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1.
Life Sci ; : 120317, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35026214

RESUMO

AIMS: Angelol-A (Ang-A), a kind of coumarins, is isolated from the roots of Angelica pubescens f. biserrata. However, AA exerts antitumor effects and molecular mechanism on cervical cancer cells is unknown. MAIN METHODS: Cell viability was determined using the MTT assay, and the cell cycle phase was assessed by PI staining with flow cytometry. Ang-A-treated cells with/without Antago-miR-29a-3p (miR-29a-3p inhibitor) or U0126 (MEK inhibitor) were assessed for the expression of miR-29a-3p, in vitro migration/invasion, and angiogenesis using qRT-PCR, a chemotaxis assay, and tube formation assay, respectively. The expression of mitogen-activated protein kinases/MMP2/MMP9/VEGFA was determined by western blot analysis with applicable antibodies. KEY FINDINGS: Ang-A significantly inhibited MMP2 and VEGFA expression, cell migration, and invasive motility in human cervical cancer cells. Conditioned medium inhibited tube formation in HUVECs. Ang-A principally inhibited invasive motility and angiogenesis by upregulating the expression of miR-29a-3p that targets the VEGFA-3' UTR. The role of miR-29a-3p was confirmed using Antago-miR-29a-3p, which reversed the Ang-A-inhibited expression of MMP2 and VEGFA, invasive motility, and angiogenesis in human cervical cancer cells. The ERK pathway was implicated in mediating the metastatic and angiogenic action of Ang-A. Combined treatment with Ang-A treated and U0126 exerted a synergistic inhibitory effect on the expression of MMP2 and VEGFA and the metastatic and angiogenic properties of human cervical cancer cells. SIGNIFICANCE: These findings are the first to indicate that in human cervical cancer cells, Ang-A exerts anti-metastatic and anti-angiogenic effects via targeting the miR-29a-3p/MMP2/VEGFA axis, mediated through the ERK pathway.

2.
Cancers (Basel) ; 14(1)2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-35008389

RESUMO

In the past decade, patients with nasopharyngeal cancer (NPC) have been deemed candidates for proton radiotherapy, due to the large and comprehensive target volumes and the necessity for the retention of the surrounding healthy tissues. In this study, we aimed to compare the incidence and severity of post-irradiation sinusitis by detecting sinus mucosa diseases (SMDs) via the magnetic resonance imaging (MRI) of patients with NPC after intensity-modulated proton therapy (IMPT) and volume-modulated arc therapy (VMAT). A total of 53 patients in the IMPT group and 54 patients in the VMAT group were enrolled in this study. There were significantly lower endoscopic scores and Lund-Mackay staging scores determined from MRI scans in the IMPT group during different follow-up periods. For the most vulnerable sinuses, the incidence and severity of SMD were the highest during the third post-radiotherapy month in both groups. These decreased steadily, and there was no significant increase in the incidence and severity of SMD during the second post-radiotherapy year in the IMPT group. Our data show that NPC patients with IMPT have a significantly lower incidence and decreased severity of SMD than those with VMAT. A better and faster recovery of sinonasal function after radiotherapy in the IMPT group was also observed.

3.
Pharmacol Res ; : 106059, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34998973

RESUMO

Skp1-Cul1-F-box protein (SCF) ubiquitin E3 ligases play important roles in cancer development and serve as a promising therapeutic target in cancer therapy. Brusatol (Bru), a known Nrf2 inhibitor, holds promise for treating a wide range of tumors; however, the direct targets of Bru and its anticancer mode of action remain unclear. In our study, 793 Bru-binding candidate proteins were identified by using a Biotin-Brusatol conjugate (Bio-Bru) followed by streptavidin-affinity pull down-based mass spectrometry. We found that Bru can directly bind to Skp1 and disrupt the interactions of Skp1 with the F-box protein Skp2, leading to the inhibition of the Skp2-SCF E3 ligase. Bru inhibited both proliferation and migration via promoting the accumulation of the substrates p27 and E-cadherin; Skp1 overexpression attenuated while Skp1 knockdown enhanced these effects of Bru in non-small cell lung cancer (NSCLC) cells. Moreover, Bru binding to Skp1 also inhibited the ß-TRCP-SCF E3 ligase. In both subcutaneous and orthotopic NSCLC xenografts, Bru significantly inhibited the growth and metastasis of NSCLC through targeting SCF complex and upregulating p27 and E-cadherin protein levels. These data demonstrate that Bru is a Skp1-targeting agent that may have therapeutic potentials in lung cancer.

4.
J Cereb Blood Flow Metab ; : 271678X211071018, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34994242

RESUMO

Patients with obstructive sleep apnea (OSA) are at elevated risk of developing systemic vascular disease and cognitive dysfunction. Here, cerebral oxygen metabolism was assessed in patients with OSA by means of a magnetic resonance-based method involving simultaneous measurements of cerebral blood flow rate and venous oxygen saturation in the superior sagittal sinus for a period of 10 minutes at an effective temporal resolution of 1.3 seconds before, during, and after repeated 24-second breath-holds mimicking spontaneous apneas, yielding, along with pulse oximetry-derived arterial saturation, whole-brain CMRO2 via Fick's Principle. Enrolled subjects were classified based on their apnea-hypopnea indices into OSA (N = 31) and non-sleep apnea reference subjects (NSA = 21), and further compared with young healthy subjects (YH, N = 10). OSA and NSA subjects were matched for age and body mass index. CMRO2 was lower in OSA than in the YH group during normal breathing (105.6 ± 14.1 versus 123.7 ± 22.8 µmol O2/min/100g, P = 0.01). Further, the fractional change in CMRO2 in response to a breath-hold challenge was larger in OSA than in the YH group (15.2 ± 9.2 versus 8.5 ± 3.4%, P = 0.04). However, there was no significant difference in CMRO2 between OSA and NSA subjects. The data suggest altered brain oxygen metabolism in OSA and possibly in NSA as well.

5.
BMC Health Serv Res ; 22(1): 24, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983501

RESUMO

BACKGROUND: Mobile health applications (mHealth apps) have created innovative service channels for patients with chronic diseases. These innovative service channels require physicians to actively use mHealth apps. However, few studies investigate physicians' participation in mHealth apps. OBJECTIVE: This study aims to empirically explore factors affecting physicians' usage behaviors of mHealth apps. Based on the extended Unified Theory of Acceptance and Use of Technology (UTAUT2) and mHealth apps features, we propose a research model including altruism, cognitive trust, and online ratings. METHODS: We collected data from physicians who have used mHealth apps and conducted a factor analysis to verify the convergence and discriminative effects. We used a hierarchical regression method to test the path coefficients and statistical significance of our research model. In addition, we adopted bootstrapping approach and further analyzed the mediating effects of behavioral intention between all antecedent variables and physicians' usage behavior. Finally, we conducted three robustness analyses to test the validity of results and tested the constructs to verify the common method bias. RESULTS: Our results support the effects of performance expectancy, effort expectancy, social influence, and altruism on the behavioral intentions of physicians using mHealth apps. Moreover, facilitating conditions and habits positively affect physicians using mHealth apps through the mediating effort of behavioral intention. Physicians' cognitive trust and online rating have significant effects on their usage behaviors through the mediating efforts of behavioral intention. CONCLUSIONS: This study contributes to the existing literature on UTAUT2 extension of physicians' acceptance of mHealth apps by adding altruism, cognitive trust, and online ratings. The results of this study provide a novel perspective in understanding the factors affecting physicians' usage behaviors on mHealth apps in China and provide such apps' managers with an insight into the promotion of physicians' active acceptance and usage behaviors.


Assuntos
Aplicativos Móveis , Médicos , Telemedicina , Pesquisa Empírica , Humanos , Intenção
6.
Bioresour Technol ; 343: 126116, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34653622

RESUMO

A heterotrophic nitrification- aerobic denitrification (HNAD) bacterium, Acinetobacter junii ZHG-1, was isolated, meanwhile, the optimal conditions for the strain were evaluated, moreover, the influence mechanism of the C/N ratio on the HNAD process was investigated from the perspective of electron transport and energy level. The increasing of C/N ratio enhanced the reduced/oxidized nicotinamide adenine dinucleotide (NADH/NAD+) ratio, NADH concentration, electron transport system activity (ETSA), ATP content, as well as enzymes activities, consequently, the HNAD performance of the strain can be improved, however, when the C/N ratio was higher than 30, the activities of enzymes relating to the HNAD process and the ETSA had reached the maximum, which might limit the further improvement of the nitrogen removal with the increasing of C/N ratio. As the interaction between different biochemical reactions in HNAD process, more efforts should be devoted to the influent mechanism of different environmental factors on the HNAD process.


Assuntos
Desnitrificação , Nitrificação , Acinetobacter , Aerobiose , Processos Heterotróficos , Nitritos , Nitrogênio
7.
Hear Res ; 414: 108411, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34929535

RESUMO

Healthy aging may be associated with neural degeneration in the cochlea even before clinical hearing loss emerges. Reduction in frequency-following responses (FFRs) to tonal carriers in older clinically normal-hearing listeners has previously been reported, and has been argued to reflect an age-dependent decline in temporal processing in the central auditory system. Alternatively, age-dependent loss of auditory nerve fibers (ANFs) may have little effect on audiometric sensitivity and yet compromise the precision of neural phase-locking relying on joint activity across populations of fibers. This peripheral loss may, in turn, contribute to reduced neural synchrony in the brainstem as reflected in the FFR. Here, we combined human electrophysiology and auditory nerve (AN) modeling to investigate whether age-related changes in the FFR would be consistent with peripheral neural degeneration. FFRs elicited by pure tones and frequency sweeps at carrier frequencies between 200 and 1200 Hz were obtained in older (ages 48-76) and younger (ages 20-30) listeners, both groups having clinically normal audiometric thresholds up to 6 kHz. The same stimuli were presented to a computational model of the AN in which age-related loss of hair cells or ANFs was modelled using human histopathological data. In the older human listeners, the measured FFRs to both sweeps and pure tones were found to be reduced across the carrier frequencies examined. These FFR reductions were consistent with model simulations of age-related ANF loss. In model simulations, the phase-locked response produced by the population of remaining fibers decreased proportionally with increasing loss of the ANFs. Basal-turn loss of inner hair cells also reduced synchronous activity at lower frequencies, albeit to a lesser degree. Model simulations of age-related threshold elevation further indicated that outer hair cell dysfunction had no negative effect on phase-locked AN responses. These results are consistent with a peripheral source of the FFR reductions observed in older normal-hearing listeners, and indicate that FFRs at lower carrier frequencies may potentially be a sensitive marker of peripheral neural degeneration.

8.
Biol Psychiatry ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34865853

RESUMO

BACKGROUND: ADNP is essential for embryonic development. As such, de novo ADNP mutations lead to an intractable autism/intellectual disability syndrome requiring investigation. METHODS: Mimicking humans, CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 editing produced mice carrying heterozygous Adnp p.Tyr718∗ (Tyr), a paralog of the most common ADNP syndrome mutation. Phenotypic rescue was validated by treatment with the microtubule/autophagy-protective ADNP fragment NAPVSIPQ (NAP). RESULTS: RNA sequencing of spleens, representing a peripheral biomarker source, revealed Tyr-specific sex differences (e.g., cell cycle), accentuated in females (with significant effects on antigen processing and cellular senescence) and corrected by NAP. Differentially expressed, NAP-correctable transcripts, including the autophagy and microbiome resilience-linked FOXO3, were also deregulated in human patient-derived ADNP-mutated lymphoblastoid cells. There were also Tyr sex-specific microbiota signatures. Phenotypically, Tyr mice, similar to patients with ADNP syndrome, exhibited delayed development coupled with sex-dependent gait defects. Speech acquisition delays paralleled sex-specific mouse syntax abnormalities. Anatomically, dendritic spine densities/morphologies were decreased with NAP amelioration. These findings were replicated in the Adnp+/- mouse, including Foxo3 deregulation, required for dendritic spine formation. Grooming duration and nociception threshold (autistic traits) were significantly affected only in males. Early-onset tauopathy was accentuated in males (hippocampus and visual cortex), mimicking humans, and was paralleled by impaired visual evoked potentials and correction by acute NAP treatment. CONCLUSIONS: Tyr mice model ADNP syndrome pathology. The newly discovered ADNP/NAP target FOXO3 controls the autophagy initiator LC3 (microtubule-associated protein 1 light chain 3), with known ADNP binding to LC3 augmented by NAP, protecting against tauopathy. NAP amelioration attests to specificity, with potential for drug development targeting accessible biomarkers.

9.
Front Aging Neurosci ; 13: 741168, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34867274

RESUMO

Objective: Ischemic stroke is an important cause of death and disability worldwide. Early reperfusion by thrombolysis or thrombectomy has improved the outcome of acute ischemic stroke. However, the therapeutic window for reperfusion therapy is narrow, and adjuvant therapy for neuroprotection is demanded. Electrical stimulation (ES) has been reported to be neuroprotective in many neurological diseases. In this study, the neuroprotective effect of early somatosensory cortical ES in the acute stage of ischemia/reperfusion injury was evaluated. Methods: In this study, the rat model of transient middle cerebral artery occlusion was used to explore the neuroprotective effect and underlying mechanisms of direct primary somatosensory (S1) cortex ES with an electric current of 20 Hz, 2 ms biphasic pulse, 100 µA for 30 min, starting at 30 min after reperfusion. Results: These results showed that S1 cortical ES after reperfusion decreased infarction volume and improved functional outcome. The number of activated microglia, astrocytes, and cleaved caspase-3 positive neurons after ischemia/reperfusion injury were reduced, demonstrating that S1 cortical ES alleviates inflammation and apoptosis. Brain-derived neurotrophic factor (BDNF) and phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway were upregulated in the penumbra area, suggesting that BDNF/TrkB signals and their downstream PI3K/Akt signaling pathway play roles in ES-related neuroprotection. Conclusion: This study demonstrates that somatosensory cortical ES soon after reperfusion can attenuate ischemia/reperfusion injury and is a promising adjuvant therapy for thrombolytic treatment after acute ischemic stroke. Advanced techniques and devices for high-definition transcranial direct current stimulation still deserve further development in this regard.

10.
Front Med (Lausanne) ; 8: 713535, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869412

RESUMO

Background: Although the self-assessment tools for predicting osteoporosis are convenient for clinicians, they are not commonly used among men. We developed the Male Osteoporosis Self-Assessment Tool for Taiwan (MOSTAi) to identify the patients at risk of osteoporosis. Methods: All the participants completed a questionnaire on the clinical risk factors for the fracture risk assessment tool. The risk index was calculated by the multivariate regression model through the item reduction method. The receiver operating characteristic (ROC) curve was used to analyze its sensitivity and specificity, and MOSTAi was developed and validated. Results: A total of 2,290 men participated in the bone mineral density (BMD) survey. We chose a model that considered two variables (age and weight). The area under the curve (AUC) of the model was 0.700. The formula for the MOSTAi index is as follows: 0.3 × (weight in kilograms) - 0.1 × (years). We chose 11 as the appropriate cut-off value for the MOSTAi index to identify the subjects at the risk of osteoporosis. Conclusions: The MOSTAi is a simple, intuitive, and country-specific tool that can predict the risk of osteoporosis in Taiwanese men. Due to different demographic characteristics, each region of the world can develop its own model to identify patients with osteoporosis more effectively.

12.
Phys Med Biol ; 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34891142

RESUMO

Breathing motion can displace internal organs by up to several cm; as such, it is a primary factor limiting image quality in medical imaging. Motion can also complicate matters when trying to fuse images from different modalities, acquired at different locations and/or on different days. Currently available devices for monitoring breathing motion often do so indirectly, by detecting changes in the outline of the torso rather than the internal motion itself, and these devices are often fixed to floors, ceilings or walls, and thus cannot accompany patients from one location to another. We have developed small ultrasound-based sensors, referred to as 'organ configuration motion' (OCM) sensors, that attach to the skin and provide rich motion-sensitive information. In the present work we tested the ability of OCM sensors to enable respiratory gating during in vivo PET imaging. A motion phantom involving an FDG solution was assembled, and two cancer patients scheduled for a clinical PET/CT exam were recruited for this study. OCM signals were used to help reconstruct phantom and in vivo data into time series of motion-resolved images. As expected, the motion-resolved images captured the underlying motion. In Patient #1, a single large lesion proved to be mostly stationary through the breathing cycle. However, in Patient #2, several small lesions were mobile during breathing, and our proposed new approach captured their breathing-related displacements. In summary, a relatively inexpensive hardware solution was developed here for respiration monitoring. Because the proposed sensors attach to the skin, as opposed to walls or ceilings, they can accompany patients from one procedure to the next, potentially allowing data gathered in different places and at different times to be combined and compared in ways that account for breathing motion.

13.
Plant Pathol J ; 37(6): 596-606, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34897251

RESUMO

Soil-borne diseases are the major problems in mono cropping. A mixture (designated LTM-m) composed of agricultural wastes and a beneficial microorganism Streptomyces saraceticus SS31 was used as soil amendments to evaluate its efficacy for managing Rhizoctonia solani and root knot nematode (Meloidogyne incognita). In vitro antagonistic assays revealed that SS31 spore suspensions and culture broths effectively suppressed the growth of R. solani, reduced nematode egg hatching, and increased juvenile mortality. Assays using two Petri dishes revealed that LTM-m produced volatile compounds to inhibit the growth of R. solani and cause mortality to the root knot nematode eggs and juveniles. Pot and greenhouse tests showed that application of 0.08% LTM-m could achieve a great reduction of both diseases and significantly increase plant fresh weight. Greenhouse trials revealed that application of LTM-m could change soil properties, including soil pH value, electric conductivity, and soil organic matter. Our results indicate that application of LTM-m bio-organic amendments could effectively manage soil-borne pathogens.

14.
J Pers Med ; 11(12)2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34945724

RESUMO

Flow-mediated dilation (FMD) is used to noninvasively assess the health of blood vessels and it has been shown to have a similar predictive ability for cardiovascular disease to traditional risk factors. Skin perfusion pressure (SPP) refers to the blood pressure required to restore capillary or microcirculatory flow after controlled occlusion and the return of flow. SPP has been shown to be an important measurement when making clinical decisions for patients with limb ischemia and to be a predictor of the likelihood of wound healing. Peripheral artery disease is common in hemodialysis (HD) patients. However, little is known about the association between FMD or SPP and peripheral artery disease. The aim of this study was to evaluate the association between FMD and SPP with brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) in HD patients in Taiwan, an area with a high rate of ESRD. This study was conducted at a regional hospital in southern Taiwan. ABI and baPWV values were measured using an ABI automated device. FMD and SPP were measured using ultrasound and a microvasculature blood flow monitor, respectively. Eighty patients were enrolled in this study. Compared to the patients with an ABI ≥ 0.95, those with an ABI < 0.95 had lower SPP of the feet (dorsal and plantar portions, both p < 0.001). After multivariable adjustments, low triglycerides (p = 0.033) and high calcium-phosphate product (p = 0.018) were significantly associated with low FMD. Further, low ABI (p = 0.001) and low baPWV (p = 0.036) were significantly associated with low SPP of dorsal portions. Old age (p = 0.005), low high-density lipoprotein cholesterol (p = 0.016), and low ABI (p = 0.002) were significantly associated with low SPP of plantar portions. This study demonstrated an association between FMD and SPP with peripheral artery disease in HD patients. Patients with low ABI and baPWV had a high risk of low SPP of the feet. However, there was no significant correlation between FMD and ABI or baPWV.

15.
Microorganisms ; 9(12)2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34946096

RESUMO

Probiotics are considered ecofriendly alternatives to antibiotics as immunostimulants against pathogen infections in aquaculture. In the present study, protease-, amylase-, cellulase-, and xylanase-producing Bacillus safensis NPUST1 were isolated from the gut of Nile tilapia, and the beneficial effects of B. safensis NPUST1 on growth, innate immunity, disease resistance and gut microbiota in Nile tilapia were evaluated by feeding tilapia a basal diet or basal diet containing 105 and 106-107 CFU/g for 8 weeks. The results showed that the weight gain, feed efficiency and specific growth rate were significantly increased in tilapia fed a diet containing 106 CFU/g and 107 CFU/g B. safensis NPUST1. Intestinal digestive enzymes, including protease, amylase and lipase, and hepatic mRNA expression of glucose metabolism and growth-related genes, such as GK, G6Pase, GHR and IGF-1, were also significantly increased in the 106 CFU/g and 107 CFU/g B. safensis NPUST1 treated groups. Immune parameters such as phagocytic activity, respiratory burst and superoxide dismutase activity in head kidney leukocytes, serum lysozyme, and the mRNA expression of IL-1ß, IL-8, TNF-α and lysozyme genes were significantly induced in the head kidney and spleen of 106 CFU/g and 107 CFU/g B. safensis NPUST1 treated fish. The cumulative survival rate was significantly increased in fish fed a diet containing 106 CFU/g and 107 CFU/g B. safensis NPUST1 after challenge with Streptococcus iniae. Dietary supplementation with B. safensis NPUST1 improves the gut microbiota of Nile tilapia, which increases the abundance of potential probiotics and reduces the abundance of pathogenic pathogens. The present study is the first to report the use of B. safensis as a potential probiotic in aquaculture, and a diet containing 106 CFU/g B. safensis NPUST1 is adequate for providing beneficial effects on growth performance and health status in tilapia.

16.
Rev Cardiovasc Med ; 22(4): 1541-1546, 2021 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-34957793

RESUMO

Acute ischemic stroke (AIS) continues to be one of the most important medical and social problems in our country. Carotid endarterectomy (CEA) is the standard and effective surgical treatment for AIS prevention in patients with significant carotid artery stenosis. Even though CEA is a safe procedure when performed by an experienced surgeon, it is still associated with risks of operative complications inherent to any surgical intervention. Therefore, immediate postoperative appropriate adjuvant or neurological salvage therapy for AIS patients after CEA is necessary. In this study,we report three patients in our institution who received immediate post-operative interventional therapy for neurological salvage, in the setting of cerebral embolism after CEA.

17.
Biomedicines ; 9(12)2021 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-34944720

RESUMO

A metabolite isolated from fermented soybean, 8-hydroxydaidzein (8-OHD, 7,8,4'-trihydroxyisoflavone, NSC-678112), is widely used in ethnopharmacological research due to its anti-proliferative and anti-inflammatory effects. We reported previously that 8-OHD provoked reactive oxygen species (ROS) overproduction, and induced autophagy, apoptosis, breakpoint cluster region-Abelson murine leukemia viral oncogene (BCR-ABL) degradation, and differentiation in K562 human chronic myeloid leukemia (CML) cells. However, how 8-OHD regulates metabolism, the extracellular matrix during invasion and metastasis, and survival signaling pathways in CML remains largely unexplored. High-throughput technologies have been widely used to discover the therapeutic targets and pathways of drugs. Bioinformatics analysis of 8-OHD-downregulated differentially expressed genes (DEGs) revealed that Janus kinase/signal transducer and activator of transcription (JAK/STAT), matrix metalloproteinases (MMPs), c-Myc, phosphoinositide 3-kinase (PI3K)/AKT, and oxidative phosphorylation (OXPHOS) metabolic pathways were significantly altered by 8-OHD treatment. Western blot analyses validated that 8-OHD significantly downregulated cytosolic JAK2 and the expression and phosphorylation of STAT3 dose- and time-dependently in K562 cells. Zymography and transwell assays also confirmed that K562-secreted MMP9 and invasion activities were dose-dependently inhibited by 8-OHD after 24 h of treatment. RT-qPCR analyses verified that 8-OHD repressed metastasis and OXPHOS-related genes. In combination with DisGeNET, it was found that 8-OHD's downregulation of PI3K/AKT is crucial for controlling CML development. A STRING protein-protein interaction analysis further revealed that AKT and MYC are hub proteins for cancer progression. Western blotting revealed that AKT phosphorylation and nuclear MYC expression were significantly inhibited by 8-OHD. Collectively, this systematic investigation revealed that 8-OHD exerts anti-CML effects by downregulating JAK/STAT, PI3K/AKT, MMP, and OXPHOS pathways, and MYC expression. These results could shed new light on the development of 8-OHD for CML therapy.

18.
Cancers (Basel) ; 13(24)2021 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-34944877

RESUMO

High collagen type XI alpha 1 (COL11A1) levels are associated with tumor progression, chemoresistance, and poor patient survival in several cancer types. MicroRNAs (miRNAs) are dysregulated in multiple cancers, including epithelial ovarian carcinoma (EOC); however, the regulation of COL11A1 by miRNAs in EOC remains unclear. We examined the role of miRNAs in regulating COL11A1 expression. We identified miR-509 and miR-335 as the candidate miRNAs through an online database search. EOC cell treatment with miR-335 mimics abrogated COL11A1 expression and suppressed cell proliferation and invasion, besides increasing the sensitivity of EOC cells to cisplatin. Conversely, treatment with miR-335 inhibitors prompted cell growth/invasiveness and chemoresistance of EOC cells. miR-335 inhibited COL11A1 transcription, thus reducing the invasiveness and chemoresistance of EOC cells via the Ets-1/MMP3 and Akt/c/EBPß/PDK1 axes, respectively. Furthermore, it did not directly regulate PDK1 but increased PDK1 ubiquitination and degradation through COL11A1 inhibition. In vivo findings highlighted significantly decreased miR-335 mRNA expressions in EOC samples. Furthermore, patients with low miR335 levels were susceptible to advanced-stage cancer, poor response to chemotherapy, and early relapse. This study highlighted the importance of miR-335 in downregulating COL11A1-mediated ovarian tumor progression, chemoresistance, and poor survival and suggested its potential application as a therapeutic target.

19.
Sci Rep ; 11(1): 23945, 2021 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-34907314

RESUMO

Maxillary sinus fungal balls (MSFBs) mostly occur in older individuals and demonstrate female predominance. Early diagnosis is important to avoid treatment delays. Intralesional hyperdensity (IH) indicates the presence of heavy metal deposition within fungal hyphae and has been the most specific characteristic of MSFB on computed tomography (CT). For those without IH on CT, the diagnosis of MSFB remains challenging. This study aimed to characterize clinical presentation of MSFB with and without IH and to study factors contributing to MSFB with no IH formation. We retrospectively identified 588 patients with MSFB. The clinical characteristics and CT findings were reviewed. Patients with unilateral MSFB had a mean age of 57.4 years and demonstrated female predominance (64.63%). The female-to-male ratio was highest at 51-60 years (2.02) and rose to 2.60 in MSFB with IH only. Compared to those with IH, MSFB without IH was significantly more common in males (OR = 2.49), in those with diabetes mellitus (DM) (OR = 1.87), adjacent maxillary odontogenic pathology (OR = 1.75). Complete opacification on CT was less common in MSFB without IH (OR = 0.60). Patients with MSFB without IH were more likely to have DM, no female predominance, adjacent maxillary odontogenic pathology, and partial opacification of the sinus, compared to those with IH. These may be helpful in better understanding of the formation of MSFBs without IH, early identification of them and prevention of post-operative recurrence.

20.
Cells ; 10(12)2021 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-34944104

RESUMO

7-Ketocholesterol (7KCh) is a major oxidized cholesterol product abundant in lipoprotein deposits and atherosclerotic plaques. Our previous study has shown that 7KCh accumulates in erythrocytes of heart failure patients, and further investigation centered on how 7KCh may affect metabolism in cardiomyocytes. We applied metabolomics to study the metabolic changes in cardiac cell line HL-1 after treatment with 7KCh. Mevalonic acid (MVA) pathway-derived metabolites, such as farnesyl-pyrophosphate and geranylgeranyl-pyrophosphate, phospholipids, and triacylglycerols levels significantly declined, while the levels of lysophospholipids, such as lysophosphatidylcholines (lysoPCs) and lysophosphatidylethanolamines (lysoPEs), considerably increased in 7KCh-treated cells. Furthermore, the cholesterol content showed no significant change, but the production of cholesteryl esters was enhanced in the treated cells. To explore the possible mechanisms, we applied mRNA-sequencing (mRNA-seq) to study genes differentially expressed in 7KCh-treated cells. The transcriptomic analysis revealed that genes involved in lipid metabolic processes, including MVA biosynthesis and cholesterol transport and esterification, were differentially expressed in treated cells. Integrated analysis of both metabolomic and transcriptomic data suggests that 7KCh induces cholesteryl ester accumulation and reprogramming of lipid metabolism through altered transcription of such genes as sterol O-acyltransferase- and phospholipase A2-encoding genes. The 7KCh-induced reprogramming of lipid metabolism in cardiac cells may be implicated in the pathogenesis of cardiovascular diseases.


Assuntos
Ésteres do Colesterol/metabolismo , Cetocolesteróis/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Miocárdio/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Espaço Intracelular/metabolismo , Metabolismo dos Lipídeos/genética , Metaboloma , Metabolômica , Ácido Mevalônico/metabolismo , Camundongos , Modelos Biológicos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transcrição Genética/efeitos dos fármacos , Triglicerídeos/metabolismo
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