Medicinal Mushrooms and Their Use to Strengthen Respiratory Health during and Post-COVID-19 Pandemic.

COVID-19 infection has been a key threat to the public health system globally, with an estimated 248 million cases worldwide. COVID-19 patients are subject to a higher risk of developing chronic respiratory disorders that are closely associated with long-term disability, multi-morbidity, and premature mortality. Although there have been recent advancements in respiratory treatment regimens, there has also been increased interest in the use of medicinal mushrooms in bridging the unaddressed pathways of action within the treatment algorithms. In this review, we provide a collection of medicinal mushrooms that are beneficial in promoting respiratory health and potentially reducing COVID-19 symptoms in patients who are newly diagnosed and those who have recovered. While reviewing the use of immunomodulatory pathways, which have shown promising results in tackling side effects and post-COVID syndromes, we also provide insights into how the antioxidant elements present in medicinal mushrooms help to achieve the same results, especially in the prophylactic and therapeutic management of COVID-19 infection. To date, medicinal mushrooms are regarded as a functional food, which, however, need further quality, safety, and efficacy assessments. These requirements are also highlighted in the present review to promote the future development and application of medicinal mushrooms for better respiratory health.

Synthesis of ginsenoside Rb1-imprinted magnetic polymer nanoparticles for the extraction and cellular delivery of therapeutic ginsenosides.

Background: Panax ginseng (ginseng) is a traditional medicine that is reported to have cardioprotective effects; ginsenosides are the major bioactive compounds in the ginseng root. Methods: Magnetic molecularly imprinted polymer (MMIP) nanoparticles might be useful for both the extraction of the targeted (imprinted) molecules, and for the delivery of those molecules to cells. In this work, plant growth regulators were used to enhance the adventitious rooting of ginseng root callus; imprinted polymeric particles were synthesized for the extraction of ginsenoside Rb1 from root extracts, and then employed for subsequent particle-mediated delivery to cardiomyocytes to mitigate hypoxia/reoxygenation injury. Results: These synthesized composite nanoparticles were first characterized by their specific surface area, adsorption capacity, and magnetization, and then used for the extraction of ginsenoside Rb1 from a crude extract of ginseng roots. The ginsenoside-loaded MMIPs were then shown to have protective effects on mitochondrial membrane potential and cellular viability for H9c2 cells treated with CoCl2 to mimic hypoxia injury. The protective effect of the ginsenosides was assessed by staining with JC-1 dye to monitor the mitochondrial membrane potential. Conclusion: MMIPs can play a dual role in both the extraction and cellular delivery of therapeutic ginsenosides.

Effect of Guided Imagery Meditation During Laparoscopic Cholecystectomy on Reducing Anxiety: A Randomized Controlled Trial.

BACKGROUND: Up to 90% of patients still experience pain after abdominal surgery, which also affects their physical recovery and psychological anxiety. AIM: To evaluate the effects of guided imagery meditation on ameliorating anxiety, improving the quality of sleep, and relieving postoperative pain in patients after laparoscopic cholecystectomy surgery. METHOD: In the general surgical ward of a teaching hospital, patients were randomly assigned to usual care (n = 34) and guided imagery meditation intervention (n = 34) groups, using the method. The measuring outcomes included their anxiety score, quality of sleep, and pain control. RESULTS: In terms of the anxiety difference, the experimental group scored 0.42 (standard deviation [SD] = 0.97), while the control group scored 4.79 (SD = 7.56), which indicates a statistically significant difference (F = 8.04, p = .01, partial eta2 = 0.11). In terms of quality of sleep, the mean score of the experimental group was 2.67 (SD = 1.96), while the control group scored 7.55 (SD = 3.81), which indicates a significant difference (F = 39.99, p = .001, partial eta2 = 0.39). The mean of the degree of postoperative pain was 2.11 points (SD = 1.39), and the score of the control group was 4.00 points (SD = 1.62), which indicates a significant difference (p = .001). CONCLUSIONS: Guided imagery meditation is a simple, non-invasive, non-pharmacologic intervention measure. It can reduce anxiety and postoperative pain, and improve the quality of sleep. Thus, it should be promoted in clinical practice.

A Review of the Potential Effects of Melatonin in Compromised Mitochondrial Redox Activities in Elderly Patients With COVID-19.

Melatonin, an endogenous indoleamine, is an antioxidant and anti-inflammatory molecule widely distributed in the body. It efficiently regulates pro-inflammatory and anti-inflammatory cytokines under various pathophysiological conditions. The melatonin rhythm, which is strongly associated with oxidative lesions and mitochondrial dysfunction, is also observed during the biological process of aging. Melatonin levels decline considerably with age and are related to numerous age-related illnesses. The signs of aging, including immune aging, increased basal inflammation, mitochondrial dysfunction, significant telomeric abrasion, and disrupted autophagy, contribute to the increased severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. These characteristics can worsen the pathophysiological response of the elderly to SARS-CoV-2 and pose an additional risk of accelerating biological aging even after recovery. This review explains that the death rate of coronavirus disease (COVID-19) increases with chronic diseases and age, and the decline in melatonin levels, which is closely related to the mitochondrial dysfunction in the patient, affects the virus-related death rate. Further, melatonin can enhance mitochondrial function and limit virus-related diseases. Hence, melatonin supplementation in older people may be beneficial for the treatment of COVID-19.

Chinese Caterpillar Mushroom, Ophiocordyceps sinensis (Ascomycota), Cold-Water Extract Relaxes the Rat Isolated Bladder.

Ophiocordyceps sinensis is a popular medicinal mushroom used for various health conditions, including alleviation of frequent urination, which is a major symptom of overactive bladder (OAB) syndrome. This study aimed to investigate the effect of O. sinensis (OCS02 cultivar) cold-water extract (CWE) against bladder contractility using the organ bath technique. The bladder was removed from male Sprague-Dawley rats and cut into longitudinal strips of 2 mm × 8 mm. In some experiments, the urothelium was removed to study its role in CWE-induced responses. CWE elicited a biphasic response consisting of an immediate, transient contraction that was followed by a sustained relaxation in bladder strips precontracted with carbachol, a muscarinic agonist. Removal of urothelium did not alter the magnitude of the contractile response but significantly attenuated the relaxation response. In the presence of L-NAME (nitric oxide synthase inhibitor) and sodium nitroprusside (nitric oxide donor), CWE-induced transient contraction was enhanced, whereas the relaxation response was significantly reduced. Following preincubation with CWE, the amplitude and the frequency of the spontaneous myogenic contractions induced by carbachol, as well as the contractile response toward calcium, were significantly suppressed. Findings from this study show that the urothelium plays a role in the relaxant effect of CWE. Its mechanisms of action include the regulation of nitric oxide and inhibition of calcium influx.

A bibliometric analysis on the tribological and physicochemical properties of vegetable oil-based bio-lubricants (2010-2021).

Vegetable oil-based bio-lubricants possess potential as an alternative to mineral oil-based lubricants due to their biodegradability and renewability. However, a detailed examination of the publication focus, trend, and future direction related to these bio-lubricants' tribological and physicochemical properties is scarce. Therefore, the study presents a bibliometric analysis of vegetable oil-based bio-lubricant. One hundred sixty-five publications were extracted from Web of Science (WoS) from 2010 to 2021. During this period, the total citation was 2,240, recording an average citation per publication of 13.58. Proceedings of The Institution of Mechanical Engineers, Part J: Journal of Engineering Tribology was the top productive journal, publishing 10.3% of the publications selected on the studied topic. From 2010 to 2021, India was the most productive country working on bio-lubricants due to its abundance of coconut products, followed by Malaysia due to its abundance of palm products. The keyword analysis indicated that a significant amount of work emphasised the derivation of bio-lubricants with an increasing shift towards tribological performance characterisation. From the analysis, palm is the most studied bio-lubricant, followed by castor oil. The reported viscosity and viscosity index values cover an extensive range, allowing these bio-lubricants to be adopted for a wide range of applications. For different vegetable oil-based bio-lubricants, the coefficient of friction is reported from 0.001 to 0.78, with the wear scar diameter being reported from 0.075 µm to 4.59 mm. Even though these bio-lubricants' friction and wear performances can be tabulated, the dataset is still unreliable for lubricant-selection purposes because of the varying test conditions. Such a scenario also limits the ability to correlate the role of fatty acid composition in the vegetable oil-based bio-lubricants in fulfilling their various application-specific potentials. Therefore, this study recommends that a unified correlation between the fatty acid composition and its tribological performance be attained consistently to better elucidate the potential of vegetable oil-based bio-lubricants.

Efficacy and safety of Duhuo Jisheng Decoction add-on bisphosphonate medications in patients with osteoporosis: A meta-analysis of randomized controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: Duhuo Jisheng Decoction (DHJSD) is the most frequently prescribed herbal formula for the treatment of osteoporosis. However, efficacy and safety of DHJSD add-on bisphosphonate medications remain unclear. AIM OF THE STUDY: The purpose of this study was to reveal efficacy and safety of DHJSD add-on bisphosphonate medications in patients with osteoporosis through a systematic review with meta-analysis of randomized controlled trials (RCTs). METHODS: Five important databases were searched for RCTs on this topic, and two authors individually extracted information and data concerning study design, baseline characteristics, efficacy rate, bone mineral density (BMD), pain score, and adverse event. Meta-analysis was done mainly with risk ratio (RR) and standardized mean difference (SMD) for BMD and pain, using random-effects model; while Peto odds ratios (PORs) were used for pooling adverse event rates due to sparse data. Point estimate was reported with 95% confidence intervals (CIs). RESULTS: Seventeen RCTs (n = 1526) met eligibility criteria, and were included in this synthesis. Pooled estimates demonstrated that as compared with no DHJSD, DHJSD-B led to significantly higher efficacy rates (RR = 1.25, 95%CI: 1.19-1.31; I2 = 0%), more lumbar BMD (SMD = 0.61, 95%CI: 0.25-0.96; I2 = 20%), lower pain score (SMD = -1.10, 95%CI: 1.40-0.79; I2 = 33%), and lower overall adverse event rates (POR = 0.40; 95%CI: 0.20-0.97; I2 = 27%). CONCLUSION: Adding DHJSD on bisphosphonate medications seems to be an effective and safe strategy in treating patients with osteoporosis.

Porous Biphasic Calcium Phosphate Granules from Oyster Shell Promote the Differentiation of Induced Pluripotent Stem Cells.

Oyster shells are rich in calcium, and thus, the potential use of waste shells is in the production of calcium phosphate (CaP) minerals for osteopathic biomedical applications, such as scaffolds for bone regeneration. Implanted scaffolds should stimulate the differentiation of induced pluripotent stem cells (iPSCs) into osteoblasts. In this study, oyster shells were used to produce nano-grade hydroxyapatite (HA) powder by the liquid-phase precipitation. Then, biphasic CaP (BCP) bioceramics with two different phase ratios were obtained by the foaming of HA nanopowders and sintering by two different two-stage heat treatment processes. The different sintering conditions yielded differences in structure and morphology of the BCPs, as determined by scanning electron microscopy (SEM), X-ray diffraction (XRD), and Brunauer-Emmett-Teller (BET) surface area analysis. We then set out to determine which of these materials were most biocompatible, by co-culturing with iPSCs and examining the gene expression in molecular pathways involved in self-renewal and differentiation of iPSCs. We found that sintering for a shorter time at higher temperatures gave higher expression levels of markers for proliferation and (early) differentiation of the osteoblast. The differences in biocompatibility may be related to a more hierarchical pore structure (micropores within macropores) obtained with briefer, high-temperature sintering.

N, N-dimethylglycine Protects Behavioral Disturbances and Synaptic Deficits Induced by Repeated Ketamine Exposure in Mice.

Ketamine, an N-methyl-d-aspartate receptor (NMDAR) blocker, is gaining ground as a treatment option for depression. The occurrence of persistent psychosis and cognitive impairment after repeated use of ketamine remains a concern. N, N-dimethylglycine (DMG) is a nutrient supplement and acts as an NMDAR glycine site partial agonist. The objective of this study was to assess whether DMG could potentially prevent the behavioral and synaptic deficits in mice after repeated ketamine exposure. Male ICR mice received ketamine (20 mg/kg) from postnatal day (PN) 33-46, twice daily, for 14 days. The locomotor activity, novel location recognition test (NLRT), novel object recognition test (NORT), social interaction test, head twitch response induced by serotonergic hallucinogen, and the basal synaptic transmission and long-term potentiation (LTP) in the hippocampal slices were monitored after repeated ketamine treatment. Furthermore, the protective effects of repeated combined administration of DMG (30 and 100 mg/kg) with ketamine on behavioral abnormalities and synaptic dysfunction were assessed. The results showed that mice exhibited memory impairments, social withdrawal, increased head twitch response, reduced excitatory synaptic transmission, and lower LTP after repeated ketamine exposure. The ketamine-induced behavioral and synaptic deficits were prevented by co-treatment with DMG. In conclusion, these findings may pave a new path forward to developing a combination formula with ketamine and DMG for the treatment of depression and other mood disorders.

Suppression of Inflammatory and Fibrotic Signals by Cinnamon (Cinnamomum cassia) and Cinnamaldehyde in Cyclophosphamide-Induced Overactive Bladder in Mice.

Cinnamon (Cinnamomum cassia) is a well-known traditional Chinese medicine used to treat nocturia by tonifying and warming the kidney. Our recent clinical study found that overactive bladder (OAB) patients treated with cinnamon powder (CNP) patches exhibited significantly ameliorated OAB symptoms without significant side effects, but the mechanism of action is unclear. To explore the beneficial effects and action mechanisms of CNP and its major active component cinnamaldehyde (CNA) in an OAB-related murine model, cyclophosphamide- (CYP-) induced OAB injury was performed on male ICR mice in the presence or absence of CNP and CNA, as well as solifenacin, a clinical drug for OAB as a reference. Twenty-four-hour micturition patterns (frequency of urination and volume of urine per time), as well as histopathological examination, immunohistochemistry (IHC), and Western blotting of the bladder, were analyzed for mechanism elucidation. Administration of CYP (300 mg/kg, i.p.) induced typical OAB pathophysiological changes, including increased frequency of urination and reduced volume of urine. CYP-induced mice displayed strong edema of the bladder and hemorrhagic cystitis, accompanied by loss of normal corrugated folds and decreased muscarinic receptors (M2/M3) in the urothelium, and disordered/broken structures of the lamina propria and detrusor. These changes were correlated with increased leukocyte (CD11b) infiltration colocalized with inflammatory (pp65 NFκB, macrophage migration inhibitory factor (MIF)/Toll-like receptor 4 (TLR4)) and fibrotic (stem cell factor (SCF)/c-Kit, α-smooth muscle actin (α-SMA)/ß-catenin) signals. Treatment with CNP (600 mg/kg, p.o.) and CNA (10-50 mg/kg, p.o.), but not solifenacin (50 mg/kg), 30 min after CYP induction significantly ameliorated CYP-induced dysfunction in micturition patterns and pathophysiological changes. CNP and CNA further suppressed MIF/TLR4-associated inflammatory and SCF/c-Kit-related fibrotic signaling pathways. Our findings indicate that suppression of inflammatory and fibrotic signals contributes to the crucial mechanism in the improvement of CYP-induced OAB by CNP and CNA.

Cost-effectiveness analysis of rivaroxaban plus aspirin versus aspirin alone in secondary prevention among patients with chronic cardiovascular diseases.

PURPOSE: This study aimed to investigate the cost-effectiveness of low-dose rivaroxaban plus aspirin versus aspirin alone for patients with stable cardiovascular diseases in the Taiwan setting. METHODS: We constructed a Markov model to project the lifetime direct medical costs and quality-adjusted life-years of both therapies. Transitional probabilities were derived from the COMPASS trial, and the costs and utilities were obtained from the Taiwan National Health Insurance Database and published studies. One-way, scenario, subgroup, and probabilistic sensitivity analyses were performed to assess the uncertainty. Incremental cost-effectiveness ratio was presented as the outcome. The threshold of willingness-to-pay was set at US$76,368 (3 times the gross domestic product per capita of Taiwan). All analyses were operated by TreeAge 2019 and Microsoft Excel. RESULTS: The incremental cost-effectiveness ratios of rivaroxaban plus aspirin versus aspirin alone in the patients with stable cardiovascular diseases, coronary artery diseases, and peripheral artery diseases were US$83,459, US$69,852 and -US$13,823 per quality-adjusted life-year gained, respectively. The probabilistic sensitivity analyses showed that the probabilities of cost-effectiveness for the regimen with rivaroxaban among those with cardiovascular diseases and coronary artery diseases were 44.1% and 65.3% at US$76,368. CONCLUSION: Low-dose rivaroxaban plus aspirin is less likely to be a cost-effective alternative to aspirin in secondary prevention for the patients with stable cardiovascular diseases; however, among these patients, the regimen may have pharmacoeconomic incentives for the group merely having chronic coronary artery diseases from the Taiwan national payer's perspective. The pharmacoeconomic incentives are influenced by the drug price, event treatment fees, and willingness-to-pay threshold.

In vivo and in vitro evaluation of the osteogenic potential of Davallia mariesii T. Moore ex Baker.

ETHNOPHARMACOLOGICAL RELEVANCE: Postmenopausal osteoporosis is a major bone health issue worldwide. There is an unmet medical need for osteoporosis treatments, a disease which disproportionately impacts women. Exploring botanicals to prevent or treat osteoporosis is currently an interest of investigations. Rhizomes of Davallia mariesii T. Moore ex Baker (Davalliacea) are used an indigenous herbal medicine in Asia for injuries due to fractures, contusions, and strains. AIM OF THE STUDY: In the present study, we investigated the osteogenic effect of the water extract of rhizomes of D. mariesii (DMH) on bone loss induced by an ovariectomy (OVX) in mice and also its impact on osteogenesis in primary human osteoblasts (HObs). Additionally, we performed a quantitative analysis of compounds in the DMH extract. MATERIALS AND METHODS: OVX C57BL/6J mice were orally administrated DMH extract for 12 weeks, and microarchitecture parameters were examined by microcomputed tomography. DMH extract was fractionated in a bio-guided manner, and fractions were isolated to obtain active compounds using HObs. Cell viability was evaluated by an MTT assay. Characteristics of early and late osteogenesis were analyzed by alkaline phosphatase activity and a mineralization assay. Molecular mechanisms were explored by a real-time quantitative PCR. Compounds in the DMH extract were identified and quantified using liquid chromatography tandem mass spectroscopy (LC-MS/MS). RESULTS: DMH improved bone mineral densities of vertebrae and the femur. Through microarchitectural observations, DMH significantly decreased the bone surface/volume ratio and trabecular separation, and also increased the connectivity density in the OVX group. Additionally, DMH inhibited osteoclast differentiation in receptor activator of nuclear factor-κB ligand-induced osteoclasts and increased bone formation in HObs. After bio-guided fractionation and isolation, we found that eriodictyol-7-O-ß-d-glucuronide (2) significantly increased alkaline phosphatase activity, and 5-O-ß-d-(6-O-vanilloylglucopyranosyl)gentisic acid (3) substantially enhanced mineral deposition. In HObs, compound 3 was more potent in upregulating expressions of bone morphogenetic protein-2, bone sialoprotein, osteopontin, osterix, and estrogen receptor-α. The amount of bioactive compound 3 in DMH was 5.68 ±â€¯0.64 mg/g of dry weight according to LC-MS/MS. CONCLUSION: For the first time we report that D. mariesii and its isolated compounds demonstrated potent osteogenic activities. Quantitative results of D. mariesii could be a reference for phytochemical analyses.

Efficacy of cinnamon patch treatment for alleviating symptoms of overactive bladder: A double-blind, randomized, placebo-controlled trial.

BACKGROUND: Current treatments for overactive bladder (OAB) have limited efficacy, low persistence and a high rate of adverse events commonly leading to treatment cessation in clinical practice. Clinicians in Asia commonly use traditional Chinese medicine as an alternative for OAB treatment despite it having uncertain efficacy and safety. To evaluate the efficacy and safety of cinnamon patch (CP) treatment for alleviating symptoms of OAB, a double-blind randomized, placebo-controlled trial was conducted in the present study. MATERIALS AND METHODS: In this 6-week randomized clinical trial conducted in an outpatient setting, 66 subjects diagnosed as having OAB were enrolled and treated with a placebo (n=33) or CP (n=33). The OAB symptom score (OABSS) was selected as the primary end point, and a patient perception of bladder condition (PPBC), an urgency severity scale (USS), and post-voiding residual urine (PVR) volume were selected as secondary end points. Statistical analyses were performed with IBM SPSS Statistics 20. Groups were compared using an independent sample t-test, Fisher exact test, and Chi-squared test. RESULTS: In total, 66 participants (40 women and 26 men), 60.35 ± 12.77 years of age, were included in the intention-to-treat analyses. Baseline characteristics were comparable between the CP (n ==33) and placebo (n ==33) groups. Treatment with a CP showed statistically significant differences in reductions in OABSS scores (9.70 ± 2.20 to 6.33 ± 2.42), PPBC scores (3.36 ± 0.60 to 2.15 ± 0.83), and USS scores (2.67 ± 0.54 to 1.64 ± 0.60). CONCLUSIONS: Compared to a placebo, treatment with CP might be considered an effective and safe complementary therapy for OAB. Further studies employing a positive control, different dosage forms, larger sample sizes, and longer treatment periods are warranted.

The effectiveness of far-infrared irradiation on foot skin surface temperature and heart rate variability in healthy adults over 50 years of age: A randomized study.

BACKGROUND: Far-infrared irradiation (FIR) is used in the medical field to improve wound healing, hemodialysis with peripheral artery occlusive disease, and osteoarthritis but seldom used in ameliorating poor lower extremity circulation. The purpose of this study was to evaluate the effect of FIR on changes in foot skin surface temperature (FSST) and autonomic nerve system (ANS) activity to evaluate its effectiveness in improving lower limb circulation. METHODS: A randomized controlled study was conducted. Subjects (n = 44), all over the age of 50 years and satisfying the inclusion criteria, were randomly allocated into 2 groups. The intervention group received FIR on a lower limb for 40 minutes and the control group received no intervention. Left big toe (LBT), right big toe (RBT), left foot dorsal (LFD), right foot dorsal (RFD) surface skin temperature, autonomic nervous activity, and blood pressure were assessed. RESULTS: The main results were skin surface temperature at the LBT increased from 30.8 ±â€Š0.4°C to 34.8 ±â€Š0.4°C, at RBT increased from 29.6 ±â€Š0.4°C to 35.3 ±â€Š0.4°C and LFD increased from 31.9 ±â€Š0.3°C to 36.4 ±â€Š0.4°C, RFD increased from 30.7 ±â€Š0.3°C to 37.7 ±â€Š0.2°C. FIR caused a significant increase of the FSST ranging in a 4°C to 7°C increase after 40 minutes irradiation (P < .001). The ANS low-frequency (LF) and high-frequency (HF) activity showed a statistically significant increase in the FIR group (P < .05) but not the LF/HF ratio. CONCLUSION: FIR significantly increased the FSST from between 4°C and 7°C after 40 minutes irradiation, which might improve lower extremity circulation and regulation of ANS activity.

Comprehensive LC-MS/MS-based phytochemical perspectives and osteogenic effects of Uraria crinita.

Osteogenesis plays a vital role in the maintenance of bone health. Imbalances in osteogenesis influence the onset of several bone loss-associated diseases. The intake of Uraria crinita (Fabaceae) through dietary supplements is advised for childhood bone dysplasia. This botanical provides edible tonics and detoxifiers, and is also used as a folk beverage. We evaluated the osteogenic effects of a 50% ethanol extract of the root of U. crinita on primary human osteoblasts (HObs) and initiated a novel comprehensive phytochemical strategy using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for quality control of this functional food. Two isoflavones, genistein (5) and 5,7-dihydroxy-3',5'-dihydroxyisoflavone (6), increased the alkaline phosphatase activity (differentiation stage); the flavone glycoside vitexin (1), and the phenolic acid salicylic acid (2) enhanced the mineralization (mature stage). The isoflavone 2'-hydroxygenistein (4) possessed high osteogenic potential among the isolated compounds in HObs. It promoted osteogenesis-related stages and upregulated the gene expressions in a dose-dependent manner. The major compounds in the active fraction were quantitatively analyzed via phytochemical fingerprint detection. These LC-MS/MS-based phytochemical perspectives can act as reference standards in developing food supplements from U. crinita.

In vitro and in vivo evaluation of the neuroprotective activity of Uncaria hirsuta Haviland.

The incidence of neurodegeneration leading to the conditions such as Alzheimer's and Parkinson's diseases are on the increase, they require the approaches that focus on protection prevention rather than treatment. Plants are rich sources of many compounds which possess medicinal properties. We sought to investigate the neuroprotective effects of Uncariahirsuta and its compounds on d-galactose-induced stress in BALB/c mice as well as 6-hydroxydopamine (6-OHDA)-induced stress in mouse nerve growth factor (mNGF)-differentiated PC12 cells. Our results demonstrate that the 95% ethanol extract of U. hirsuta reversed the d-galactose-induced learning and memory dysfunctions and decreased the malodialdehyde levels. Furthermore, the isolated compounds, 5ß-carboxystrictosidine (1) and chlorogenic acid (2), protected mNGF-differentiated PC12 cells against toxicity induced by 6-OHDA by acting as antiapoptotic agents. The 50% inhibitory concentration (IC50) for intracellular reactive oxygen species (ROS) scavenging was found to be 24.5 (for 1) and 19.7 µM (for 2), and both 1 and 2 reduced intracellular calcium levels with respective IC50 values of 46.9 and 27 µM. Interestingly, both compounds inhibited caspase 3 and 9 activities with respective IC50 values of 25.6 and 24.5 µM for 1 and 19.4 and 16.3 µM for 2. Our results identify U. hirsuta and its active compounds as potential neuroprotective agents and deserve further evaluation for drug development for neuroprotection in the future.

Unlocking the Mystery of the Therapeutic Effects of Chinese Medicine on Cancer.

Over the past decade, the rise of cancer immunotherapy has coincided with a remarkable breakthrough in cancer therapy, which attracted increased interests in public. The scientific community clearly showed that the emergence of immunotherapy is an inevitable outcome of a holistic approach for cancer treatment. It is well established that traditional Chinese medicine (TCM) utilizes the principle of homeostasis and balance to adjust the healthy status of body. TCM treatment toward cancer has a long history, and the diagnosis and treatment of tumors were discussed in the ancient and classical literatures of Chinese medicine, such as the Yellow Emperor's Inner Canon. Precious heritage has laid the foundation for the innovation and development of cancer treatment with TCM. The modern study indicated that TCM facilitates the treatment of cancer and enhances the survival rate and life expectancy of patients. However, the pharmacological mechanisms underlying these effects are not yet completely understood. In addition, physicians cannot always explain why the TCM treatment is effective and the mechanism of action cannot be explained in scientific terms. Here, we attempted to provide insights into the development of TCM in the treatment and interpret how TCM practitioners treat cancer through six general principles of TCM by using modern scientific language and terms based on newly discovered evidence.

Exploration of Medical Trajectories of Stroke Patients Based on Group-Based Trajectory Modeling.

A high mortality rate is an issue with acute cerebrovascular disease (ACVD), as it often leads to a high medical expenditure, and in particular to high costs of treatment for emergency medical conditions and critical care. In this study, we used group-based trajectory modeling (GBTM) to study the characteristics of various groups of patients hospitalized with ACVD. In this research, the patient data were derived from the 1 million sampled cases in the National Health Insurance Research Database (NHIRD) in Taiwan. Cases who had been admitted to hospitals fewer than four times or more than eight times were excluded. Characteristics of the ACVD patients were collected, including age, mortality rate, medical expenditure, and length of hospital stay for each admission. We then performed GBTM to examine hospitalization patterns in patients who had been hospitalized more than four times and fewer than or equal to eight times. The patients were divided into three groups according to medical expenditure: high, medium, and low groups, split at the 33rd and 66th percentiles. After exclusion of unqualified patients, a total of 27,264 cases (male/female = 15,972/11,392) were included. Analysis of the characteristics of the ACVD patients showed that there were significant differences between the two gender groups in terms of age, mortality rate, medical expenditure, and total length of hospital stay. In addition, the data were compared between two admissions, which included interval, outpatient department (OPD) visit after discharge, OPD visit after hospital discharge, and OPD cost. Finally, the differences in medical expenditure between genders and between patients with different types of stroke-ischemic stroke, spontaneous intracerebral hemorrhage (sICH), and subarachnoid hemorrhage (SAH)-were examined using GBTM. Overall, this study employed GBTM to examine the trends in medical expenditure for different groups of stroke patients at different admissions, and some important results were obtained. Our results demonstrated that the time interval between subsequent hospitalizations decreased in the ACVD patients, and there were significant differences between genders and between patients with different types of stroke. It is often difficult to decide when the time has been reached at which further treatment will not improve the condition of ACVD patients, and the findings of our study may be used as a reference for assessing outcomes and quality of care for stroke patients. Because of the characteristics of NHIRD, this study had some limitations; for example, the number of cases for some diseases was not sufficient for effective statistical analysis.

Isolated Compounds from Turpinia formosana Nakai Induce Ossification.

Bone metabolism is a homeostatic process, imbalance in which leads to the onset of diseases such as osteoporosis and osteopenia. Although several drugs are currently available to treat such conditions, they are associated with severe side effects and do not enhance bone formation. Thus, identifying alternative treatment strategies that focus on enhancing bone formation is essential. Herein, we explored the osteogenic potential of Turpinia formosana Nakai using human osteoblast (HOb) cells. The plant extract was subjected to various chromatographic techniques to obtain six compounds, including one new compound: 3,3'-di-O-methylellagic acid-4-O-α-l-arabinofuranoside (1). Compounds 3,3'-di-O-methylellagic acid-4-O-α-l-arabinofuranoside (1), gentisic acid 5-O-ß-d-(6'-O-galloyl) glucopyranoside (2), strictinin (3), and (-)-epicatechin-3-O-ß-d-allopyranoside (6) displayed no significant cytotoxicity toward HOb cells, and thus their effects on various osteogenic markers were analyzed. Results showed that 1-3 and 6 significantly increased alkaline phosphatase (ALP) activity up to 120.0, 121.3, 116.4, and 125.1%, respectively. Furthermore, 1, 2, and 6 also markedly enhanced the mineralization process with respective values of up to 136.4, 118.9, and 134.6%. In addition, the new compound, 1, significantly increased expression levels of estrogen receptor-α (133.4%) and osteogenesis-related genes of Runt-related transcription factor 2 (Runx2), osteopontin (OPN), bone morphogenetic protein (BMP)-2, bone sialoprotein (BSP), type I collagen (Col-1), and brain-derived neurotropic factor (BDNF) by at least 1.5-fold. Our results demonstrated that compounds isolated from T. formosana possess robust osteogenic potential, with the new compound, 1, also exhibiting the potential to enhance the bone formation process. We suggest that T. formosana and its isolated active compounds deserve further evaluation for development as anti-osteoporotic agents.

Cardamonin Induces Cell Cycle Arrest, Apoptosis and Alters Apoptosis Associated Gene Expression in WEHI-3 Mouse Leukemia Cells.

Cardamonin, the chalcone class, is one of the natural components from the spicy herbaceous plant (Alpinia conchigera Griff) and has anticancer activities in many human cancer cell lines. There is, however, no information to show that cardamonin induces cell apoptosis and alters apoptosis associated gene expressions in mouse leukemia cells. Thus, we investigated the effects of cardamonin on the apoptotic cell death and associated gene expression in mouse leukemia WEHI-3 cells in vitro. Results indicated that cardamonin decreased total viable cell number via induced cell morphological changes and apoptotic cell death in WEHI-3 cells that were assay by contrast-phase microscopy and flow cytometry examinations, respectively. The flow cytometry assay indicated that cardamonin increased reactive oxygen species (ROS) and Ca 2+ production, decreased the levels of mitochondrial membrane potential ( ΔΨm) and increased caspase-3, -8 and -9 activities in WEHI-3 cells. Western blotting was performed to analyze expression of relevant pro- and anti-apoptotic proteins and results showed that cardamonin decreased anti-apoptotic protein of Bcl-2 but increased pro-apoptotic protein of Bax in WEHI-3 cells. Furthermore, cardamonin increased cytochrome c, AIF and Endo G release, increased GRP78, caspase-12 that were associated with ER stress and increased Fas, Fas-Ligand and FADD expression. Furthermore, cardamonin increased the gene expressions of DAP (death-associated protein), TMBIM4 transmembrane (BAX inhibitor motif containing 4), ATG5 (autophagy related 5) but decreased the gene expression of DDIT3 (DNA-damage inducible transcript 3), DDIT4 (DNA-damage-inducible transcript 4), BAG6 (BCL2-associated athanogene 6), BCL2L13 [BCL2-like 13 (apoptosis facilitator)] and BRAT1 (BRCA1-associated ATM activator 1) that are associated with apoptosis pathways. Based on those findings, we may suggest cardamonin induced apoptotic cell death through Fas and Fas-Ligand-, caspase- and mitochondria-dependently pathways and also affects the apoptotic gene expression in WEHI-3 cells in vitro.