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Ginger has many bioactive compounds with pharmacological activities. However, few studies are known about these bioactive compounds activity in chemoresistant cells. The aim of the present study was to investigate the anticancer properties of ginger phytochemicals in docetaxel-resistant human prostate cancer cells in vitro. In this study, we isolated 6-gingerol, 10-gingerol, 4-shogaol, 6-shogaol, 10-shogaol, and 6-dehydrogingerdione from ginger. Further, the antiproliferation activity of these compounds was examined in docetaxel-resistant (PC3R) and sensitive (PC3) human prostate cancer cell lines. 6-gingerol, 10-gingerol, 6-shogaol, and 10-shogaol at the concentration of 100 μM significantly inhibited the proliferation in PC3R but 6-gingerol, 6-shogaol, and 10-shogaol displayed similar activity in PC3. The protein expression of multidrug resistance associated protein 1 (MRP1) and glutathione-S-transferase (GSTπ) is higher in PC3R than in PC3. In summary, we isolated the bioactive compounds from ginger. Our results showed that 6-gingerol, 10-gingerol, 6-shogaol, and 10-shogaol inhibit the proliferation of PC3R cells through the downregulation of MRP1 and GSTπ protein expression.

Chalcones belong to a class of biologically active polyphenolic natural products. As a result of their simple chemical nature, they are easily synthesized and show a variety of promising biological activities. 2-Hydroxy-4′-methoxychalcone (AN07) is a synthetic chalcone derivate with potential anti-atherosclerosis effects. In this study, we demonstrated the novel antioxidant, anti-inflammatory, and neuroprotective effects of AN07. In RAW 264.7 macrophages, AN07 attenuated lipopolysaccharide (LPS)-induced elevations in reactive oxygen species (ROS) level and oxidative stress via down-regulating gp91phox expression and stimulating the antioxidant system of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) pathways, which were accompanied by increased glutathione (GSH) levels. Additionally, AN07 attenuated LPS-induced inflammatory factors, including NO, inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and phosphorylated inhibitor of nuclear factor kappa B-alpha (p-IκBα) in RAW 264.7 macrophages. However, the effects of AN07 on promoting nuclear Nrf2 levels and decreasing COX-2 expressions were significantly abrogated by the peroxisome proliferator-activated receptor-γ (PPARγ) antagonist GW9662. In human dopaminergic SH-SY5Y cells treated with or without methylglyoxal (MG), a toxic endogenous by-product of glycolysis, AN07 up-regulated neurotrophic signals including insulin-like growth factor 1 receptor (IGF-1R), p-Akt, p-GSK3β, glucagon-like peptide 1 receptor (GLP-1R), and brain-derived neurotrophic factor (BDNF). AN07 attenuated MG-induced apoptosis by up-regulating the B-cell lymphoma 2 (Bcl-2) protein and down-regulating the cytosolic expression of cytochrome c. AN07 also attenuated MG-induced neurite damage via down-regulating the Rho-associated protein kinase 2 (ROCK2)/phosphorylated LIM kinase 1 (p-LIMK1) pathway. Moreover, AN07 ameliorated the MG-induced down-regulation of neuroprotective Parkinsonism-associated proteins parkin, pink1, and DJ-1. These findings suggest that AN07 possesses the potentials to be an anti-inflammatory, antioxidant, and neuroprotective agent

Hyperbaric oxygen therapy (HBOT) has been suggested as a potential adjunctive therapy for Parkinson’s disease (PD). PD is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The aim of this study was to investigate the protective mechanisms of HBOT on neurons and motor function in a 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD and 1-methyl-4-phenylpyridinium (MPP+)-mediated neurotoxicity in SH-SY5Y cells on the potential protective capability. In vivo: male C57BL/6 mice were randomly divided into three groups: control, MPTP group and MPTP+HBOT group. The MPTP-treated mice were intraperitoneally received MPTP (20 mg/kg) four times at 2 h intervals within a day. The day after MPTP treatment, MPTP+HBOT mice were exposed to hyperbaric oxygen at 2.5 atmosphere absolute (ATA) with 100% oxygen for 1 h once daily for 7 consecutive days. In vitro: retinoic acid (RA)-differentiated SH-SY5Y cells were treated with MPP+ for 1 h followed by hyperbaric oxygen at 2.5 ATA with 100% oxygen for 1 h. The results showed that MPTP induced a significant loss in tyrosine hydroxylase (TH)-positive neurons in the SNpc of mice. HBOT treatment significantly increased the number of TH-positive neurons, with enhanced neurotrophic factor BDNF, decreased apoptotic signaling and attenuated inflammatory mediators in the midbrain of MPTP-treated mice. In addition, MPTP treatment decreased the locomotor activity and grip strength of mice, and these effects were shown to improve after HBOT treatment. Furthermore, MPTP decreased mitochondrial biogenesis signaling (SIRT-1, PGC-1α and TFAM), as well as mitochondrial marker VDAC expression, while HBOT treatment was shown to upregulate protein expression. In cell experiments, MPP+ reduced neurite length, while HBOT treatment attenuated neurite retraction. Conclusions: the effects of HBOT in MPTP-treated mice might come from promoting mitochondrial biogenesis, decreasing apoptotic signaling and attenuating inflammatory mediators in the midbrain, suggesting its potential benefits in PD treatment.

Methylglyoxal (MG) acts as a reactive precursor of advanced glycation end products (AGEs). This compound is often connected with pathologies such as diabetes, neurodegenerative processes and diseases of aging. 2-iodo-4′-methoxychalcone (CHA79), a synthetic halogen-containing chalcone derivative, has been reported its anti-diabetic activity. This study aims to investigate the potential protective capability of CHA79 against MG-mediated neurotoxicity in SH-SY5Y cells. Results indicated CHA79 increased viability of cells and attenuated the rate of apoptosis in MG-exposed SH-SY5Y. CHA79 up-regulated expression of anti-apoptotic protein (Bcl-2) and down-regulated apoptotic proteins (Bax, cytochrome c, caspase-3, caspase-9). Moreover, CHA79 significantly up-regulated expression of neurotrophic factors, including glucagon-like peptide-1 receptor (GLP-1R), brain derived neurotrophic factor (BDNF), p75NTR, p-TrkB, p-Akt, p-GK-3β and p-CREB. CHA79 attenuated MG-induced ROS production and enhanced the antioxidant defense including nuclear factor erythroid 2-related factor 2 (Nrf2), HO-1, SOD and GSH. Furthermore, CHA79 attenuated MG-induced reduction of glyoxalase-1 (GLO-1), a vital enzyme on removing AGE precursors. In conclusion, CHA79 is the first novel synthetic chalcone possessing the GLP-1R and GLO-1 activating properties. CHA 79 also exhibits neuroprotective effects against MG toxicity by enhancing neurotrophic signal, antioxidant defense and anti-apoptosis pathway.

Mitochondrial dysfunction and energy imbalance caused by chemotherapy are key contributors to skeletal muscle atrophy, which severely impacts the quality of life in cancer patients. Paclitaxel, a commonly used chemotherapeutic agent, is known to promote muscle wasting and cellular senescence, largely by impairing mitochondrial function. In this study, we investigated the protective role of loganin, a naturally occurring iridoid glycoside, in preventing paclitaxel‐induced damage to skeletal muscle cells. Using C2C12 cells, we assessed whether loganin could counteract the harmful effects of paclitaxel. Our results demonstrated that loganin significantly improved cell viability and protected mitochondrial function, as reflected by better preservation of mitochondrial DNA content, membrane potential, and ATP production, while further enhancing mitochondrial biogenesis through upregulation of PGC‐1α, TFAM, and NRF1. In parallel, loganin activated metabolic regulators SIRT1 and AMPK, while restoring PDK4 expression, suggesting improved energy regulation. Additionally, glycogen levels and myotube morphology were maintained, alongside sustained myosin heavy chain expression. Loganin effectively reduced both cellular and mitochondrial reactive oxygen species and increased antioxidant defenses, including superoxide dismutase activity and glutathione levels. Notably, it also suppressed paclitaxel‐induced senescence and inflammation, as shown by decreased p21 expression, reduced NFκB phosphorylation, and lower levels of Cdkn1a and Il6 as well as reduced SA‐β‐gal staining. Overall, our findings demonstrate that loganin offers comprehensive protection against paclitaxel‐induced skeletal muscle injury by preserving mitochondrial function, supporting metabolic homeostasis, reducing oxidative stress, and limiting senescence. These results highlight the potential of loganin as a preventive adjunctive agent to mitigate chemotherapy‐related muscle toxicity.

The triterpenoid fraction of Ganoderma (Ganoderma triterpenoids, GTs) has been increasingly demonstrated to provide effective antioxidant, neuroprotective or cardioprotective activities. However, whether GTs is capable of perturbing the transmembrane ionic currents existing in electrically excitable cells is not thoroughly investigated. In this study, an attempt was made to study whether GTs could modify hyperpolarization-activated cation currents (Ih) in pituitary tumor (GH3) cells and in HL-1 atrial cardiomyocytes. In whole-cell current recordings, the addition of GTs produced a dose-dependent reduction in the amplitude of Ih in GH3 cells with an IC50 value of 11.7 µg/mL, in combination with a lengthening in activation time constant of the current. GTs (10 µg/mL) also caused a conceivable shift in the steady-state activation curve of Ih along the voltage axis to a more negative potential by approximately 11 mV. Subsequent addition of neither 8-cyclopentyl-1,3-dipropylxanthine nor 8-(p-sulfophenyl)theophylline, still in the presence of GTs, could attenuate GTs-mediated inhibition of Ih. In current-clamp voltage recordings, GTs diminished the firing frequency of spontaneous action potentials in GH3 cells, and it also decreased the amplitude of sag potential in response to hyperpolarizing current stimuli. In murine HL-1 cardiomyocytes, the GTs addition also suppressed the amplitude of Ih effectively. In DPCPX (1 µM)-treated HL-1 cells, the inhibitory effect of GTs on Ih remained efficacious. Collectively, the inhibition of Ih caused by GTs is independent of its possible binding to adenosine receptors and it might have profound influence in electrical behaviors of different types of electrically excitable cells (e.g., pituitary and heart cells) if similar in vitro or in vivo findings occur.

Background With the global rise in the aging population, ensuring safe mobility for older adults is an urgent public health concern. In Taiwan, scooters are widely used by older individuals, yet the impact of air pollution, particularly fine particulate matter (PM 2.5 ), on their traffic safety remains poorly understood. This study investigated the short-term association between PM 2.5 exposure and the risk of scooter collisions among older adults. Methods We conducted a nationwide time-series analysis using Taiwan’s Police-Reported Traffic Accident Registry and air quality monitoring data from 2023. The study included 58,181 scooter riders aged ≥ 65 years involved in collisions. Daily PM 2.5 concentrations were derived from over 70 monitoring stations. We applied distributed lag non-linear models (DLNM) with a negative binomial distribution to estimate the association between PM 2.5 exposure and daily scooter collision counts, adjusting for meteorological variables, co-pollutants (NO₂ and SO₂), and temporal variables. The models accounted for both same-day exposure and cumulative effect of exposure across lag periods of up to 14 days. Results We found that 159 older adults were involved in scooter collisions per day on average, with a mean PM 2.5 level of 13.4 µg/m³. A non-linear exposure-response relationship was observed, with rate ratios increased at PM 2.5 levels ≥ 20 µg/m³, particularly over longer lag periods. The highest risk estimate was observed for 15-day cumulative exposure at 31 µg/m³ (rate ratio = 2.357; 95% CI: 1.419–3.914). In contrast, same-day exposure showed a limited association with collision risk. Conclusions These findings suggest that prolonged exposure to elevated PM 2.5 may increase the risk of scooter collisions among older adults, highlighting the need to integrate air quality considerations into traffic safety strategies for aging populations.

Patients with cerebrovascular diseases often presented both cognitive and physical impairment. Disability in everyday functioning involving cognitive impairment among patients may be hard to completely rely on informants' reports, as their reports may be confounded with physical impairment. The aim of this study was to validate a performance-based measure of functional assessment, the Taiwan Performance-Based Instrumental Activities of Daily Living (TPIADL), for vascular cognitive impairment (VCI) by examining its psychometric properties and diagnostic accuracy. Ninety-seven patients with cerebrovascular diseases, including 30 with vascular dementia (VaD), 28 with mild cognitive impairment and 39 with no cognitive impairment, and 49 healthy control adults were recruited during study period. The TPIADL, as well as the Mini Mental State Examination (MMSE), Lawton-IADL and Barthel Index (BI), were performed. The internal consistency, convergent and criteria validity of the TPIADL were examined. Cronbach's alpha of the TPIADL test was 0.84. The TPIADL scores were significantly correlated with the Lawton IADL (r = -0.587, p <0.01). Notably, the TPIADL had a higher correlation coefficient with the cognitive domain of Lawton IADL (r = -0.663) than with physical domain of Lawton IADL (r = -0.541). The area under the relative operating characteristic curve was 0.888 (95% CI = 0.812-0.965) to differentiate VaD from other groups. The optimal cut-off point of the TPIADL for detecting VaD was 6/7, which gives a sensitivity of 73.3% and a specificity of 84.5%. The TPIADL is a brief and sensitive tool for the detection of IADL impairment in patients with VaD.

UCL-2077 (triphenylmethylaminomethyl)pyridine) was previously reported to suppress slow afterhyperpolarization in neurons. However, the information with respect to the effects of UCL-2077 on ionic currents is quite scarce. The addition of UCL-2077 decreased the amplitude of erg-mediated K+ current (IK(erg)) together with an increased deactivation rate of the current in pituitary GH3 cells. The IC50 and KD values of UCL-2077-induced inhibition of IK(erg) were 4.7 and 5.1 μM, respectively. UCL-2077 (10 μM) distinctly shifted the midpoint in the activation curve of IK(erg) to less hyperpolarizing potentials by 17 mV. Its presence decreased the degree of voltage hysteresis for IK(erg) elicitation by long-lasting triangular ramp pulse. It also diminished the probability of the opening of intermediate-conductance Ca2+-activated K+ channels. In cell-attached current recordings, UCL-2077 raised the frequency of action currents. When KCNH2 mRNA was knocked down, a UCL-2077-mediated increase in AC firing was attenuated. Collectively, the actions elaborated herein conceivably contribute to the perturbating effects of this compound on electrical behaviors of excitable cells.

Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by the gradual loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), resulting in reduced dopamine levels in the striatum and eventual onset of motor symptoms. Linalool (3,7-dimethyl-1,6-octadien-3-ol) is a monoterpene in aromatic plants exhibiting antioxidant, antidepressant, and anti-anxiety properties. The objective of this study is to evaluate the neuroprotective impacts of linalool on dopaminergic SH-SY5Y cells, primary mesencephalic and cortical neurons treated with 1-methyl-4-phenylpyridinium ion (MPP+), as well as in PD-like mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Cell viability, α-tubulin staining, western blotting, immunohistochemistry and behavioral experiments were performed. In MPP+-treated SH-SY5Y cells, linalool increased cell viability, reduced neurite retraction, enhanced antioxidant defense by downregulation of apoptosis signaling (B-cell lymphoma 2 (Bcl-2), cleaved caspase-3 and poly ADP-ribose polymerase (PARP)) and phagocyte NADPH oxidase (gp91phox), as well as upregulation of neurotrophic signaling (brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF)) and nuclear factor-erythroid 2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. In MPP+-treated primary mesencephalic neurons, linalool enhanced the expressions of tyrosine hydroxylase (TH), Sirtuin 1 (SirT1), and parkin. In MPP+-treated primary cortical neurons, linalool upregulated protein expression of SirT1, γ-Aminobutyric acid type A-α1 (GABAA-α1), and γ-Aminobutyric acid type B (GABAB). In PD-like mice, linalool attenuated the loss of dopamine neurons in SNpc. Linalool improved the motor and nonmotor behavioral deficits and muscle strength of PD-like mice. These findings suggest that linalool potentially protects dopaminergic neurons and improves the impairment symptoms of PD.