Systemic and cerebrospinal fluid biomarkers for tuberculous meningitis identification and treatment monitoring.

IMPORTANCE: Tuberculous meningitis is a life-threatening infection with high mortality and disability rates. Current diagnostic methods using cerebrospinal fluid (CSF) samples have limited sensitivity and lack predictive biomarkers for evaluating prognosis. This study's findings reveal excessive activation of the immune response during tuberculous meningitis (TBM) infection. Notably, a strong negative correlation was observed between CSF levels of monokine induced by interferon-γ (MIG) and the CSF/blood glucose ratio in TBM patients. MIG also exhibited the highest area under the curve with high sensitivity and specificity. This study suggests that MIG may serve as a novel biomarker for differentiating TBM infection in CSF or serum, potentially leading to improved diagnostic accuracy and better patient outcomes.

[Enteral nutrition support for lysinuric protein intolerance: a case report and literature review]. / èµ–æ°¨é ¸å°¿æ€§è›‹ç™½è€å—ä¸è‰¯æ‚£å„¿çš„è‚ å† è¥å »æ”¯æŒ1ä¾‹å¹¶æ–‡çŒ®å¤ä¹ .

OBJECTIVES: To summarize the clinical characteristics and nutrition therapy for children with lysinuric protein intolerance (LPI). METHODS: The clinical manifestations, laboratory test results and enteral nutrition treatment in a girl with LPI diagnosed in Xiangya Hospital, Central South University were retrospective analyzed. Additionally, the data of the children with LPI reported in China and overseas were reviewed. RESULTS: A case of 4-year-old girl was presented, who exhibited significant gastrointestinal symptoms, such as chronic abdominal distension, prolonged diarrhea, recurrent pneumonia, and limited growth. She had a poor response to anti-infection treatment. After receiving enteral nutrition therapy, she did not experience any gastrointestinal discomfort, and there were improvements in the levels of hemoglobin, albumin, and blood ammonia. Unfortunately, due to serious illness, she declined further treatment and later passed away. A total of 92 cases of pediatric patients with LPI have been reported to date, including one case reported in this study. Most children with LPI experienced disease onset after weaning or introduction of complementary foods, presenting with severe digestive system symptoms, malnutrition, and growth retardation. It is noteworthy that only 50% (46/92) of these cases received nutritional therapy, which effectively improved their nutritional status. Among the 92 children, 8 (9%) died, and long-term follow-up data were lacking in other reports. CONCLUSIONS: LPI often involves the digestive system and may result in growth restriction with a poor prognosis. Nutritional therapy plays a crucial role in the comprehensive treatment of LPI.

Single-cell characterization of self-renewing primary trophoblast organoids as modeling of EVT differentiation and interactions with decidual natural killer cells.

BACKGROUND: Extravillous trophoblast cell (EVT) differentiation and its communication with maternal decidua especially the leading immune cell type natural killer (NK) cell are critical events for placentation. However, appropriate in vitro modelling system and regulatory programs of these two events are still lacking. Recent trophoblast organoid (TO) has advanced the molecular and mechanistic research in placentation. Here, we firstly generated the self-renewing TO from human placental villous and differentiated it into EVTs (EVT-TO) for investigating the differentiation events. We then co-cultured EVT-TO with freshly isolated decidual NKs for further study of cell communication. TO modelling of EVT differentiation as well as EVT interaction with dNK might cast new aspect for placentation research. RESULTS: Single-cell RNA sequencing (scRNA-seq) was applied for comprehensive characterization and molecular exploration of TOs modelling of EVT differentiation and interaction with dNKs. Multiple distinct trophoblast states and dNK subpopulations were identified, representing CTB, STB, EVT, dNK1/2/3 and dNKp. Lineage trajectory and Seurat mapping analysis identified the close resemblance of TO and EVT-TO with the human placenta characteristic. Transcription factors regulatory network analysis revealed the cell-type specific essential TFs for controlling EVT differentiation. CellphoneDB analysis predicted the ligand-receptor complexes in dNK-EVT-TO co-cultures, which relate to cytokines, immunomodulation and angiogenesis. EVT was known to affect the immune properties of dNK. Our study found out that on the other way around, dNKs could exert effects on EVT causing expression changes which are functionally important. CONCLUSION: Our study documented a single-cell atlas for TO and its applications on EVT differentiation and communications with dNKs, and thus provide methodology and novel research cues for future study of human placentation.

Regulation of short-chain fatty acids in the immune system.

A growing body of research suggests that short-chain fatty acids (SCFAs), metabolites produced by intestinal symbiotic bacteria that ferment dietary fibers (DFs), play a crucial role in the health status of symbiotes. SCFAs act on a variety of cell types to regulate important biological processes, including host metabolism, intestinal function, and immune function. SCFAs also affect the function and fate of immune cells. This finding provides a new concept in immune metabolism and a better understanding of the regulatory role of SCFAs in the immune system, which impacts the prevention and treatment of disease. The mechanism by which SCFAs induce or regulate the immune response is becoming increasingly clear. This review summarizes the different mechanisms through which SCFAs act in cells. According to the latest research, the regulatory role of SCFAs in the innate immune system, including in NLRP3 inflammasomes, receptors of TLR family members, neutrophils, macrophages, natural killer cells, eosinophils, basophils and innate lymphocyte subsets, is emphasized. The regulatory role of SCFAs in the adaptive immune system, including in T-cell subsets, B cells, and plasma cells, is also highlighted. In addition, we discuss the role that SCFAs play in regulating allergic airway inflammation, colitis, and osteoporosis by influencing the immune system. These findings provide evidence for determining treatment options based on metabolic regulation.

Application of a JEG-3 organoid model to study HLA-G function in the trophoblast.

The human placenta is a unique temporary organ with a mysterious immune tolerance. The formation of trophoblast organoids has advanced the study of placental development. HLA-G is uniquely expressed in the extravillous trophoblast (EVT) and has been linked to placental disorders. With older experimental methodologies, the role of HLA-G in trophoblast function beyond immunomodulation is still contested, as is its role during trophoblast differentiation. Organoid models incorporating CRISPR/Cas9 technology were used to examine the role of HLA-G in trophoblast function and differentiation. JEG-3 trophoblast organoids (JEG-3-ORGs) were established that highly expressed trophoblast representative markers and had the capacity to differentiate into EVT. CRISPR/Cas9 based on HLA-G knockout (KO) significantly altered the trophoblast immunomodulatory effect on the cytotoxicity of natural killer cells, as well as the trophoblast regulatory effect on HUVEC angiogenesis, but had no effect on the proliferation and invasion of JEG-3 cells and the formation of TB-ORGs. RNA-sequencing analysis further demonstrated that JEG-3 KO cells followed similar biological pathways as their wild-type counterparts during the formation of TB-ORGs. In addition, neither HLA-G KO nor the exogenous addition of HLA-G protein during EVT differentiation from JEG-3-ORGs altered the temporal expression of the known EVT marker genes. Based on the JEG-3 KO (disruption of exons 2 and 3) cell line and the TB-ORGs model, it was determined that HLA-G has a negligible effect on trophoblast invasion and differentiation. Despite this, JEG-3-ORG remains a valuable model for studying trophoblast differentiation.

Comparison of the total and hidden blood loss in patients undergoing single-level open and unilateral biportal endoscopic transforaminal lumbar interbody fusion: a retrospective case control study.

PURPOSE: This study aimed to compare total blood loss (TBL) and hidden blood loss (HBL) in patients undergoing single-level open transforaminal lumbar interbody fusion (O-TLIF) and unilateral biportal endoscopic transforaminal lumbar interbody fusion (ULIF). METHODS: A total of 53 patients who underwent ULIF and 53 patients who underwent O-TLIF from March 2020 to July 2022 were retrospectively reviewed. The Nadler's formula was employed to estimate the patient's blood volume (PBV), Gross's formula to estimate TBL, and Sehat's formula to estimate HBL. The obtained data were then analyzed with independent t test, chi-squared test, and analysis of covariance. RESULTS: TBL and measured blood loss (MBL) in ULIF group (326.86 ± 223.45 ml, 99.00 ± 72.81 ml) was significantly lower than O-TLIF group (427.97 ± 280.52 ml, 270.66 ± 102.34 ml). Nevertheless, the HBL in ULIF group was higher than that in O-TLIF group (227.86 ± 221.75 ml vs 157.31 ± 268.08 ml), however this was not statistically significant (p = 0.143). The HBL was 69.71 ± 23.72% of TBL in ULIF group and 36.76 ± 18.79% of TBL in O-TLIF group. Patients in ULIF group had lower TBL and MBL, shorter duration of drainage, lower postoperative anemia, and shorter postoperative hospital stay compared to those in O-TLIF group. CONCLUSIONS: Perioperative HBL should not be neglected in patients undergoing ULIF or O-TILF, as it accounts for a large percentage of TBL in both groups. ULIF is associated with lower TBL and MBL, postoperative anemia, shorter postoperative hospital stays compared with O-TLIF.

MIR497HG-Derived miR-195 and miR-497 Mediate Tamoxifen Resistance via PI3K/AKT Signaling in Breast Cancer.

Tamoxifen is commonly used for the treatment of patients with estrogen receptor-positive (ER+) breast cancer, but the acquired resistance to tamoxifen presents a critical challenge of breast cancer therapeutics. Recently, long noncoding RNA MIR497HG and its embedded miR-497 and miR-195 are proved to play significant roles in many types of human cancers, but their roles in tamoxifen-resistant breast cancer remain unknown. The results indicate that MIR497HG deficiency induces breast cancer progression and tamoxifen resistance by inducing downregulation of miR-497/195. miR-497/195 coordinately represses five positive PI3K-AKT regulators (MAP2K1, AKT3, BCL2, RAF1, and CCND1), resulting in inhibition of PI3K-AKT signaling, and PI3K-AKT inhibition in tamoxifen-resistant cells restored tamoxifen responsiveness. Furthermore, ER α binds the MIR497HG promoter to activate its transcription in an estrogen-dependent manner. ZEB1 interacts with HDAC1/2 and DNMT3B at the MIR497HG promoter, resulting in promoter hypermethylation and histone deacetylation. The findings reveal that ZEB1-induced MIR497HG depletion contributes to breast cancer progression and tamoxifen resistance through PI3K-AKT signaling. MIR497HG can be used as a biomarker for predicting tamoxifen sensitivity in patients with ER+ breast cancer.

Potato Processing Industry in China: Current Scenario, Future Trends and Global Impact.

Potatoes play an important role in ensuring food security. During the COVID-19 epidemic, consumption of processed potato products decreased, and consumption of fresh potatoes increased. China is the world's largest potato producer with more than 4.81 million hectares of area under potato production and 90.32 million metric tonnes of potatoes produced in 2018. This accounts for 27.36% of the world's planting area and 24.53% of the world's potato production. The proportion of potatoes processed in China was about 12% in 2017, mostly dominated by starch production. However, the recent policy of the Chinese government to popularise potato as a staple food has created new markets for processed potato products other than starch. A very few reports have analysed these future trends of the rapidly growing Chinese potato processing industry and its impact within and outside China. This paper provides an overview of the latest developments with a focus on processed potato products such as potato chips, French fries and dehydrated potatoes, and also, due to the unique Chinese diet culture, it highlights the need for more scientific research dedicated towards the development of novel potato-based healthy foods.

A new method for establishing operative channels in unilateral biportal endoscopic surgery: Technical notes and preliminary results.

BACKGROUND: The unilateral biportal endoscopic (UBE) technique has been widely used in spine surgery. At present, a traditional rigid working channel is available for the UBE system. A metal semicircular canal is located in the working channel. However, due to the metal material of the working channel, arthroscopy and instruments are constrained from moving in UBE surgery. Additionally, an assistant is needed during the procedure to hold the traditional working channel. OBJECTIVE: For simplicity of operation and convenient movement of the arthroscopy and instrument, we describe a new method for establishing operative channels in UBE surgery. METHODS: We retrospectively reviewed 50 patients who underwent unilateral biportal endoscopic discectomy (UBED) from February 2020 to August 2020 via our new method. The Oswestry Disability Index (ODI) and visual analogue scale (VAS) score were measured preoperatively and 1 month, 3 months, 6 months and 12 months postoperatively. Statistical comparisons were made using analysis of covariance and paired t tests. RESULTS: The VAS scores for back pain at the five time points were 5.20 ± 2.57, 1.96 ± 0.95, 1.50 ± 0.84, 1.64 ± 1.08 and 1.18 ± 0.39. The leg pain VAS scores were 7.02 ± 2.25, 2.02 ± 1.27, 1.48 ± 0.89, 1.32 ± 0.79 and 0.88 ± 0.52. The ODI values were 51.08 ± 19.97, 19.62 ± 15.51, 8.26 ± 7.40, and 7.54 ± 6.42 to 3.24 ± 1.10. The postoperative ODIs and VAS scores of low back pain and leg pain were significantly lower than those before surgery, and differences were statistically significant (all p< 0.05). The pressure of the closed outflow was significantly higher than that of the open outflow (37.35 ± 13.11 mm Hg vs. 24.55 ± 12.64 mm Hg p= 0.003). After we tightened the infusion strap to open the outflow, the pressure decreased significantly (26.4 ± 14.08 mm Hg vs. 37.35 ± 13.11 mm Hg p= 0.015). There were 2 cases of complications, including 1 case of postoperative recurrence and 1 case of dural tears. CONCLUSION: This study demonstrates the technical feasibility, safety, and efficacy of modified channel establishment in UBE surgery.

Characterization and phylogenetic analysis of the complete chloroplast genome of Saussurea sagittifolia (Asteraceae, Cardueae).

The species of Saussurea sagittifolia Y. S. Chen & S. R. Yi belongs to the family Asteraceae (Cardueae). The complete chloroplast genome of S. sagittifolia was assembled and annotated for the first time in this study. The complete chloroplast genome of S. sagittifolia was 152,535 bp, including a large single-copy (LSC) region of 83,511 bp, a small single-copy (SSC) region of 18,632 bp, and a pair of inverted repeats (IRs) of 25,196 bp. The overall GC content of the chloroplast genome was 37.7%. The chloroplast genome encoded 131 genes, including 87 protein-coding genes, 36 tRNA genes, and eight rRNA genes. Phylogenetic analysis based on complete chloroplast sequences revealed that it related closely to Saussurea medusa.

A novel method of manual positioning based on anatomical mark (shoulder-to-shoulder) to prevent postoperative leg-length discrepancy for femoral neck fractures in hip arthroplasty.

Objective: To determine whether the two lower extremities are of equal length after hip arthroplasty for femoral neck fractures, we developed a novel method of manual positioning based on anatomical mark (shoulder-to-shoulder) in hip arthroplasty. Methods: Patients with femoral neck fractures requiring hip arthroplasty from July 2020 to March 2022 in the orthopedic department of Jinjiang Municipal Hospital, Fujian Province, China were recruited. Hip arthroplasty was performed using the proposed "shoulder-to-shoulder" method of manual positioning based on anatomical mark in 52 patients with femoral neck fractures who met the inclusion criteria. "Shoulder-to-shoulder" was achieved by alignment of the marked femoral "shoulder" and the "shoulder" of prosthesis stem. There were 16 male and 36 female patients, with 27 undergoing total hip arthroplasty (THA) and 25 undergoing hip hemiarthroplasty (HA). The fractures were categorized according to the Garden classification: type II, type III, and type IV in 5, 11, and 36 patients, respectively. The vertical distance from the apex of the medial margin of the femoral trochanter to the tear drop line on both sides which was regarded as the length of both limbs were compared via postoperative imaging, and the apex-shoulder distance on the ipsilateral side measured via postoperative imaging was compared with those measured intraoperatively. Results: All patients completed the surgery successfully. The measurement results for the lower extremities after THA were as follows: contralateral group, 43.87 ± 5.59 mm; ipsilateral group, 44.64 ± 5.43 mm. The measurement results for the lower extremities after HA were as follows: contralateral group, 45.18 ± 7.82 mm; ipsilateral group, 45.16 ± 6.43 mm. The measurement results for the lower extremities after all arthroplasties were as follows: contralateral group, 44.50 ± 6.72 mm; ipsilateral group, 44.89 ± 5.90 mm. The results for the apex-shoulder distance were as follows: postoperative imaging, 19.44 ± 3.54 mm; intraoperative apex-shoulder distance, 27.28 ± 2.84 mm. Statistical analysis results indicated no statistically significant difference in the postoperative bilateral lower extremity length after hip arthroplasty (P = 0.75), while a statistically significant difference was found between the intraoperative and postoperative imaging measurements of the apex-shoulder distance (P < 0.01). Conclusion: The novel method of manual positioning based on anatomical mark (shoulder-to-shoulder) for femoral neck fractures in hip arthroplasty is simple and accurate, making it effective for preventing postoperative bilateral leg length discrepancy.

Ankylosing spondylitis complicated with andersson lesion in the lower cervical spine: A case report.

BACKGROUND: Andersson lesion (AL) is an uncommon complication in ankylosing spondylitis (AS), which is characterized by nonneoplastic bone destruction and often appears as bone destruction and sclerosis in the vertebral body and/or the area involving the intervertebral disc. According to the literature, Andersson lesion commonly occur in the thoracic and lumbar spine and rarely in the cervical spine. CASE SUMMARY: This case involved a 78-year-old man with a long history of AS who developed AL in the cervical spine (C5/6 and C6/7). One-stage anterior-posterior approach surgery was successfully performed. At the 6-month follow-up, the pain was significantly reduced, and the limb function was gradually improved. CONCLUSION: AL uncharacteristically appears in the cervical spine and tends to be misdiagnosed as vertebral metastases or spinal tuberculosis. Posterior combined with anterior surgery achieves solid biological stabilization in the treatment of AL bone destruction.

Light Field Intensification in Optical Films Induced by Intercoupling of Defects and Organic Contamination.

Based on the finite-difference time-domain method, light field intensification in optical films due to the intercoupling of defects and organic contamination was analyzed. The results show that the intercoupling between the defect and the organic contamination droplet leads to an increase in the local electric field and the coupling effect enhances with the decreasing distance between the defect and the organic contamination droplet and the increasing diameter of the organic contamination droplet. The coupling effect of the defect and the organic contamination layer depends on not only the thickness of the organic contamination layer but also the refractive index of the organic contamination layer. With the thickness and the refractive index of the organic contamination layer increasing, the peak value of the electric field decreases. This work deepens the physical understanding of the degradation mechanism of laser-induced damage in optical thin films used in vacuum.

Clinical comparison of three-dimensional exoscope vs. operative microscope in transforaminal lumbar interbody fusion: A retrospective case-control study.

Purpose: Here, we sought to determine the safety and feasibility of three-dimensional exoscope (3D EX). We compared data on surgery, complications, postoperative drainage, hematology, and clinical outcomes in the group that underwent transforaminal lumbar interbody fusion (TLIF) using an operative microscope (OM) relative to those treated using 3D EX. Methods: We retrospectively reviewed records on 74 patients who underwent one- or two-level TLIF from August 2019 to October 2020. Repeated measures analysis of variance was used to compare pre- and post-operative visual analogue scale (VAS) scores and oswestry disability index (ODI). We used analysis of covariance to compare pre- and post-operative erythrocyte count (RBC), hemoglobin (Hb), and hematocrit (Hct). Independent sample t-tests was used to compare postoperative drainage volume, total blood loss (TBL), visible blood loss (VBL) and hidden blood loss (HBL). Results: There were no significant differences in VAS and ODI scores between the two groups at all time points (all p > 0.05). RBC and HBL did not differ significantly between the two groups (all p > 0.05). There were significant differences in postoperative drainage volume,TBL, Hb, and Hct values when using 3D EX relative to OM in two-level TLIF (all p < 0.05), but not for one-level TLIF (all p > 0.05). The two groups differed significantly with regards to VBL when used for one- or two-level TLIF (all p < 0.05). Conclusion: Our data show that 3D EX is a suitable alternative to OM in TLIF. Relative to OM, 3D EX has important strengths in reducing perioperative bleeding in two-level TLIF.

Self-compassion and resilience mediate the relationship between childhood exposure to domestic violence and posttraumatic growth/stress disorder during COVID-19 pandemic.

BACKGROUND: Studies have indicated that childhood exposure to domestic violence is a common factor in posttraumatic growth (PTG) and posttraumatic stress disorder (PTSD), but it is unclear whether PTG and PTSD share a common/different underlying mechanism. AIM: To explore the common/different underlying mechanism of PTG and PTSD. METHODS: Between February 12 and 17, 2020, a nationwide cross-sectional online survey was conducted in China among 2038 university students, and a self-administered questionnaire was used for the data collection. The data included demographic characteristics, such as age, gender, and subjective social economic status, and childhood exposure to domestic violence scale that was selected from the Chinese version of revised Adverse Childhood Experiences Question, Self-compassion Scale, Connor-Davidson Resilience Scale, Posttraumatic Growth Inventory, and the Abbreviated PTSD Checklist-Civilian version. A structural equation model was used to test the hypotheses. RESULTS: Exposure to domestic violence was significantly associated with PTG and PTSD via a 1-step indirect path of self-compassion (PTG: ß = -0.023, 95%CI: -0.44 to -0.007; PTSD: ß = 0.008, 95%CI: 0.002, 0.014) and via a 2-step indirect path from self-compassion to resilience (PTG: ß = -0.008, 95%CI: -0.018 to -0.002; PTSD: ß = 0.013, 95%CI: 0.004-0.024). However, resilience did not mediate the relationship between exposure to domestic violence and PTG and PTSD. CONCLUSION: PTG and PTSD are common results of childhood exposure to domestic violence, which may be influenced by self-compassion and resilience.

[Effect of cropping patterns onbacterial community diversity and metabolic function in rhizosphere soil of Angelica sinensis]. / ç§æ¤æ¨¡å¼å¯¹å½“å½’æ ¹é™ ç»†èŒç¾¤è½å¤šæ ·æ€§åŠä»£è°¢é€šè·¯çš„å½±å“.

The sustainable development of Angelica sinensis industry is seriously restricted by continuous cropping obstacles. In order to explore an efficient cultivation technique for A. sinensis, an experiment with five cropping patterns [A: Pisum sativum (Ps)-A. sinensis (As)-As, control); B: Ps-Triticum aestivum (Ta)-As; C: Ps-Mongolia astragalus (Ma)-As; D: Ps-Solanum tuberosum (St)-As); E: Ps-Fallow (F)-As)] were conducted in major A. sinensis producing areas located in Weiyuan County, Gansu Province. The physicochemical properties and relative abundance of bacterial genomic DNA in rhizosphere soil under different cropping patterns were measured during A. sinensis harvest period to investigate the effects of different cropping patterns on physicochemical properties, bacterial community diversity, and metabolic pathways. The results showed that: 1) the physicochemical properties in A. sinensis rhizosphere soil varied among different cropping patterns. Compared with the control, soil electrical conductivity under C pattern was significantly higher, and lower under B, D and E, CO2 respiration rate for B, C, D and E were significantly increased. 2) Soil bacteria of A. sinensis rhizosphere soil in the five cropping patterns belonged to 26 phyla and 368 genera. The dominant genera were Gemmatimonas from Gemmatimonadetes, Sphingomonas from Proteobacteria, and Subgroup_6 from Acidobacteria. Compared with the control, the relative abundance of Proteobacteria and Actinobacteria under B and C patterns was significantly higher, Acidobacteria in D pattern was significantly lower, while Proteobacteria, Acidobacteria, and Actinobacteria in E pattern was significantly higher. 3) There were significantly negative relations between soil pH, electrical conductivity, contents of organic matter, available nitrogen, phosphorus and potassium with the relative abundance of Proteobacteria in A. sinensis rhizosphere soil across the five cropping patterns. 4) There was significant difference in relative abundance for bacteria of six metabolic pathways under the five cropping patterns. In conclusion, C pattern had a regulating effect on physicochemical properties and bacterial communities in A.sinensis rhizosphere soil, which could be taken as a major practice to overcome the continuous cropping obstacles.

Vascular endothelial growth factor ameliorated palmitate-induced cardiomyocyte injury via JNK pathway.

Enhanced apoptosis of cardiomyocytes in suffering overloaded saturated fatty acids (SFAs) can result in myocardial infarction and cardiac dysfunction. The function of vascular endothelial growth factor (VEGF) in cardiomyocyte protection was not clearly described. To investigate the preservative effects of VEGF sensitization on ceramide-mediated programmed cell death of cardiomyocytes, palmitate-induced injury in H9c2 cells was established as an in vitro model. Results revealed that 0.5 mM palmitate application effectively led to debased viability and activated apoptotic factors. A significant time-dependent relation between PAL and cardiomyocyte injury was observed. The apoptosis rate was increased greatly after 16 h of treatment with 0.5 mM PAL. In addition, cell viability was restored by VEGF overexpression during treatment with 0.5 mM PAL. Reduced apoptosis rate and expression of caspase 3, Bax, and NF-κB p65 were observed in this process, while boosted Bcl-2, p-JNK/JNK expression and activity of caspase 3 were checked. However, p-ERK/ERK levels did not exhibit a significant change. These findings indicated the protective effects of VEGF in confronting the ceramide-induced cardiomyocyte apoptosis, and would devote therapeutic targets for cardiovascular safeguard in dealing with fatty acid stress.

Hsp90-associated DNA replication checkpoint protein and proteasome-subunit components are involved in the age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of vision loss worldwide. However, the mechanisms involved in the development and progression of AMD are poorly delineated. We aimed to explore the critical genes involved in the progression of AMD. METHODS: The differentially expressed genes (DEGs) in AMD retinal pigment epithelial (RPE)/choroid tissues were identified using the microarray datasets GSE99248 and GSE125564, which were downloaded from the gene expression omnibus database. The overlapping DEGs from the two datasets were screened to identify DEG-related biological pathways using gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The hub genes were identified from these DEGs through protein-protein interaction network analyses. The expression levels of hub genes were evaluated by quantitative real-time polymerase chain reaction following the induction of senescence in ARPE-19 with FK866. Following the identification of AMD-related key genes, the potential small molecule compounds targeting the key genes were predicted by PharmacoDB. Finally, a microRNA-gene interaction network was constructed. RESULTS: Microarray analyses identified 174 DEGs in the AMD RPE compared to the healthy RPE samples. These DEGs were primarily enriched in the pathways involved in the regulation of DNA replication, cell cycle, and proteasome-mediated protein polyubiquitination. Among the top ten hub genes, HSP90AA1, CHEK1, PSMA4, PSMD4, and PSMD8 were upregulated in the senescent ARPE-19 cells. Additionally, the drugs targeting HSP90AA1, CHEK1, and PSMA4 were identified. We hypothesize that Hsa-miR-16-5p might target four out of the five key DEGs in the AMD RPE. CONCLUSIONS: Based on our findings, HSP90AA1 is likely to be a central gene controlling the DNA replication and proteasome-mediated polyubiquitination during the RPE senescence observed in the progression of AMD. Targeting HSP90AA1, CHEK1, PSMA4, PSMD4, and/or PSMD8 genes through specific miRNAs or small molecules might potentially alleviate the progression of AMD through attenuating RPE senescence.