Elucidation of the effects of 2,5-hexandione as a metabolite of n-hexane on cognitive impairment in leptin-knockout mice (C57BL/6-Lepem1Shwl/Korl).

Exposure to n-hexane and its metabolite 2,5-hexandione (HD) is a well-known cause of neurotoxicity, particularly in the peripheral nervous system. To date, few studies have focused on the neurotoxic effects of HD on cognitive impairment. Exposure to HD and diabetes mellitus can exacerbate neurotoxicity. There are links among HD, diabetes mellitus, and cognitive impairment; however, the specific mechanisms underlying them remain unclear. Therefore, we aimed to elucidate the neurotoxic effects of HD on cognitive impairment in ob/ob (C57BL/6-Lepem1Shwl/Korl) mice. We found that HD induced cognitive impairment by altering the expression of genes (FN1, AGT, ACTA2, MYH11, MKI67, MET, CTGF, and CD44), miRNAs (mmu-miR15a-5p, mmu-miR-17-5p, and mmu-miR-29a-3p), transcription factors (transcription factor AP-2 alpha [TFAP2A], serum response factor [Srf], and paired box gene 4 [PAX4]), and signaling pathways (ERK/CERB, PI3K/AKT, GSK-3ß/p-tau/amyloid-ß), as well as by causing neuroinflammation (TREM1/DAP12/NF-κB), oxidative stress, and apoptosis. The prevalent use of n-hexane in various industrial applications (for instance, shoe manufacturing, printing inks, paints, and varnishes) suggests that individuals with elevated body weight and glucose levels and those employed in high-risk workplaces have greater probability of cognitive impairment. Therefore, implementing screening strategies for HD-induced cognitive dysfunction is crucial. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-024-00228-1.

Predictive Scoring System for Spontaneous Closure of Infant Ventricular Septal Defect: The P-VSD Score.

Ventricular septal defect (VSD) is a common congenital heart disease. However, consensus on the utility of echocardiography in predicting spontaneous closure (SC) of VSD remains lacking. This study aimed to identify and validate significant predictors of SC through a predictive scoring system. This retrospective study included medical records of 712 echocardiography instances performed on 304 patients diagnosed with VSD from 2016 to 2020 in their first year of life. A novel scoring system for predicting the SC of VSD was developed and validated using another dataset from different hospitals. Of the 304 patients, 215 (70.7%) had perimembranous (PM) VSDs and 89 had muscular (29.3%) VSDs. The median follow-up periods were 36.2 (interquartile range [IQR], 13-59) months and 13.7 9 (IQR, 5-37.4) days for PM and muscular VSDs, respectively. The overall SC rate during follow-up was 29.3%. Pulmonary hypertension (HTN), concomitant left ventricle (LV)-right atrium (RA) shunt, VSD size to aortic valve (AV) annulus size ratio, and left ventricular end-diastolic dimension (LVEDD) z-score were significant risk factors affecting SC of VSD. The "P-VSD" score, a new scoring system, demonstrated an area under the curve for predictability of 0.769. Pulmonary HTN, concomitant LV-RA shunt, LVEDD z-score, and VSD size-to-AV annulus size ratio at diagnosis were significantly associated with non-SC VSD after infancy. The P-VSD score can predict the SC of VSD in clinical settings and simplify the identification and appropriate management of high-risk patients.

USP28 promotes tumorigenesis and cisplatin resistance by deubiquitinating MAST1 protein in cancer cells.

Cisplatin is a chemotherapy drug that causes a plethora of DNA lesions and inhibits DNA transcription and replication, resulting in the induction of apoptosis in cancer cells. However, over time, patients develop resistance to cisplatin due to repeated treatment and thus the treatment efficacy is limited. Therefore, identifying an alternative therapeutic strategy combining cisplatin treatment along with targeting factors that drive cisplatin resistance is needed. CRISPR/Cas9 system-based genome-wide screening for the deubiquitinating enzyme (DUB) subfamily identified USP28 as a potential DUB that governs cisplatin resistance. USP28 regulates the protein level of microtubule-associated serine/threonine kinase 1 (MAST1), a common kinase whose expression is elevated in several cisplatin-resistant cancer cells. The expression level and protein turnover of MAST1 is a major factor driving cisplatin resistance in many cancer types. Here we report that the USP28 interacts and extends the half-life of MAST1 protein by its deubiquitinating activity. The expression pattern of USP28 and MAST1 showed a positive correlation across a panel of tested cancer cell lines and human clinical tissues. Additionally, CRISPR/Cas9-mediated gene knockout of USP28 in A549 and NCI-H1299 cells blocked MAST1-driven cisplatin resistance, resulting in suppressed cell proliferation, colony formation ability, migration and invasion in vitro. Finally, loss of USP28 destabilized MAST1 protein and attenuated tumor growth by sensitizing cells to cisplatin treatment in mouse xenograft model. We envision that targeting the USP28-MAST1 axis along with cisplatin treatment might be an alternative therapeutic strategy to overcome cisplatin resistance in cancer patients.

Safety tests and clinical research on buccal and nasal microneedle swabs for genomic analysis.

Conventional swabs have been used as a non-invasive method to obtain samples for DNA analysis from the buccal and the nasal mucosa. However, swabs may not always collect pure enough genetic material. In this study, buccal and nasal microneedle swab is developed to improve the accuracy and reliability of genomic analysis. A cytotoxicity test, a skin sensitivity test, and a skin irritation test are conducted with microneedle swabs. Polymer microneedle swabs meet the safety requirements for clinical research and commercial use. When buccal and nasal microneedle swabs are used, the amount of genetic material obtained is greater than that from commercially available swabs, and DNA purity is also high. The comparatively short microneedle swab (250 µm long) cause almost no pain to all 25 participants. All participants also report that the microneedle swabs are very easy to use. When genotypes are compared at five SNP loci from blood of a participant and from that person's buccal or nasal microneedle swab, the buccal and nasal microneedle swabs show 100% concordance for all five SNP genotypes. Microneedle swabs can be effectively used for genomic analysis and prevention through genomic analysis, so the utilization of microneedle swabs is expected to be high.

Evaluation of umami taste in Hanwoo with different feed sources by chemical analysis, electronic tongue analysis, and sensory evaluation.

This study aimed to evaluate umami taste in Hanwoo with different feed by chemical analysis, sensory evaluation and an electronic tongue system. Hanwoo cattle were divided into three groups: control group (fed only total mixed ration [TMR]), T1 (fed soybean meal + TMR), and T2 (fed soybean meal + corn-dried distiller's grain with solubles [Corn DDGS] + TMR). The three most abundant fatty acids (C18:1n-9, C16:0, and C18:0) in the T1, T2, and control groups accounted for 83.63%, 86.07%, and 85.52% of the total fatty acid content, respectively. Umami taste-related glutamic acid levels were significantly high in T1 (109.89 mg/kg), followed by T2 (66.66 mg/kg) and control (47.27 mg/kg). Fatty acid levels showed a high correlation with umami taste. The results of this study showed that the amino acid and fatty acid levels had been affected by feed types and soybean- or Corn DDGS-based feed potentially enhanced Hanwoo's umami flavor.

Comprehensive feasibility evaluation of small-diameter 3D templated vascular graft via physical characterizations andin-vivoexperiments.

3D printing (3DP) technology for tissue engineering applications has been extensively studied for materials and processes. However, clinical application to the vascular system was limited owing to mechanical inconsistency and toxicity. Here, we characterized 3D templated artificial vascular grafts (3D grafts), which were fabricated by an integrative method involving 3DP, dip coating, and salt leaching method. The as-fabricated grafts were featured with micrometer-scale porosity enabling tissue-mimetic mechanical softness comparable with native blood vessels. In terms of mechanical properties and water permeability, the fabricated 3D grafts exhibited comparable or superior performances compared to the commercialized grafts. Furthermore, thein-vivostability of the 3D graft was validated through a toxicity test, and the small-diameter 3D graft was transplanted into a rat to confirm the implant's performance. Overall, the experimental results demonstrated the clinical feasibility of the 3D graft with retaining the mechanical biocompatibility and also revealed the possibility of patient-specific customization.

Effect of Janus Kinase 3 Inhibitor on Sebaceous Gland Regeneration during Skin Wound Healing.

BACKGROUND: Janus kinase (Jak) 3 has recently been shown as a beneficial target for the treatment of chronic inflammatory diseases, such as psoriasis and alopecia areata. The role of Jak3 in tissue repair and remodeling is emerging. OBJECTIVE: This study aimed to investigate the role of Jak3 signaling in the remodeling of the sebaceous gland (SG) during skin wound repair, and the development of in vitro SGs. METHODS: Mouse skin tissue (ICR mouse) was obtained from the recovered skin eight days after a 4 mm biopsy punch wound. To observe the role of Jak3, the selective inhibitors WHI-p131 and PF06651600 was administered. Formation of in vitro SG was examined using primary sebocyte cultures obtained postnatally from 3-day-old mice. RESULTS: The data showed that SGs showed highly positive signals with anti-isolectin B4, which also used for detection of angiogenetic vessels and the basal epidermis. Isolectin B4 could be a good indicator of SGs. The Jak3 inhibitors significantly reduced the area and volume of SG remodeling with reduced expression of p-Jak3. In addition, the area of cultured intact SG in vitro was significantly decreased in a concentration-dependent manner by Jak3 inhibition. CONCLUSION: These data showed that Jak3 signaling is a potent regulator to develop SGs. Jak3 inhibition did not decrease the number of sebocytes in SGs but decreased the area and volume of SG remodeling. Therefore, Jak3 inhibition may be a potential target for the treatment of SG hyperplasia and associated skin diseases.

Short-term treatment with risperidone ameliorated 1,2-diacetylbenzene-induced liver dysfunction.

1,2-Diacetylbenze (C10H10O2, DAB) is a potential inducer or activator of toxic mechanisms. DAB exerts high absorption by the gastrointestinal tract and high blood-brain barrier penetration. However, only the effects of DAB on the central nervous system were reported, with a dearth of evidence of DAB's effects on the liver, which is more susceptible to toxic substances. Risperidone, an atypical antipsychotic drug, has been shown to protect against DAB-induced cognitive impairment in an animal model. Risperidone was found to have little or no effect on the liver after short-term administration. The question of whether risperidone can protect against DAB-induced liver dysfunction, particularly after short-term administration, is unknown. Thus, this study aimed to assess the hepatoprotective effects of risperidone on DAB-induced liver dysfunction in male C57BL/6 mice treated with DAB 5 mg/kg for 1 week and risperidone 0.125-0.25 mg/kg for 2 weeks. After exposure to DAB 5 mg/kg for 1 week, we found that DAB induced liver damage by increasing liver function biomarkers (GGT, ALT, and AST), reactive oxygen species, nitric oxide, and proinflammatory cytokines (IL-1α, IL-1ß, IL-6, IL-12, and TNF- α), activating apoptosis (elevated Caspase-3 and Bax levels and reduced Bcl2 level), TLR4/JNK/NF-κB, Jak2/Stat5 pathways, and suppressing Jak2/Stat3 and IRS1/PI3K/AKT/MDM2 pathways. After a 2-week course of treatment, risperidone was able to lessen these effects; the higher dose (0.25 mg/kg) appeared to be more effective than the lower dose (0.125 mg/kg). To strengthen findings from in vivo analysis, in silico analysis also found three targets (Stat3, Caspase-3, AKT, IL-1ß), two miRNAs (miR-26b-5p and miR-34a-5p), two transcription factors (NFKB1 and NFKB2), and numerous pathways ("AGE-RAGE signaling pathway in diabetic complications", "hepatitis B", "alcoholic liver disease", "apoptosis", and "liver cirrhosis") as the key molecular processes involved in the pathogenesis of DAB-induced liver damage and targeted by risperidone. The physicochemical characteristics and pharmacokinetics of DAB and risperidone also support the toxic effects of DAB and the beneficial properties of risperidone in the liver. In conclusion, these findings reflect the therapeutic effects of risperidone on DAB-induced liver dysfunction after 1 week and 2 weeks exposure to DAB and risperidone, respectively.

VERD: Emergence of Product-Based Video E-Commerce Retrieval Dataset from User's Perspective.

Customer demands for product search are growing as a result of the recent growth of the e-commerce market. According to this trend, studies on object-centric retrieval using product images have emerged, but it is difficult to respond to complex user-environment scenarios and a search requires a vast amount of data. In this paper, we propose the Video E-commerce Retrieval Dataset (VERD), which utilizes user-perspective videos. In addition, a benchmark and additional experiments are presented to demonstrate the need for independent research on product-centered video-based retrieval. VERD is publicly accessible for academic research and can be downloaded by contacting the author by email.

Risperidone ameliorated 1,2-Diacetylbenzene-induced cognitive impairments in mice via activating prolactin signaling pathways.

Cognitive impairment and organic solvent exposure have been becoming public health concerns due to an increasingly aging population, increased life expectancy, urbanization, and industrialization. Converging evidence indicates the link between 1,2-diacetylbenzene (DAB), prolactin (PRL), risperidone, and cognitive impairment. However, these relationships remain unclear. We investigated the therapeutic properties of risperidone in DAB-induced cognitive impairment using both in vivo and in silico methods. Risperidone alleviated DAB-induced cognitive impairment in hippocampal mice, possibly by inhibiting GSK-3ß, ß-amyloid, CDK5, BACE, and tau hyperphosphorylation. Risperidone also attenuated the activation of TREM-1/DAP12/NLRP3/caspase-1/IL-1ß, and TLR4/NF-κB pathways caused by DAB. Furthermore, risperidone inhibited DAB-induced oxidative stress, advanced glycation end products, and proinflammatory cytokines, as well as increased the expression of Nrf2, IL-10, Stat3, MDM2, and catalase activity. On the other hand, risperidone activated the expression of IRS1, PI3K, AKT, BDNF, Drd2, Scna5, and Trt as well as reduced the Bax/Bcl2 ratio and Caspase-3 levels. In silico analyses identified the prolactin signaling pathway, miR-155-5p, miR-34a-5p, and CEBPB as the main molecular mechanisms involved in the pathophysiology of DAB-induced cognitive impairment and targeted by risperidone. Our results suggest that risperidone could be used to treat cognitive impairment caused by organic solvents, especially DAB.

Effects of Familial Relationships on School Adjustment of Adolescents and Young Adults With Congenital Heart Disease.

BACKGROUND: As more than 85% of patients with congenital heart disease (CHD) have grown to adulthood through improvement in treatment and surgery, the difficulties they experience are expanding into areas related to daily life. Accordingly, adjustment to school in adolescents and young adults (AYAs) with CHD is of increasing interest and is influenced by familial factors. OBJECTIVE: This was a cross-sectional descriptive study to examine the effects of parental positive emotional expressiveness and sibling relationships on school adjustment of AYAs with CHD. METHODS: In this study, a self-reported questionnaire survey was used to collect the data. The participants were 104 AYAs with CHD aged 13 to 21 years who were attending school and had siblings. RESULTS: Maternal positive emotional expressiveness ( r = 0.584, P < .01), paternal positive emotional expressiveness ( r = 0.584, P < .01), and sibling warmth/closeness ( r = 0.478, P < .01) were significantly correlated with school adjustment. However, the results of multiple regression analysis showed that only maternal positive emotional expressiveness (ß = 0.459, P < .05) and sibling warmth/closeness (ß = 0.236, P < .05) were significantly associated with school adjustment. CONCLUSIONS: Adolescents and young adults with CHD who reported higher maternal positive emotional expressiveness and sibling warmth/closeness exhibited better school adjustment. Findings suggest that intervention programs to increase parental positive expressiveness and enhance warmth/closeness of sibling relationships may contribute to improving school adjustment.

Successful Heart Transplant in Dilated Cardiomyopathy Associated With Alström Syndrome: A Case Report.

Alström syndrome is a rare, multisystemic genetic disorder, and dilated cardiomyopathy occurs in approximately two-thirds of patients with this condition. Because of donor organ shortage and unfavorable prognosis of multiple organ dysfunction, heart transplant is not the most desirable therapeutic option for patients with dilated cardiomyopathy with Alström syndrome. However, eliminating heart dysfunction elements at an appropriate time itself plays a pivotal role in preventing or even reversing other organ failures. Herein, we report the case of a 17-year-old boy who underwent successful isolated heart transplant despite severe liver dysfunction.

Heart Transplantation in a Patient with Complex Congenital Heart Disease, Physiologic Single Lung, and Severe Pulmonary Hypertension.

Here we report a case of successful heart transplantation (HT) in a patient with high risk on HT due to her complex congenital heart disease and its consequent complications; physiologic single lung and severe pulmonary arterial hypertension. HT was successfully performed in our patient using meticulous perioperative management techniques, such as control of collateral vessels, appropriate donor selection, pulmonary vasodilator therapy, post-transplant extracorporeal membranous oxygenation support, and atrial septostomy for right ventricular unloading.

Multispectral Benchmark Dataset and Baseline for Forklift Collision Avoidance.

In this paper, multispectral pedestrian detection is mainly discussed, which can contribute to assigning human-aware properties to automated forklifts to prevent accidents, such as collisions, at an early stage. Since there was no multispectral pedestrian detection dataset in an intralogistics domain, we collected a dataset; the dataset employs a method that aligns image pairs with different domains, i.e. RGB and thermal, without the use of a cumbersome device such as a beam splitter, but rather by exploiting the disparity between RGB sensors and camera geometry. In addition, we propose a multispectral pedestrian detector called SSD 2.5D that can not only detect pedestrians but also estimate the distance between an automated forklift and workers. In extensive experiments, the performance of detection and centroid localization is validated with respect to evaluation metrics used in the driving car domain but with distinct categories, such as hazardous zone and warning zone, to make it more applicable to the intralogistics domain.

Performance evaluation of biodegradable polymer sirolimus and ascorbic acid eluting stent systems.

The purpose of this study was to evaluate the performance of biodegradable polymer sirolimus and ascorbic acid eluting stent systems with four commercially available drug-eluting stents (DES). We investigated the characterization of mechanical properties by dimension, foreshortening, recoil, radial force, crossing profile, folding shape, trackability, and dislodgement force. Additionally, we identify the safety and efficacy evaluation through registry experiments. Each foreshortening and recoil of D + Storm® DES is 1.3 and 3.70%, which has better performance than other products. A post-marketing clinical study to evaluate the performance and safety of D + Storm® DES is ongoing in real-world clinical settings. Two hundred one patients were enrolled in this study and have now completed follow-up for up to 1 month. No major adverse cardiovascular event (MACE) occurred in any subjects, confirming the safety of D + Storm® DES in the clinical setting. An additional approximately 100 subjects will be enrolled in the study and the final safety profile will be assessed in 300 patients. In conclusion, this study reported the objective evaluation of DES performance and compared the mechanical responses of four types of DES available in the market. There is little difference between the four cardiovascular stents in terms of mechanical features, and it can help choose the most suitable stent in a specific clinical situation if those features are understood. Graphical abstract.

In silico identification of the potential molecular mechanisms involved in protective effects of prolactin on motor and memory deficits induced by 1,2-Diacetylbenzene in young and old rats.

We aimed to identify the molecular mechanisms through which prolactin protects against 1,2-Diacetylbenzene (DAB)-induced memory and motor impairments. The gene expression omnibus database (no. GSE119435), transcriptomic data, GeneMANIA, ToppGeneSuite, Metascape, STRING database, Cytoscape, and Autodock were used as the core tools in in-silico analyses. We observed that prolactin may improve memory and motor deficits caused by DAB via 13 genes (Scn5a, Lmntd1, LOC100360619, Rgs9, Srpk3, Syndig1l, Gpr88, Egr2, Ctxn3, Drd2, Ttr, Gpr6, and Ecel1) in young rats and 9 genes (Scn5a, Chat, RGD1560608, Ucma, Lrrc31, Gpr88, Col1a2, Cnbd1, and Ttr) in old rats. Almost all of these genes were downregulated in both young and old rats given DAB, but they were increased in both young and old rats given prolactin. Co-expression interactions were identified as the most important interactions (83.2 % for young rats and 100 % for old rats). The most important mechanisms associated with prolactin's ability to counteract DAB were identified, including "learning and memory," and "positive regulation of ion transport" in young rats, as well as "acetylcholine related pathways," "inflammatory response pathway," and "neurotransmitter release cycle" in old rats. We also identified several key miRNAs associated with memory and motor deficits, as well as prolactin and DAB exposure (rno-miR-141-3p, rno-miR-200a-3p, rno-miR-124-3p, rno-miR-26, and rno-let-7 families). The most significant transcription factors associated with differentially expressed gene regulation were Six3, Rxrg, Nkx26, and Tbx20. These findings will contribute to our understanding of the processes through which prolactin's beneficial effects counteract DAB-induced memory and motor deficits.

Curcumin-Attenuated TREM-1/DAP12/NLRP3/Caspase-1/IL1B, TLR4/NF-κB Pathways, and Tau Hyperphosphorylation Induced by 1,2-Diacetyl Benzene: An in Vitro and in Silico Study.

We aimed to evaluate the effects of 1,2-diacetylbenzene (DAB) and curcumin on neuroinflammation induced by DAB via triggering receptor expressed on myeloid cells 1 (TREM-1), Toll-like receptor 4 (TLR4), and NLR family pyrin domain containing 3 (NLP3)/calcium-dependent activator protein for secretion 1 (CAPS1)/interleukin 1 beta (IL1B) pathways; tau hyperphosphorylation; reactive oxygen species (ROS); and advanced glycation end-product (AGE) in microglia cells; and explore the molecular mechanisms involved in the key genes induced by DAB and targeted by curcumin in silico analysis. In this study, Western blot, quantitative polymerase chain reaction, and immunocytochemistry were used as the key methods in vitro. In silico analysis, GeneMANIA, ToppFun feature, Metascape, CHEA3, Cytoscape, Autodock, and MIENTURNET were the core approaches used. Curcumin inhibited both the DAB-induced TREM-1/DAP12/NLRP3/caspase-1/IL1B pathway and the TLR4/NF-κB pathway. In BV2 cells, curcumin inhibited ROS, AGE, hyperphosphorylation, glycogen synthase kinase-3ß (GSK-3ß), and ß-amyloid while activating nuclear factor erythroid 2-related factor 2 (Nrf2) expression. In silico studies showed that tumor necrosis factor (TNF), IL6, NFKB1, IL10, and IL1B, as well as MTF1 and ZNF267, were shown to be important genes and transcription factors in the pathogenesis of cognitive impairment produced by DAB and curcumin. Three significant miRNAs (hsa-miR-26a-5p, hsa-miR-203a-3p, and hsa-miR-155-5p) implicated in the etiology of DAB-induced cognitive impairment and targeted by curcumin were also identified. Inflammation and cytokine-associated pathways, Alzheimer's disease, and cognitive impairment were characterized as the most significant biological processes implicated in genes, miRNAs, and transcription factors induced by DAB and targeted by curcumin. Our findings provide new insight into fundamental molecular mechanisms implicated in the pathogenesis of cognitive impairment caused by DAB, particularly the effects of neuroinflammation. Furthermore, this study suggests that curcumin might be a promising therapeutic molecule for cognitive impairment treatment through modulating neuroinflammatory responses.

Assessment of Device Neoendothelialization With Cardiac Computed Tomography Angiography After Transcatheter Closure of Atrial Septal Defect.

BACKGROUND: Although the transcatheter closure of atrial septal defect was established as the treatment of choice several decades ago, the process of device neoendothelialization (NE) in humans is not well understood. We aimed to measure the extent of device NE using cardiac computed tomography angiography and analyze its risk factors. METHODS: Between January 2005 and February 2021, we retrospectively reviewed 164 devices of 112 patients on cardiac computed tomography angiography. We investigated device shape, contrast opacification within the device that differentiated device NE, and device-related thrombosis or vegetation. Risk factor analysis for major adverse cardiovascular events and incomplete NE according to the postprocedural period was performed. RESULTS: Seventy patients (62.5%) were women, with a median (range) age at the time of device closure of 44.5 (0.6-79.2) years. The mean (±SD) defect size was 16.6 (±7.8) mm, and patients were followed for 35.9±33.9 months. After 6 months of device implantation, 35% of the devices (42/120) had incomplete NE. The intensity of intradevice opacification shifted from complete to partial or nonopacification over time (P<0.001), and a similar pattern was observed in the shunt flow (P<0.001). The bulkiness of devices also decreased in proportion to the postprocedural period (P<0.001). Risk analysis revealed device diameter (hazard ratio, 1.18 [95% CI, 1.04-1.27]; P<0.001) as the only significant factor of incomplete NE and major adverse events. CONCLUSIONS: Incomplete NE of atrial septal defect devices was identified on cardiac computed tomography angiography in significant numbers after 6 months of the procedure. The device diameter was related to incomplete NE and major adverse events. Further prospective and multicenter studies are warranted to validate this new assessment of device NE.

1,2-Diacetylbenzene impaired hippocampal memory by activating proinflammatory cytokines and upregulating the prolactin pathway: An in vivo and in vitro study.

Memory loss is the most common occurrence of dementia in the elderly population. Evidence shows 1,2-Diacetylbenzene (DAB) can exacerbate cerebral dysfunction. The molecular mechanisms involved in DAB actions in the hippocampus have not been well elucidated to date. qPCR, western blot, Morris water maze, and RNAseq analysis were used to identify the association between inflammation and hyperphosphorylated tau in male DAB-treated mice (1 or 5 mg/kg/day), rats (3 mg/kg/day), in vitro BV2 microglial cells (1 or 5 µM), and the hippocampal transcriptome of male DAB-treated rats. We found that DAB induces memory deficits by activating pro-inflammatory cytokines as well as down-regulating memory and learning genes. Several genes involved in learning, memory, and behavior induced by DAB (e.g., PRL, Pit-1, PRLR, Ttr, Notch2, Ntsr1, C5ar2, Cd74) were not changed or downregulated in young rats, but upregulated in old rats. Detoxification pathways were upregulated in young rats treated with DAB, whereas prolactin (PRL) signaling pathways were upregulated in old DAB-treated rats. Further work is needed to gain a better understanding of the roles of PRL during aging.