Land-use intensification dominates China's land provisioning services: From the perspective of land system science.

A pressing challenge to global sustainability is meeting the escalating needs of a growing population while safeguarding land resources from degradation. In recent decades, China's rapid growth, expanding population, urban sprawl, and diminishing high-quality farmland have presented a compelling case suitable for exploring solutions and challenges related to this critical issue. Therefore, there is an urgent need for comprehensive and detailed information regarding land systems. Here, we developed the first fine-scale dataset of the China Land System at a spatial resolution of 1 km, covering the period from 2000 to 2015. By leveraging this comprehensive land information, we identified five primary types of land systems and their respective subsystems, thereby delineating distinct patterns of human-environmental interaction. Land system dynamics followed diverse developmental trajectories characterized by incremental shifts toward more functionally centralized systems. Land use intensification played a significant role in increasing the population capacity and food production in China, contributing nearly 93.94% and 84.99%, respectively. In contrast, land cover changes accounted for only 4.69% and 11.43%, respectively. These findings underscore the tendency of previous studies to overestimate the impact of land cover change and underestimate the influence of land use intensification in meeting the growing demands of land-based production. This study emphasizes the importance of transcending traditional land cover-based approaches and integrating land systems into land representation and global land change scenario simulations to promote sustainability.

HuR-positive stress granules: Potential targets for age-related osteoporosis.

Aging impairs osteoblast function and bone turnover, resulting in age-related bone degeneration. Stress granules (SGs) are membrane-less organelles that assemble in response to stress via the recruitment of RNA-binding proteins (RBPs), and have emerged as a novel mechanism in age-related diseases. Here, we identified HuR as a bone-related RBP that aggregated into SGs and facilitated osteogenesis during aging. HuR-positive SG formation increased during osteoblast differentiation, and HuR overexpression mitigated the reduction in SG formation observed in senescent osteoblasts. Moreover, HuR positively regulated the mRNA stability and expression of its target ß-catenin by binding and recruiting ß-catenin into SGs. As a potential therapeutic target, HuR activator apigenin (API) enhanced its expression and thus aided osteoblasts differentiation. API treatment increased HuR nuclear export, enhanced the recruitment of ß-catenin into HuR-positive SGs, facilitated ß-catenin nuclear translocation, and contributed osteogenesis. Our findings highlight the roles of HuR and its SGs in promoting osteogenesis during skeletal aging and lay the groundwork for novel therapeutic strategies against age-related skeletal disorders.

Systemic bevacizumab for treatment of recurrent respiratory papillomatosis.

OBJECTIVES: To characterize treatment response of recurrent respiratory papillomatosis (RRP) including adult-onset RRP (AORRP) and juvenile-onset RRP (JORRP) to systemic bevacizumab (bev), and share our treatment regimen experience. METHODS: Patients were enrolled in bev treatment based on a pathologically confirmed diagnosis of squamous papilloma. According to lesion characteristics and medical history, systemic bev was used as preoperative adjuvant therapy, postoperative adjuvant therapy, or primary therapy. The assessment of treatment response relied on the morphological changes of lesions. Vocalization and voice-related quality of life were evaluated using the voice handicap index-30 (VHI-30) for adults and the pediatric VHI (pVHI) for children. Adverse effect was monitored through patient self-reported symptoms and regular follow-ups. RESULTS: This study included 24 patients, comprising nine AORRP and 15 JORRP cases. In AORRP, all patients (100%) exhibited various degrees of response to systemic bev, with 5 (55.56%) achieving complete response (CR). Among JORRP patients, 14 (93.33%) showed a response to systemic bev, with 8 (53.33%) achieving CR and currently being followed up. No instances of aggravation were observed during systemic bev treatment. A total of 21 patients (21/24, 87.50%) reported voice improvement, accompanied by reduced VHI-30 or pVHI scores across all aspects, including total, functional, physical, and emotional dimensions. No grade 3 or higher adverse events occurred. The most common adverse events were grade 1 gum bleeding (n = 4, 16.67%) and grade 1 proteinuria (n = 4, 16.67%). CONCLUSIONS: Systemic bev can be used as a powerful therapy for both AORRP and JORRP. The findings provide a reference to the systemic bev treatment for RRP.

Office-based 532-nm KTP laser as a therapeutic modality for recurrent laryngeal papillomatosis: efficacy and relative factors.

This study aims to investigate the efficacy of office-based potassium-titanyl-phosphate (KTP) 532-nm laser in the management of recurrent laryngeal papillomatosis (RLP) following other treatments. A retrospective assessment was performed on 55 patients in 259 cases of RLP between 2012 and 2019. Derkay scores were obtained for all patients who underwent 532-nm KTP laser procedure (6 W of power with a continuous output mode) prior to treatment and after treatment. Analysis of parameters is based on the distribution characteristics of data. An ordinal logistic regression was also performed. Patients received a median of 3 (range 1-24) office-based KTP laser treatments. Among them, 96.36% (53 patients) were previously on cold steel equipment, CO2 laser, or microdebrider treatment under general anesthesia, and all previous treatments on them had failed. One patient progressed to invasive cancer, so he was excluded from the following analyses. After final KTP treatment, 36 patients (66.67%) received complete resolution with follow-up time ranging from 12.9 to 80.53 months (median 55.54 months). Results of subjective voice-quality indicators such as VHI-30 and GRBAS all improved greatly at the last follow-up. The initial Derkay scores and treatment intervals were found to be predictive of complete lesion remission. Arytenoid involvement may also correlate with lesion resolution. Serial office-based KTP treatment is an effective option for RLP patients, with ideal disease control and voice quality preservation. KTP laser therapy should be repeated with an interval of 1 month from the beginning of treatment until the lesion has been evaluated and subsided. Non-bulk or scattered laryngeal papilloma is an appropriate indication for KTP laser treatment.

How do RNA binding proteins trigger liquid-liquid phase separation in human health and diseases?

RNA-binding proteins (RBPs) lie at the center of post-transcriptional regulation and protein synthesis, adding complexity to RNA life cycle. RBPs also participate in the formation of membrane-less organelles (MLOs) via undergoing liquid-liquid phase separation (LLPS), which underlies the formation of MLOs in eukaryotic cells. RBPs-triggered LLPS mainly relies on the interaction between their RNA recognition motifs (RRMs) and capped mRNA transcripts and the heterotypic multivalent interactions between their intrinsically disordered regions (IDRs) or prion-like domains (PLDs). In turn, the aggregations of RBPs are also dependent on the process of LLPS. RBPs-driven LLPS is involved in many intracellular processes (regulation of translation, mRNA storage and stabilization and cell signaling) and serves as the heart of cellular physiology and pathology. Thus, it is essential to comprehend the potential roles and investigate the internal mechanism of RPBs-triggered LLPS. In this review, we primarily expound on our current understanding of RBPs and they-triggered LLPS and summarize their physiological and pathological functions. Furthermore, we also summarize the potential roles of RBPs-triggered LLPS as novel therapeutic mechanism for human diseases. This review will help understand the mechanisms underlying LLPS and downstream regulation of RBPs and provide insights into the pathogenesis and therapy of complex diseases.

Liquid-Liquid Phase Separation of Biomacromolecules and Its Roles in Metabolic Diseases.

Liquid-liquid phase separation (LLPS) compartmentalizes and concentrates biomacromolecules into liquid-like condensates, which underlies membraneless organelles (MLOs) formation in eukaryotic cells. With increasing evidence of the LLPS concept and methods, this phenomenon as a novel principle accounts for explaining the precise spatial and temporal regulation of cellular functions. Moreover, the phenomenon that LLPS tends to concentrate proteins is often accompanied by several abnormal signals for human diseases. It is reported that multiple metabolic diseases are strongly associated with the deposition of insoluble proteinaceous aggregating termed amyloids. At present, recent studies have observed the roles of LLPS in several metabolic diseases, including type 2 diabetes mellitus (T2DM), Alzheimer's disease (AD), and metabolic bone diseases (MBDs). This review aims to expound on the current concept and methods of LLPS and summarize its vital roles in T2DM, AD, and MBDs, uncover novel mechanisms of these metabolic diseases, and thus provide powerful potential therapeutic strategies and targets for ameliorating these metabolic diseases.

Combination of carboplatin and photodynamic therapy with 9-hydroxypheophorbide ɑ enhances mitochondrial and endoplasmic reticulum apoptotic effect in AMC-HN-3 laryngeal cancer cells.

BACKGROUND: Previously, we demonstrated that the combined mode of carboplatin (CBDCA) and photodynamic therapy (PDT) based on 9-hydroxypheophorbide (9-HPbD) enhanced cytotoxicity and apoptosis on AMC-HN-3 laryngeal cancer cells. The present study aimed to investigate anti-tumor effect of the combined therapy in vivo and the potential role of reactive oxygen species (ROS) in these enhanced apoptotic pathways initiated by the combined therapy in AMC-HN-3 cells. METHODS: Mitochondrial membrane potential (MMP) and intracellular Ca2+were detected under confocal microscopy. Various apoptotic pathways were detected by western blots. In vivo study with the combined regimen was also performed on AMC-HN-3 cells-xenograft nude mice. RESULTS: In vitro study showed that the combined treatment could decrease the level of MMP, increase intracellular Ca2+ and AIF translocation, and activate the expression of caspase-12. Mechanismly, the augmented apoptotic effect was mediated by ROS. The synergistic antitumor effect was also observed in vivo. CONCLUSIONS: The mechanism of CBDCA and 9-HPbD-PDT combination involves ROS-mediated mitochondrial and endoplasmic reticulum apoptosis pathways. This combination may be a promising treatment strategy for laryngeal cancer.

MiR-138-5p Targets MACF1 to Aggravate Aging-related Bone Loss.

Senile osteoporosis is one of the major health problems in an aging society. Decreased bone formation due to osteoblast dysfunction may be one of the causes of aging-related bone loss. With increasing evidence suggesting that multiple microRNAs (miRNAs) play important roles in osteoblast function, the relationship between miRNAs and senile osteoporosis has become a popular research topic. Previously, we confirmed that mechanoresponsive miR-138-5p negatively regulated bone anabolic action. In this study, the miR-138-5p level was found to be negatively correlated with BMD and osteogenic markers in bone specimens of senile osteoporotic patients by bioinformatic analysis and experimental verification. Furthermore, high miR-138-5p levels aggravated the decrease of aged osteoblast differentiation in vitro and led to worse bone loss in aged osteoblastic miR-138-5p transgenic mice in vivo. We also previously identified that the target of miR-138-5p, microtubule actin cross-linking factor 1 (MACF1), could attenuate senile osteoporosis. Here, miR-138-5p was demonstrated to regulate aged osteoblast differentiation by targeting MACF1. Finally, the therapeutic inhibition of miR-138-5p counteracted the decrease in bone formation and aging-related bone loss in aged mice. Overall, our results highlight the crucial roles and the molecular mechanism of miR-138-5p in aging-related bone loss and may provide a powerful therapeutic target for ameliorating senile osteoporosis.

Use of 532 nm Potassium Titanyl Phosphate Laser on Vocal Fold Scars Under Topical Anesthesia: A Pilot Study.

OBJECTIVE: This pilot study aims to evaluate the efficacy of 532 nm potassium titanyl phosphate (KTP) laser under topical anesthesia in patients with vocal fold scars. METHODS: A series of 18 patients with vocal fold scars of varying degrees were treated. The KTP laser was used under local anesthesia in the outpatient clinic. It was set to deliver 6 W of power using a continuous output mode. Close-to-contact mode was used for laser irradiation, and contact mode was used for ablation and excision of the lesions. Some of the patients received laser scar ablation on both vocal folds; the scarred vocal fold on one side and the hypertrophic vocal fold on the other. Parameters include glottic closure, amplitude, and mucosal wave pattern were measured using laryngeal stroboscopic examination. Aerodynamic and voice evaluations were carried out using maximum phonation time (MPT), jitter, shimmer, Voice Handicap Index questionnaire (VHI-30), and GRBAS scale. RESULTS: In total, 21 surgeries were performed on 18 patients. Glottic closure, amplitude, and mucosal wave pattern showed improvement 2 months postoperatively (P < .05). There was significant improvement in the postoperative scores for VHI-30, VHI-emotional sub-scale, VHI-physical sub-scale, and GRBAS (P < .05). There was no significant difference in the MPT and VHI-functional sub-scale before and after the operation (P > .05). Re-adhesion of the anterior commissure was observed in 2 patients with Type III scars. CONCLUSION: The 532 nm KTP laser is an effective tool for the treatment of vocal fold scars. Further research is required to determine if serial laser applications could improve outcomes for this challenging condition. LEVEL OF EVIDENCE: Level IV.

Comparative Efficacy of the KTP Laser and Cold Steel in Office-Based Surgery for Oropharyngeal Papilloma.

Objective: This study aims to compare the efficacy of the potassium-titanyl-phosphate (KTP) laser and cold steel surgery in treating oropharyngeal papilloma. Methods: Between 2017 and 2020, we enrolled 242 patients with oropharyngeal papilloma who were treated with either the KTP laser (n = 160) or cold steel surgery (n = 82). Patient charts were reviewed for demographic data (age and gender), pathology, anatomical location of lesions, operative duration, pain rating, residual disease, and recurrence. Results: The oropharyngeal papillomas were successfully removed in all patients, except one with a significant pharyngeal reflex. There was no significant difference in the average time for lesion resection between KTP laser and cold steel group (18.11 ± 13.96 s vs 19.43 ± 16.91 s, P > .05). However, all patients who underwent cold steel surgery experienced bleeding during the operation and required postoperative observation (about 20 min), making the total procedure time longer than that of the KTP laser procedure, which did not cause any intraoperative bleeding or require postoperative observation. After KTP laser treatment, the pain rating was .49 ± .98, whereas after cold steel surgery, it was .74 ± 1.12 (P = .058). Twenty-five samples were sent for human papillomavirus (HPV) testing, and one tested positive for both HPV 6 and 11 strains, while another tested positive for HPV 16. No residual disease or recurrence was observed at the treatment sites after a long period of follow-up (M = 15.35 ± 10.79 mo; range = 6-39 mo). Conclusion: The KTP laser provided a better hemostasis effect and a good surgical field of vision during the operation, allowing the surgeon to complete the procedure in less time. No significant difference in terms of pain rating, incision recovery, and postoperative recurrence between the KTP laser treatment and cold steel surgery.

Quyu Shengxin Decoction Alleviates DSS-Induced Ulcerative Colitis in Mice by Suppressing RIP1/RIP3/NLRP3 Signalling.

PURPOSE: To study the therapeutic effect of Quyu (QY) Shengxin (SX) decoction (QYSXD) in mice with dextran sulfate sodium- (DSS-) induced ulcerative colitis and to investigate the effects of QYSXD on the regulation of the receptor-interacting protein kinase 1 (RIP1)/receptor-interacting protein kinase 3 (RIP3)/nucleotide-binding oligomerization domain-like receptor family pyrin domain protein 3 (NLRP3) signaling pathway. METHOD: Thirty-six mice were randomly divided into the following 6 groups: the experimental group (QYSX group), the model group (DSS group), the positive control group (5-aminosalicylic acid (5-ASA) group), the control group, the first component group (QY group), and the second component group (SX group). Each group included 6 mice. Ulcerative colitis (UC) was induced in the mice by providing 3.5% DSS in drinking water. The mice were weighed every day to evaluate the disease activity index (DAI). After 7 days, the mice were sacrificed, and colonic tissues were obtained for colon length measurement. The morphological changes in the colon and the pathological scores of the mice in each group were observed by hematoxylin-eosin (HE) staining. The messenger ribonucleic acid (mRNA) and protein expression levels of RIP1, RIP3, dynamin-related protein 1 (Drp1), NLRP3, cysteinyl aspartate specific proteinase-1 (caspase-1), interleukin (IL)-1ß, and IL-18 in the colon tissues of the mice in each group were detected and compared by real-time quantitative reverse transcription PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). The levels of RIP1, RIP3, NLRP3, IL-1ß, and IL-8 in the colonic mucosa were detected by ELISA. Western blotting was used to compare the protein expression of Drp1, caspase-1, mitochondrial fission protein 1 (FIS1), and mitophagy-associated protein light chain 3a/b (LC3a/b) among groups. The levels of reactive oxygen species (ROS) in the colonic mucosal cells were compared by immunofluorescence. RESULTS: Compared with those in the DSS group, the mice with DSS-induced colitis in the QYSX group exhibited clearly higher body weights (P < 0.05) and DAI scores (P < 0.05). The colon lengths of the mice in the QYSX group were longer than those in the DSS group (P < 0.05), and the pathological score of the QYSX group was lower than that of the DSS group (P < 0.05). The RIP1, RIP3, Drp1, IL-1ß, IL-18, and caspase-1 mRNA levels in the QYSX, 5-ASA, SX, and QY groups were significantly lower than those in the DSS group (P < 0.05), but there were no differences between the QYSX group and the 5-ASA group. The levels of RIP1, RIP3, NLRP3, IL-1ß, and IL-18 in the QYSX group were lower than those in the DSS group (P < 0.01). The levels of Drp1, caspase-1, FIS1, and LC3a/b in the QYSX group and the 5-ASA group were lower than those in the DSS group (P < 0.05). The levels of ROS in the colonic mucosal cells in the QYSX, 5-ASA, and QY groups were lower than those in the DSS group (P < 0.05). CONCLUSION: QYSXD has certain therapeutic effects on DSS-induced colitis in mice and may be as effective as 5-ASA. QY and SX decoctions also have certain effects on colitis; however, these decoctions are not as beneficial as QYSXD. QYSXD may ameliorate colitis by inhibiting the expression of RIP1/RIP3/NLRP3 pathway-related proteins and reversing mitochondrial dysfunction to control inflammation.

Knockdown of CYP1B1 suppresses the behavior of the extravillous trophoblast cell line HTR-8/SVneo under hyperglycemic condition.

Introduction: Trophoblast plays a vital role in the embryonic implantation and function of the placenta. Exposure to a hyperglycemic environment results in the abnormal function of trophoblasts during fetoplacental development, which leads to maternal complications and poor fetal outcomes. However, the precise mechanisms of placental pathology during hyperglycemia remain elusive. We investigated the role of CYP1B1 in the functional behavior of the extravillous trophoblast (EVT) cell line HTR-8/SVneo under hyperglycemic condition.Methods: We determined the expression of CYP1B1 via real-time polymerase chain reaction and Western blot. Specific CYP1B1 inhibitors and small interfering RNA were used to knockdown CYP1B1, whereas an agonist and an adenovirus were used to overexpress CYP1B1. The proliferation, migration, and invasion of the EVT cell line (i.e. HTR-8/SVneo) were assessed via colony formation, 5-ethynyl-2-deoxyuridine, wound healing, and transwell assay.Results: CYP1B1 is highly expressed in placentas from women with gestational diabetes mellitus. The blockage of CYP1B1 inhibits EVT activities induced by hyperglycemia in vitro, including proliferation, migration, and invasion, whereas the exogenous expression of CYP1B1 exhibits the opposite effects.Discussion: Our study may offer a new method for regulating EVT motility under hyperglycemic condition via CYP1B1.

Treatment Outcomes of Arytenoid Dislocation by Closed Reduction: A Multidimensional Evaluation.

OBJECTIVE: This study aimed to investigate the treatment outcomes of arytenoid dislocation by a multidimensional evaluation. METHODS: From April 2010 to May 2018, the records of 57 patients with a history of arytenoid dislocation were reviewed. All the patients were treated with closed reduction under local anesthesia. Arytenoid motion, grade, roughness, breathiness, asthenia, strain, maximum phonation time, self-assessed Voice Handicap Index, and acoustic voice analysis were used to evaluate the clinical outcomes. RESULTS: Following closed reduction, 57 patients were divided into "recovered" (n = 24), "improved" (n = 15), and "ineffective" (n = 18) groups. There were no major complications resulting from surgical intervention. CONCLUSION: Closed reduction under local anesthesia continues to be an effective and well-tolerated method for treating arytenoid dislocation. The trichotomy of the treatment results of arytenoid dislocation by a multidimensional evaluation may be more accurate to evaluate the results of arytenoid dislocation.

A 532-nm KTP Laser for Vocal Fold Polyps: Efficacy and Relative Factors.

OBJECTIVE: We retrospectively analyzed the laryngoscopy results and voice outcomes of patients with vocal polyps who received potassium titanyl phosphate (KTP) laser treatments in a clinician's office, in order to establish the effectiveness and relative factors affecting the efficacy of this treatment. MATERIAL AND METHODS: We enrolled 25 patients with vocal polyps who had undergone KTP laser treatment in the Department of Otorhinolaryngology at our hospital between July 2017 and November 2019. Pre- and postoperative evaluations were measured using laryngovideostroboscopy (LVS), the Voice Handicap Index questionnaire (VHI-30), the GRBAS scale (G hoarseness, R roughness, B breathiness, A asthenia, S strain), and objective acoustic parameters. The reduction rate of lesions was calculated and relative factors affecting efficacy (size, side, location, the position of lesions, type, gender, and occupation) were tested. RESULTS: Areas of lesions decreased from 101.95 ± 70.16 before surgery to 30.49 ± 35.80 after surgery (Z = 5.234, P < .001). The LVS data showed that the postoperative proportions of normal to mild conditions were the same or higher than the preoperative data in 3 instances: glottal closure (100% vs 100%), amplitude (90.91% vs 63.64%), and mucosal wave (81.82% vs 54.55%). A significant improvement was observed in VHI-30 scores, GRBAS scores, and acoustic parameters (P < .05). The size of lesions had an effect on the GRBAS scores (P < .001) but not on VHI-30 scores and objective acoustic parameters (P > .05). Other factors we tested did not affect voice outcomes. CONCLUSION: Potassium titanyl phosphate laser treatment can effectively reduce the lesion area of vocal polyps and improve the voice quality. The presence of small lesions seems to predict good subjective assessments of voice quality, but it remains to be seen whether this correlates with true voice quality.

Rate and Determinants of Recurrence at 1 Year and 5 Years After Stroke in a Low-Income Population in Rural China.

Recurrent stroke is becoming an increasingly important public health issue owing to the increased risk of disability and death. However, population-based studies investigating the rate of recurrent stroke in China are rare. We explored the rate and determinants of recurrent stroke within 1 and 5 years after the initial stroke in a rural population in China. Data for stroke events were obtained from the Tianjin Brain Study, conducted between 1992 and 2016. The age-standardized rates of recurrent stroke within the first year and the first 5 years after the initial stroke were calculated for this period. Determinants of recurrent stroke were assessed using Cox regression analyses. The overall age-standardized rate of recurrent stroke within 1 year was 5.7% (men, 6.9%; women, 4.6%); within 5 years, the overall recurrent stroke rate was 22.5% (men, 24.0%; women, 20.2%). The recurrence rate increased with advancing age and decreased with increased educational attainment. Age ≥65 years and a history of alcohol consumption were independent risk factors for recurrent stroke within 1 year after the incident stroke, after adjusting for age, sex, education, hypertension, diabetes, smoking, and alcohol consumption. However, the risk of recurrent stroke within 5 years after the incident stroke was positively associated with male sex, age ≥65 years, a lower level of education, known diabetes, and alcohol consumption, after adjusting for the previously indicated covariates. These findings suggest a crucial need to address risk factor management among stroke patients to reduce the burden of stroke, especially among low-income populations. Furthermore, a multicenter, large sample, nationwide study is urgently needed.

A Sharp Decline in Burden of Stroke in Rural China During COVID-19 Pandemic.

This study aimed to explore trends in the burden from stroke associated with home quarantine during the COVID-19 pandemic. Patients with a first-ever stroke registered between January 1 and April 20 from 2010 to 2020 were included in this study. We compared the incidence and the rates of mortality, hospitalization, and diagnosis by neuroimaging for first-ever stroke among a low-income population in rural China during the study periods. Overall, 377 first-ever stroke patients were analyzed in this study period; men accounted for 59.2%. Compared with 2019, the incidence of first-ever stroke was 73.5% lower in 2020 (P < 0.001). The incidence of first-ever stroke was lower by 64.18% in 2020 than in the previous 5 years (P = 0.002) and by 65.42% in 2020 than in the previous 10 years (P = 0.001). Mortality from first-ever stroke in 2020 was not significantly different from that in 2019, but it was noticeably lower than that for the previous 5 and 10 years. However, rates of hospitalization and diagnosis by neuroimaging remained stable across the study period. These findings suggest that the home quarantine helped reduce outdoor activities at low temperatures, restrict gatherings, reduce alcoholism and high-fat diet, and lower pollution caused by factories. These changes were advantageous for helping high-risk groups to reduce the burden of stroke.

Andrographolide sensitizes Hep-2 human laryngeal cancer cells to carboplatin-induced apoptosis by increasing reactive oxygen species levels.

Andrographolide is a natural diterpenoid from Andrographis paniculata that has been proposed as an anticancer agent as well as a chemosensitizer for use in combination with anticancer drugs. Carboplatin is the first-line chemotherapeutic agent for advanced laryngeal carcinoma. However, the clinical efficacy of carboplatin is limited by drug resistance and side effects. The aim of this study was to investigate whether andrographolide has a synergistic antitumor effect with carboplatin on human laryngeal cancer cells. Hep-2 cells were exposed to andrographolide with or without carboplatin. The effects of indicated therapies were examined using the Cell Counting Kit-8 assay, the colony-forming assay, the Hoechst 33342/PI double staining, and flow cytometry analysis. The molecular mechanism was assessed by reactive oxygen species (ROS) detection and western blot. At the sublethal concentration, andrographolide increased carboplatin sensitivity of Hep-2 cells by increasing carboplatin-induced apoptosis and inhibiting cell viability. Moreover, we found that andrographolide sensitized carboplatin mainly through the induction of ROS generation and apoptotic signaling. Taken together, these results indicate that andrographolide, along with carboplatin, synergistically inhibited cell proliferation and induced mitochondrial apoptosis of Hep-2 cells by increasing the intracellular ROS, regulating the mitogen-activated protein kinase and phosphatidylinositol 3-kinase (PI3K/AKT) pathways, altering the BCL2/BAX ratio, and ultimately activating the cleavage of Caspase-3 and PARP. These results suggest that andrographolide sensitizes human laryngeal cancer cells to carboplatin-induced apoptosis by increasing ROS levels.

Effects of autophagy on synaptic-plasticity-related protein expression in the hippocampus CA1 of a rat model of vascular dementia.

This study aimed to explore the relationship between autophagy and synaptic plasticity in the pathogenesis of vascular dementia (VD). The autophagy inhibitor 3-methyladenine (3-MA) and the autophagy agonist rapamycin (Rap) were injected into the lateral ventricles of rats, and a rat VD model was established using a modified four-vessel occlusion method. The expression of LC3-II, synaptophysin (Syn), and postsynaptic density protein 95 (PSD-95) in the CA1 area of the rat hippocampus were detected using western blotting. Decreased Syn and PSD-95 expression in the VD group was accompanied by an increased LC3-II/LC3-I ratio. The expression of Syn and PSD-95 increased after 3-MA application, but decreased following Rap application. The LC3-II/LC3-I ratio was negatively correlated with Syn and PSD-95 expression. These findings suggest that autophagy may regulate synaptic plasticity in the hippocampus in a VD model of rats. Inhibition of autophagy is beneficial to the remodeling of synapses in the hippocampal CA1 area of the VD rat model, and this may provide a theoretical basis for the treatment and prevention of VD.

Oxidative stress induced by carboplatin promotes apoptosis and inhibits migration of HN-3 cells.

Laryngeal squamous cell carcinoma (LSCC) is currently a serious public health problem in China; thus, it is urgent to identify effective treatment strategies for this disease. Previous studies demonstrated that reactive oxygen species (ROS) serve important roles in the apoptosis of LSCC cells. It has also been indicated that carboplatin (CBDCA), a second-generation platinum compound with broad antineoplastic properties, is able to induce oxidative stress to produce ROS, which in turn promotes apoptosis. Thus, the present study investigated if CBDCA is cytotoxic in LSCC cells due to the oxidative stress caused by ROS. Therefore, an MTT assay was performed to determine the cell viability of HN-3 LSCC cells following treatment with different doses of CBDCA. Subsequently, the expression levels of ROS and the rate of apoptosis/necrosis were evaluated in the cells. Following this, the HN-3 cells were co-treated with CBDCA and glutathione (GSH) or H2O2, followed by an MTT assay, a cell migration assay and western blot analysis. The results demonstrated that CBDCA reduced the viability of HN-3 cells in a time- and dose-dependent manner and promoted the production of ROS and apoptosis at certain doses. Additionally, the combination treatment of CBDCA and H2O2 enhanced the inhibitory effects of CBDCA on cell viability and migration ability, and promoted apoptosis in HN-3 cells; whereas the combined treatment of CBDCA and GSH exerted opposite effects. The results of the present study demonstrated that CBDCA promotes the apoptosis of HN-3 cells through accumulation of ROS, which may provide a novel treatment strategy for treating LSCC.