonoids extracted from traditional Chinese medicinal plants regulate bone homeostasis by intervening in differentiating bone marrow mesenchymal stem cells, balancing the bone immune system, inhibiting oxidative stress response, and reversing iron overload. The target molecules and signaling pathways, such as Wnt/ß-catenin and OPG/RANKL/RANK, directly affect osteoblast/osteoclast activity, exhibiting significant potential in the treatment of OP. Therefore, this study presents a systematic review of the recent literature to provide comprehensive information on the traditional Chinese medicine flavonoids involved in the regulation of bone homeostasis. Also, the molecular mechanisms and pharmacological uses of these metabolites are summarized, and their clinical translation and development potential are discussed.

Synergistic amelioration between Ligusticum striatum DC and borneol against cerebral ischemia by promoting astrocytes-mediated neurogenesis.

ETHNOPHARMACOLOGICAL RELEVANCE: Ligusticum chuanxiong Hort (LCH), with the accepted name of Ligusticum striatum DC in "The Plant List" database, is a widely used ethnomedicine in treating ischemic stroke, and borneol (BO) is usually prescribed with LCH for better therapy. Our previous study confirmed their synergistic effect on neurogenesis against cerebral ischemia. However, the underlying mechanism is still unclear. AIM OF THE STUDY: More and more evidence indicated that astrocytes (ACs) might be involved in the modulation of neurogenesis via polarization reaction. The study was designed to explore the synergic mechanism between LCH and BO in promoting astrocyte-mediated neurogenesis. MATERIALS AND METHODS: After primary cultures and identifications of ACs and neural stem cells (NSCs), the oxygen-glucose deprivation (OGD) model and the concentrations of LCH and BO were optimized. After the OGD-injured ACs were treated by LCH, BO, and their combination, the conditioned mediums were used to culture the OGD-injured NSCs. The proliferation, migration, and differentiation of NSCs were assessed, and the secretions of BDNF, CNTF, and VEGF from ACs were measured. Then the expressions of C3 and PTX3 were detected. Moreover, the mice were performed a global cerebral ischemia/reperfusion model and treated with LCH and (or) BO. After the assessments of Nissl staining, the expressions of Nestin, DCX, GFAP, C3, PTX3, p65 and p-p65 were probed. RESULTS: The most appropriate duration of OGD for the injury of both NSCs and ACs was 6 h, and the optimized concentrations of LCH and BO were 1.30 µg/mL and 0.03 µg/mL, respectively. The moderate OGD environment induced NSCs proliferation, migration, astrogenesis, and neurogenesis, increased the secretions of CNTF and VEGF from ACs, and upregulated the expressions of C3 and PTX3. For the ACs, LCH further increased the secretions of BDNF and CNTF, enhanced PTX3 expression, and reduced C3 expression. Additionally, the conditioned medium from LCH-treated ACs further enhanced NSC proliferation, migration, and neurogenesis. The in vivo study showed that LCH markedly enhanced the Nissl score and neurogenesis, and decreased astrogenesis which was accompanied by downregulations of C3, p-p65, and p-p65/p65 and upregulation of PTX3. BO not only decreased the expression of C3 in ACs both in vitro and in vivo but also downregulated p-p65 and p-p65/p65 in vivo. Additionally, BO promoted the therapeutic effect of LCH for most indices. CONCLUSION: A certain degree of OGD might induce ACs to stimulate the proliferation, astrogenesis, and neurogenesis of NSCs. LCH and BO exhibited a marked synergy in promoting ACs-mediated neurogenesis and reducing astrogenesis, in which LCH played a dominant role and BO boosted the effect of LCH. The mechanism of LCH might be involved in switching the polarization of ACs from A1 to A2, while BO preferred to inhibit the formation of A1 phenotype via downregulating NF-κB pathway.

The effect of mindfulness-based interventions on mental health outcomes and wellbeing of informal caregivers of people with mental illness: A systematic review and meta-analysis.

The increasing prevalence of mental illness has resulted in a growing burden on informal caregivers. Mindfulness-based interventions, as a form of psychotherapy, have shown efficacy in alleviating psychological stress and enhancing emotional and physical well-being. However, the utilisation of mindfulness-based interventions for informal caregivers of individuals with mental illness remains limited. The aim of the meta-analysis is to evaluate the impact of mindfulness-based interventions on the mental health and well-being among informal caregivers of people with mental illness. A comprehensive literature search was conducted across seven electronic databases (PubMed, Scopus, Web of Science, Cochrane Library, Embase, APA PsycINFO and CINAHL Ultimate) from the inception of these databases until 20 July 2023. Two authors independently screened the studies and extracted the relevant data. The meta-analysis was performed by using Stata 12.0 software, and the effect sizes were calculated utilising standardised mean difference (SMD) along with their corresponding 95% confidence intervals (CI). The meta-analysis included 13 studies with 1007 participants, and the results demonstrated that mindfulness-based interventions were efficacious in reducing stress (SMD = -0.80, 95% CI [-1.33, -0.28], p = 0.003), depression (SMD = -0.43, 95% CI [-0.62, -0.24], p < 0.001) and caregiver burden (SMD = -0.21, 95% CI [-0.40, -0.01], p = 0.038), and enhancing the mindfulness level (SMD = 0.37, 95% CI [0.09, 0.65], P = 0.010) and quality of life (SMD = 0.22, 95% CI [0.04, 0.39], p = 0.015) among informal caregivers of people with mental illness, but not on anxiety reduction (SMD = -0.19, 95% CI [-0.49, 0.10], p = 0.198). Furthermore, future research should aim to employ more rigorous methodologies to confirm the effectiveness.

Recent advances in functionalized ferrite nanoparticles: From fundamentals to magnetic hyperthermia cancer therapy.

Cancers are fatal diseases that lead to most death of human beings, which urgently require effective treatments methods. Hyperthermia therapy employs magnetic nanoparticles (MNPs) as heating medium under external alternating magnetic field. Among various MNPs, ferrite nanoparticles (FNPs) have gained significant attention for hyperthermia therapy due to their exceptional magnetic properties, high stability, favorable biological compatibility, and low toxicity. The utilization of FNPs holds immense potential for enhancing the effectiveness of hyperthermia therapy. The main hurdle for hyperthermia treatment includes optimizing the heat generation capacity of FNPs and controlling the local temperature of tumor region. This review aims to comprehensively evaluate the magnetic hyperthermia treatment (MHT) of FNPs, which is accomplished by elucidating the underlying mechanism of heat generation and identifying influential factors. Based upon fundamental understanding of hyperthermia of FNPs, valuable insights will be provided for developing efficient nanoplatforms with enhanced accuracy and magnetothermal properties. Additionally, we will also survey current research focuses on modulating FNPs' properties, external conditions for MHT, novel technical methods, and recent clinical findings. Finally, current challenges in MHT with FNPs will be discussed while prospecting future directions.

Effects of mindfulness-based interventions on cardiovascular risk factors: An umbrella review of systematic reviews and meta-analyses.

OBJECTIVE: Reviews have shown that mindfulness-based interventions (MBIs) were effective in improving cardiovascular risk factors (CVRFs), but the results were contradictory. This umbrella review aimed to summarize and grade the existing reviews on CVRFs associated with MBIs. METHODS: The protocol of this umbrella review had been registered in PROSPERO (CRD42022356812). PubMed, Web of science, Embase, The Cochrane Library, Scopus, Medline, PsycINFO and CINAHL were searched from database inception to 20 July 2022. The quality of evidence was assessed through GRADE. RESULTS: Twenty-seven reviews with 14,923 participants were included. Overall, 45% of reviews had low heterogeneity (I2 < 25%). For the quality of evidence, 31% were rated very low, 42% were rated low, 17% were rated moderate and 10% were rated high. MBIs significantly improved systolic blood pressure [SMD -5.53 mmHg (95% CI -7.81, -3.25)], diastolic blood pressure [SMD -2.13 mmHg (95% CI -2.97, -1.30)], smoking [Cohen's d 0.42 (95% CI 0.20, 0.64)], glycosylated hemoglobin [MD 0.01 (95% CI -0.43, -0.07)], binge eating behavior [SMD -6.49 (95% CI -10.80, -2.18)], depression [SMD -0.72 (95% CI -1.23, -0.21)] and stress [SMD -0.67 (95% CI -1.00, -0.34)]. CONCLUSIONS: In conclusion, this umbrella review provided evidence for the role of MBIs in the improvement of CVRFs.

Arjunolic acid protects the intestinal epithelial barrier, ameliorating Crohn's disease-like colitis by restoring gut microbiota composition and inactivating TLR4 signalling.

BACKGROUND AND AIMS: Crohn's disease (CD) is characterized by an overabundance of epithelial cell death and an imbalance in microflora, both of which contribute to the dysfunction of the intestinal barrier. Arjunolic acid (AA) has anti-apoptotic effects and regulates microbiota efficacy. The objective of this study was to assess the impact of the treatment on colitis resembling Crohn's disease, along with exploring the potential underlying mechanism. METHODS: CD animal models were created using Il-10-/- mice, and the impact of AA on colitis in mice was evaluated through disease activity index, weight fluctuations, pathological examination, and assessment of intestinal barrier function. To clarify the direct role of AA on intestinal epithelial cell apoptosis, organoids were induced by LPS, and TUNEL staining was performed. To investigate the potential mechanisms of AA in protecting the intestinal barrier, various methods including bioinformatics analysis and FMT experiments were employed. RESULTS: The treatment for AA enhanced the condition of colitis and the function of the intestinal barrier in Il-10-/- mice. This was demonstrated by the amelioration of weight loss, reduction in tissue inflammation score, and improvement in intestinal permeability. Moreover, AA suppressed the apoptosis of intestinal epithelial cells in Il-10-/- mice and LPS-induced colon organoids, while also reducing the levels of Bax and C-caspase-3. In terms of mechanism, AA suppressed the activation of TLR4 signaling in Il-10-/- mice and colon organoids induced by LPS. In addition, AA increased the abundance of short-chain fatty acid-producing bacteria in the stool of Il-10-/- mice, and transplantation of feces from AA-treated mice improved CD-like colitis. CONCLUSIONS: The results of our study demonstrate that AA has a protective effect on the intestinal barrier in Crohn's disease-like colitis by preventing apoptosis. Additionally, this groundbreaking study reveals the capacity of AA to hinder TLR4 signaling and alter the makeup of the intestinal microbiome. The findings present fresh possibilities for treating individuals diagnosed with Crohn's disease. AA offers a hopeful novel strategy for managing Crohn's disease by obstructing crucial pathways implicated in intestinal inflammation and enhancing the gut microbiota.

Exploring the mechanism of traditional Chinese medicine in regulating gut-derived 5-HT for osteoporosis treatment.

Osteoporosis is a systemic bone disease characterized by an imbalance in the relationship between osteoblasts, osteocytes, and osteoclasts. This imbalance in bone metabolism results in the destruction of the bone's microstructure and an increase in bone brittleness, thereby increasing the risk of fractures. Osteoporosis has complex causes, one of which is related to the dysregulation of 5-hydroxytryptamine, a neurotransmitter closely associated with bone tissue metabolism. Dysregulation of 5-HT directly or indirectly promotes the occurrence and development of osteoporosis. This paper aims to discuss the regulation of 5-HT by Traditional Chinese Medicine and its impact on bone metabolism, as well as the underlying mechanism of action. The results of this study demonstrate that Traditional Chinese Medicine has the ability to regulate 5-HT, thereby modulating bone metabolism and improving bone loss. These findings provide valuable insights for future osteoporosis treatment.

Influence of geographical location and outdoor meteorological parameters on indoor humidity environment in rural residential buildings during the Plum Rains Season in the hot summer and cold winter region.

Plum Rains Season (PRS) has the typical characteristics of outdoor air temperature dramatic changes and high air humidity in the hot summer and cold winter region in China. When the outdoor temperature rises rapidly during PRS, the building envelope surface temperature is probably lower than the indoor air dew point temperature, resulting in moisture condensation. This paper evaluates the influence of geographical location and outdoor meteorological parameters on the indoor humidity environment. The effects of critical parameters such as altitude, average temperature, relative humidity, total precipitation, total precipitation days, atmospheric pressure, and wind speed on the building envelope moisture condensation in nine typical cities in the hot summer and cold winter region were simulated and analyzed. The results show that the Condensation Frequency (CFn) in the western, central, and eastern regions reached the highest in April, May, and June, respectively. Among the nine typical cities, Changsha has the highest Condensation Risk (CR). In addition, the altitude, total precipitation, and atmospheric pressure have little effect on the indoor humidity environment, and it is not directly related to CR; The average temperature and total precipitation days were not related to CR in the western and eastern regions and positively correlated with CR in the central region; The wind speed was positively correlated with CR in the western and central regions and negatively correlated in the eastern region; The relative humidity can affect the indoor humidity environment and moisture condensation on the inner surface of walls, when the relative humidity increases, the CR increases.

Maternal Folic Acid Supplementation Improves the Intestinal Health of Offspring Porcine by Promoting the Proliferation and Differentiation of Intestinal Stem Cells.

Maternal folic acid intake has important effects on offspring growth and development. The mechanism involved in the renewal of intestinal epithelial cells remains unclear. Thus, this study aimed to investigate the potential effect of maternal folic acid supplementation during gestation and lactation on the structural and functional development of the small intestine in piglet offspring. Twenty-four Duroc sows were assigned to a control group (CON) and a folic-acid-supplemented group (CON + FA, supplemented with 15 mg/kg of folic acid). The results showed that maternal folic acid supplementation throughout gestation and lactation significantly increased the body weight, serum folate level, and intestinal folate metabolism in piglets. It also improved the villus length, villus height-to-crypt depth ratio, and transcript levels of nutrient transporters (GLUT4, SNAT2, FABP2, and SLC7A5) in piglets' duodenum and jejunum. In addition, maternal folic acid supplementation increased Ki67-positive cells and the expression of proliferation-related marker genes (C-Myc, CyclinD1, and PCNA) in piglets' intestinal stem cells. It also boosted the expression of genes associated with mature secreted cells (ChrA, Muc2, Lyz, Vil1), indicating enhanced proliferation and differentiation of intestinal stem cells. These findings demonstrate that maternal folic acid supplementation enhances growth performance and gut health in piglet offspring by promoting epithelial cell renewal equilibrium.

Cucurbitacin C suppresses the progression of pancreatic ductal adenocarcinoma via inhibition of the cGMP-PKG-VASP axis.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most devastating diseases; it has a considerably poor prognosis and may become the second most lethal malignancy in the next 10 years. Chemotherapeutic resistance is common in PDAC; thus, it is necessary to exploit effective alternative drugs. In recent years, traditional folk medicines and their extracts have shown great potential in cancer treatment. The seed of Lagenaria siceraria (Molina) Standl. is a traditional medicine in Asia. Because of its analgesic effects and ability to reduce swelling, it is often used as an adjuvant treatment for abdominal tumors. Cucurbitacin compounds are extracts abundant in Lagenaria siceraria (Molina) Standl. Here, we found that cucurbitacin C (CuC), a member of the cucurbitacin family, has apparent anti-PDAC therapeutic properties. CuC decreased the viability and suppressed the proliferation of PDAC cells in a time- and dose-dependent manner. Further studies revealed that CuC inhibited cell migration and invasion by inhibiting epithelial-mesenchymal transition (EMT). In addition, G2/M arrest was induced, and the apoptotic pathway was activated. Transcriptomic and bioinformatic analyses showed that CuC inhibited the cGMP-PKG-VASP axis, increasing the content of cGMP to restore tumor characteristics. The antitumor activity of CuC in vivo was verified through animal experiments, and no obvious side effects were observed. Overall, our study indicates a candidate therapeutic compound for PDAC that is worthy of further development.

Targeting different phenotypes of macrophages: A potential strategy for natural products to treat inflammatory bone and joint diseases.

BACKGROUND: Macrophages, a key class of immune cells, have a dual role in inflammatory responses, switching between anti-inflammatory M2 and pro-inflammatory M1 subtypes depending on the specific environment. Greater numbers of M1 macrophages correlate with increased production of inflammatory chemicals, decreased osteogenic potential, and eventually bone and joint disorders. Therefore, reversing M1 macrophages polarization is advantageous for lowering inflammatory factors. To better treat inflammatory bone disorders in the future, it may be helpful to gain insight into the specific mechanisms and natural products that modulate macrophage polarization. OBJECTIVE: This review examines the impact of programmed cell death and different cells in the bone microenvironment on macrophage polarization, as well as the effects of natural products on the various phenotypes of macrophages, in order to suggest some possibilities for the treatment of inflammatory osteoarthritic disorders. METHODS: Using 'macrophage polarization,' 'M1 macrophage' 'M2 macrophage' 'osteoporosis,' 'osteonecrosis of femoral head,' 'osteolysis,' 'gouty arthritis,' 'collagen-induced arthritis,' 'freund's adjuvant-induced arthritis,' 'adjuvant arthritis,' and 'rheumatoid arthritis' as search terms, the relevant literature was searched using the PubMed, the Cochrane Library and Web of Science databases. RESULTS: Targeting macrophages through different signaling pathways has become a key mechanism for the treatment of inflammatory bone and joint diseases, including HIF-1α, NF-κB, AKT/mTOR, JAK1/2-STAT1, NF-κB, JNK, ERK, p-38α/ß, p38/MAPK, PI3K/AKT, AMPK, AMPK/Sirt1, STAT TLR4/NF-κB, TLR4/NLRP3, NAMPT pathway, as well as the programmed cell death autophagy, pyroptosis and ERS. CONCLUSION: As a result of a search of databases, we have summarized the available experimental and clinical evidence supporting herbal products as potential treatment agents for inflammatory osteoarthropathy. In this paper, we outline the various modulatory effects of natural substances targeting macrophages in various diseases, which may provide insight into drug options and directions for future clinical trials. In spite of this, more mechanistic studies on natural substances, as well as pharmacological, toxicological, and clinical studies are required.

Solitary fibrous tumor of the central nervous system invading and penetrating the skull: A case report.

Solitary fibrous tumor (SFT) of the central nervous system is a rare spindle cell tumor of mesenchymal origin. The present study reports the case of a 44-year-old male patient with SFT. Magnetic resonance imaging demonstrated that the majority of the intracranial tumors exhibited uneven low signals on T1-weighted imaging (T1WI) and low mixed signals on T2WI, and there was an enhancement on enhanced scanning. Furthermore, the distal part of the left occipital lobe exhibited hypersignals on T1WI and T2WI, and this was significantly enhanced following enhanced scanning. The lower part of the scalp exhibited low signals on T1WI and high signals on T2WI, and there was no notable enhancement following enhanced scanning. Magnetic resonance spectroscopy demonstrated an elevated choline/creatine peak in the solid part of the tumor. Under the microscope, the tumor exhibited characteristic 'staghorn-shaped' blood vessels. As SFT is difficult to differentially diagnose via imaging, immunohistochemical analysis of CD34, vimentin and signal transducer and activator of transcription 6 was performed for the definitive diagnosis of SFT. Of note, surgical resection was the preferred treatment for SFT; however, due to the rarity of the tumor, subsequent adjuvant therapy and prognosis require further investigation.

The effect of tomato and lycopene on clinical characteristics and molecular markers of UV-induced skin deterioration: A systematic review and meta-analysis of intervention trials.

Lycopene as a natural antioxidant that have been studied for ultraviolet radiation (UVR) photo protection and is one of the most effective carotenoids to scavenge reactive oxygen species (ROS). This review aims to summarize the protective effect of tomato and lycopene on skin photo damage and skin photoaging in healthy subjects by reviewing the existing population intervention experiments. A total of five electronic databases including PubMed, Scopus, EBSCO, Web of Science and Cochrane Library were searched from inceptions to January 2021 without any restriction. Out of 19336 publications identified, 21 fulfilled the inclusion criteria and were meta-analysis. Overall, interventions supplementing tomato and lycopene were associated with significant reductions in Δa*, MMP-1, ICAM-1 and skin pigmentation; while tomato and lycopene supplementation were associated with significant increase in MED, skin thickness and skin density. Based on the results of this systematic review and meta-analysis, supplementation with tomato and lycopene could reduce skin erythema formation and improve the appearance and pigmentation of the skin, thereby preventing light-induced skin photodamage and skin photoaging. Lycopene-rich products could be used as endogenous sun protection and may be a potential nutraceutical for sun protection.

Effects of fermented dairy products on inflammatory biomarkers: A meta-analysis.

AIM: Fermented dairy products (FDPs) are made from raw milk under the action of specific microorganisms by lactic acid bacteria fermentation or co-fermentation of lactic acid bacteria, bifidobacteria, and yeast. The aim of this study was to explore the effects of FDPs on inflammatory biomarkers. DATA SYNTHESIS: A comprehensive search was conducted on four electronic databases, including PubMed, Web of Science, Embase, and the Cochrane Library. Finally, fourteen trials (15 arms) were included in this meta-analysis: yogurt (n = 9), fermented milk (n = 4), and kefir (n = 2). Additionally, the random effects model or fixed-effects model was used to pool the study results. Firstly, the analysis indicated that FDPs' supplementation decreased the levels of C-reactive protein (CRP) (SMD = -0.21; 95% CI: -0.40, -0.02; P = 0.033) and increased interferon-gamma (IFN-γ) levels (SMD = 0.12; 95% CI: 0.01, 0.23; P = 0.033). Furthermore, we obtained some statistically significant results in the following subgroups: CRP decreased in participants with metabolic diseases. IFN-γ increased in the intervention that lasted ≥12 weeks, Asian, yogurt, and healthy population. Finally, there was no significant effect on tumor necrosis factor-alpha, interleukin (IL)-6, IL-10, and IL-2. CONCLUSIONS: FDPs reduced CRP and increased IFN-γ, but they had no effect on other inflammatory markers. The results showed that the consumption of FDPs was slightly associated with reduced inflammation, but because of the limited literature, these results should be interpreted with caution.

Exploring the synergic mechanism of Ligusticum striatum DC. and borneol in attenuating BMECs injury and maintaining tight junctions against cerebral ischaemia based on the HIF-1α/VEGF signalling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ligusticum striatum DC., also known as Ligusticum chuanxiong Hort. (LCH), is widely used in China for its excellent effect in ischaemic stroke (IS) patients, and borneol (BO) has been confirmed to maintain the blood‒brain barrier (BBB) after stroke. They are often used as a combination in the prescriptions of IS patients. Although the advantage of their combined treatment in improving brain ischaemia has been verified, their synergistic mechanism on BBB maintenance is still unclear. AIM OF THE STUDY: This study was designed to evaluate the synergistic effect of maintaining the BBB between LCH and BO against IS and to further explore the potential mechanism. MATERIALS AND METHODS: After primary mouse brain microvascular endothelial cells (BMECs) were extracted and identified, the duration of oxygen-glucose deprivation (OGD) and the doses of LCH and BO were optimized. Then, the cells were divided into five groups: control, model, LCH, BO, and LCH + BO. Cell viability, injury degree, proliferation and migration were detected by CCK-8, LDH, EdU and wound-healing assays, respectively. Hoechst 33342 staining was adopted to detect the apoptosis rate, and western blotting was employed to observe the expressions of Bax, Bcl-2, caspase-3 and cleaved caspase-3. The TEER value and NaF permeability were measured to assess tight junction (TJ) function, while ZO-1, occludin and claudin-5 were also probed by western blotting. Moreover, the HIF-1α/VEGF pathway was observed to explore the underlying mechanism of BBB maintenance. In vivo, global cerebral ischaemia/reperfusion (GCIR) surgery was performed to establish an IS model. After treatment with LCH (200 mg/kg) and/or BO (160 mg/kg), histopathological structure and BMECs repair were observed by HE staining and immunohistochemistry of vWF. Meanwhile, TJ-associated proteins in vivo were also detected by western blotting. RESULTS: Basically, LCH and BO had different emphases. LCH significantly attenuated the vacuolar structure, nuclear pyknosis and neuronal loss of GCIR mice, while BO focused on promoting BMECs proliferation and angiogenesis and inhibiting the degradation of TJ-associated proteins in vivo after IS. Interestingly, their combination further enhanced these effects. OGD injury markedly reduced the viability, proliferation and migration of primary BMECs; decreased the ratio of Bcl-2/Bax, TEER value, and the expressions of ZO-1, occludin and claudin-5; induced LDH release and apoptosis; and increased the cleaved caspase-3/caspase-3 ratio and NaF permeability. Meanwhile, BO might be the main contributor to the combinative treatment in ameliorating OGD-induced damage of BMECs and degradation of TJ-related proteins, and the potential mechanism might be involved in upregulating the HIF-1α/VEGF signalling pathway. Although LCH showed no obvious improvement, it could enhance the therapeutic effect of BO. Interestingly, their combination even produced some new improvements, including the reduction of cleaved caspase-3 and increase in TEER value, none of which were exhibited in their monotherapies. CONCLUSIONS: LCH and BO exhibited complementary therapeutic features in alleviating cerebral ischaemic injury by inhibiting BMECs apoptosis, maintaining the BBB and attenuating the loss of neurons. LCH preferred to protect ischaemic neurons, while BO played a key role in protecting BMECs, maintaining the BBB and TJs by activating the HIF-1α/VEGF signalling pathway.

Linderalactone Suppresses Pancreatic Cancer Development In Vitro and In Vivo via Negatively Regulating PI3K/AKT Signaling Pathway.

Linderalactone is one of the main extracts of Linderae Radix, which is widely used in traditional Chinese medicine. There have been few studies on the antitumor effect of linderalactone in the past. In this study, we explored the anti-pancreatic cancer activity of linderalactone in vitro and in vivo. The results showed that linderalactone inhibited the proliferation of pancreatic cancer cells in a time- and dose-dependent manner. Cell migration and invasion were significantly inhibited by linderalactone. The cell cycle was arrested in the G2/M phase, and the expression levels of cell cycle-associated proteins changed significantly with linderalactone treatment. In addition, linderalactone induced cell apoptosis and altered the expression of apoptotic markers, such as caspase 3 and PARP1. Mechanistically, linderalactone suppressed the PI3K/AKT signaling pathway by downregulating the phosphorylation of PI3K and AKT. The xenograft study results were consistent with the in vitro results, and there was no obvious chemical toxicity. Thus, our research demonstrated that linderalactone exhibits antitumor activity against pancreatic cancer and may be developed as a potential anti-pancreatic cancer agent in the future.

Huogu injection alleviates SONFH by regulating adipogenic differentiation of BMSCs via targeting the miR-34c-5p/MDM4 pathway.

Although the precise pathogenesis of steroid-induced osteonecrosis of femoral head (SONFH) is not yet fully understood, evidence shows miRNAs-mediated posttranscription control directs the adipogenesis of bone marrow mesenchymal stem cells (BMSCs) and plays a pivotal role in the SONFH processes. Huogu injection formulated according to traditional Chinese medicine (TCM) theory has been used to treat SONFH by intra-articular injection. In this study, we asked whether the therapeutic effects of Huogu injection might depend on the inhibition of adipogenic differentiation of BMSCs, and if so, the pathway might be a therapeutic target to promote bone repair. Consequently, miR-34c-5p was upregulated in the dexamethasone (DEX)-treated BMSCs and might participate in the adipogenesis of BMSCs. TargetScan database and the luciferase reporter assay showed miR-34c-5p targeted on the MDM4 and negatively regulated its expression. Huogu injection in vitro inhibited the adipogenesis in the DEX-treated BMSCs by inhibiting the expression levels of PPARγ and C/EBPα, as well as reducing miR-34c-5p to prevent the degradation of MDM4. Moreover, miR-34c-5p mimic or MDM4 knockdown using shRNA neutralized the anti-adipogenesis of Huogu injection in BMSCs. In vivo, the results of X-ray imaging confirmed that Huogu injection alleviated the bone loss in rat SONFH. Consistent with results in vitro, Huogu injection reduced the lipid accumulation, removed the suppression of MDM4 by downregulating the expression of miR-34c-5p, and inhibited the expression of C/EBPα and PPARγ in bone tissues. When the lentivirus encoding miR-34c-5p was conducted by intra-articular injection, the overexpression of miR-34c-5p antagonized the therapeutic effects of Huogu injection. Our results underline the critical importance of the miR-34c-5p/MDM4 pathway in regulating the adipogenic outcome of BMSCs, suggesting the miR-34c-5p as a potentially effective therapeutic target in SONFH. These results further reinforce the potential of Huogu injection as an alternative approach in SONFH.

Zingiberaceae plants/curcumin consumption and multiple health outcomes: An umbrella review of systematic reviews and meta-analyses of randomized controlled trials in humans.

This umbrella review is to recapitulate and grade the available evidence of associations between consumption of Zingiberaceae plants/curcumin (Cur) and multiple health-related outcomes. This study included 161 meta-analyses of randomized controlled trials in 76 articles with 67 unique health outcomes. Data on heterogeneity and publication bias are considered to assess the quality of evidence. Based on the different impact of Zingiberaceae plants/Cur on human health, the advantages outweigh the disadvantages. Zingiberaceae plants/Cur can mainly improve metabolic syndrome, non-alcoholic fatty liver disease, cardiovascular disease, and some chronic inflammatory diseases, likewise, obviously relief the pain of osteoarthritis and related diseases. Ginger supplements have been shown to improve vomiting during pregnancy and to relieve nausea and vomiting caused by chemotherapy and surgery. The surgery is any type of surgery, including laparoscopic surgery, gynecological surgery and mixed surgery. Beneficial associations were found with Cur intervention in gastrointestinal, neurological and oral diseases. Zingiberaceae plants/Cur are generally safe and favorable for multiple health outcomes in humans. High-quality research is further needed to prove the observed associations.

Metabolomic Profiling Reveals Protective Effects and Mechanisms of Sea Buckthorn Sterol against Carbon Tetrachloride-Induced Acute Liver Injury in Rats.

The present study was designed to examine the efficacy and protection mechanisms of sea buckthorn sterol (SBS) against acute liver injury induced by carbon tetrachloride (CCl4) in rats. Five-week-old male Sprague-Dawley (SD) rats were divided into six groups and fed with saline (Group BG), 50% CCl4 (Group MG), or bifendate 200 mg/kg (Group DDB), or treated with low-dose (Group LD), medium-dose (Group MD), or high-dose (Group HD) SBS. This study, for the first time, observed the protection of SBS against CCl4-induced liver injury in rats and its underlying mechanisms. Investigation of enzyme activities showed that SBS-fed rats exhibited a significant alleviation of inflammatory lesions, as evidenced by the decrease in cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and gamma-glutamyl transpeptidase (γ-GT). In addition, compared to the MG group, the increased indices (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), total antioxidant capacity (T-AOC), and total protein (TP)) of lipid peroxidation and decreased malondialdehyde (MDA) in liver tissues of SBS-treated groups showed the anti-lipid peroxidation effects of SBS. Using the wide range of targeted technologies and a combination of means (UPLC-MS/MS detection platform, self-built database, and multivariate statistical analysis), the addition of SBS was found to restore the expression of metabolic pathways (e.g., L-malic acid, N-acetyl-aspartic acid, N-acetyl-l-alanine, etc.) in rats, which means that the metabolic damage induced by CCl4 was alleviated. Furthermore, transcriptomics was employed to analyze and compare gene expression levels of different groups. It showed that the expressions of genes (Cyp1a1, Noct, and TUBB6) related to liver injury were regulated by SBS. In conclusion, SBS exhibited protective effects against CCl4-induced liver injury in rats. The liver protection mechanism of SBS is probably related to the regulation of metabolic disorders, anti-lipid peroxidation, and inhibition of the inflammatory response.

Effects of medical plants from Zingiberaceae family on cardiovascular risk factors of type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials.

We performed a meta-analysis on randomized controlled trials (RCTs) to evaluate the efficacy of Zingiberaceae on cardiovascular risk factors in type 2 diabetes mellitus (T2DM). PubMed, Web of Science, Embase, The Cochrane Library, and Scopus were searched systematically until October 18, 2021. Thirty-four RCTs with 2154 patients met our inclusion. Pooled analysis indicated that Zingiberaceae can significantly improve body weight (BW) (WMD = -1.012, 95% CI: -1.673, -0.351, p = .003), fasting blood glucose (FBG) (WMD = -14.292, 95% CI: -18.588, -9.995, p < .001), glycosylated hemoglobin 1c (HbA1c) (WMD = -0.432, 95% CI: -0.607, -0.257, p < .001), serum insulin (WMD = -2.036, 95% CI: -2.857, -1.216, p < .001), homeostasis model assessment insulin resistance (HOMA-IR) (WMD = -0.886, 95% CI: -1.375, -0.398, p < .001), high density lipoprotein-cholesterol (HDL-C) (WMD = 0.850, 95% CI: 0.018, 1.682, p = .045), triglyceride (TG) (WMD = -17.636, 95% CI: -27.121, -8.151, p < .001), diastolic blood pressure (DBP) (WMD = -0.642, 95% CI: -1.148, -0.137, p = .013), C-reactive protein (CRP) (WMD = -0.623, 95% CI: -1.061, -0.186, p = .005), tumor necrosis factor-α (TNF-α) (WMD = -3.020, 95% CI: -4.327, -1.712, p < .001), and interleukin 6 (IL-6) (WMD = -1.147, 95% CI: -1.887, -0.406, p = .002). The supplementation of Zingiberaceae may be an effective adjunctive therapy in management of T2DM and prevention cardiovascular complications by decreasing BW, improving blood glucose control, insulin resistance, lipid profiles (HDL-C and TG), blood pressure (DBP), and reducing inflammation (CRP, TNF-α, and IL-6). PRACTICAL APPLICATIONS: Approximately half of the deaths of individuals with diabetes mellitus (DM) are attributable to cardiovascular disease (CVD), and individuals with T2DM have a two-fold increased risk of cardiovascular mortality than healthy individuals. Currently, T2DM is mainly treated with hypoglycemic medication such as sulfonylureas, thiazolidinediones, meglitinides, and biguanides. Nevertheless, most of them with long-term usage could cause side effects, including hypoglycemia and gastrointestinal troubles. Several species of the Zingiberaceae family are used in traditional herbal medicines, which have been widely used in traditional and complementary medicine. Proving the potential benefits of Zingiberaceae on T2DM and its cardiovascular complications has positive clinical implications for the use of this practical herb.