A synergistic effect of herb and acupuncture on the methamphetamine.

Background: Herbal medicine Ja-Geum-Jeong (JGJ) has been used for the treatment of detoxification in Eastern Asia. However, the mechanisms involved are not clearly defined. The purpose of the present study was to investigate if herb medication inhibits Methamphetamine (METH)'s reinforcing effect and also examined if a combination of herb medication and acupuncture produces a synergistic effect on METH. Methods: Male Sprague-Dawley rats were given acute METH intraperitoneally and the locomotor activity and ultrasonic vocalization (USV) calls were measured. Rats were administered JGJ orally and acupuncture was given at HT7 or SI5. Monosodium glutamate (MSG) and gamma-aminobutyric acid (GABA) agonists were injected into the Central amygdala (CeA) to investigate a possible neuroscientific mechanism. Tyrosine hydroxylase (TH) and fast scan cyclic voltammetry (FSCV) were measured to immunohistochemically and electrically confirm the behavioral data. Results: Locomotor activity and USV calls were increased by METH (P < 0.05) and these increases were inhibited by JGJ (P < 0.05). Also, JGJ had no effect on the normal group given saline, and acupuncture at SI5 acupoint, but not at HT7 acupoint, produced a synergistic effect when combined with JGJ (P < 0.05). The JGJ's inhibition was blocked by the inactivation of CeA (P < 0.05), and MSG mimicked JGJ (P < 0.05). TH and FSCV measures showed the same pattern with the behavioral data (P < 0.05). Conclusion: Results of the present study suggest that JGJ had inhibitory effects on the METH which was mediated through the activation of CeA and that combination of acupuncture and herb produced synergistic effect.

Successful desensitization to atezolizumab-induced near-fatal anaphylaxis in patients with hepatocellular carcinoma: A case report and literature review.

Atezolizumab, a humanized antiprogrammed death ligand 1 monoclonal immunoglobulin G1 antibody, is a targeted therapeutic drug known as an immune checkpoint inhibitor. It is currently used to treat various types of cancer, including unresectable hepatocellular carcinoma (HCC), nonsmall cell lung cancer, urothelial cancer, and breast cancer, and is becoming a therapeutic option in the forefront of oncology treatment. However, it may sometimes lead to undesirable adverse reactions owing to the activation of immune responses in various organs. Cutaneous adverse reactions to atezolizumab are well known; however, cases of anaphylaxis are very rare. In this report, we present the first case of HCC who experienced near-fatal anaphylaxis to atezolizumab in South Korea.

Near-infrared laser diode mitigates Aß1-42-induced neurodegeneration in cortical neurons.

Alzheimer's disease, a prevalent neurodegenerative condition primarily affecting older adults, remains incurable. Its principle pathological hallmark is the accelerated accumulation of amyloid ß (Aß) protein. This study investigates the potential of photobiomodulation using near infrared light to counteract Aß1-42-induced synaptic degeneration and neurotoxicity. We focused on the effect of 808 nm near-infrared laser diode (LD) on Aß1-42 cytotoxicity in primary cultured cortical neurons. We assessed cell survival using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, observing substantial benefits from LD irradiation with a power of 10 mW and a dose of 30 J. Cells exposed to Aß1-42 exhibited morphological changes indicative of synaptic damage and a significant decrease in the number of postsynaptic density protein-95 (PSD-95) contacts, which were significantly improved with near-infrared LD therapy. Furthermore, this therapy reduced Aß and phosphorylated tau (P-tau) protein accumulation. Additionally, near-infrared LD irradiation substantially lessened the Aß1-42-induced rise in glial fibrillary acid protein (GFAP) and ionized calcium-binding adaptor molecule 1 (IBA1) in astrocytes and microglia. Remarkably, near-infrared LD irradiation effectively inhibited phosphorylation of key proteins involved in Aß1-42-induced necroptosis, namely Receptor-interacting protein kinase-3 (RIP3) and Mixed Lineage Kinase domain-Like protein (MLKL). Our findings suggest that near-infrared LD treatment significantly reduces neurodegeneration by reducing glial overactivation and neuronal necroptosis triggered by Aß1-42. Thus, near-infrared LD treatment emerges as a promising approach for slowing or treating Alzheimer's disease, offering new avenues in its management.

Long-term acclimation to organic carbon enhances the production of loliolide from Scenedesmus deserticola.

Production of functional biocompounds from microalgae has garnered interest from different industrial sectors; however, their overall productivity must be substantially improved for commercialization. Herein, long-term acclimation of Scenedesmus deserticola was conducted using glucose as an organic carbon source to enhance its heterotrophic capabilities and the production potential of loliolide. A year-long acclimation on agar plates led to the selection of S. deserticola HS4, which exhibited at least 2-fold increase in loliolide production potential; S. deserticola HS4 was subjected to further screening of its cultivation conditions and fed-batch cultivation was subsequently performed in liter-scale reactors. While S. deserticola HS4 exhibited shifts in cellular morphology and biochemical composition, the results suggested a substantial increase in its loliolide productivity regardless of trophic modes. Collectively, these results highlight the potential of long-term acclimation as an effective strategy for improving microalgal crops to align with industrial production practices.

Defying "IL-11ness" by inhibiting inflammation: Strategy for health and longevity.

Organismal aging involves several hallmark pathways, including chronic inflammation and metabolic dysfunction. However, the origin of age-related inflammation is incompletely understood. In a recent study published in Nature,1 Widjaja et al. show that blocking the age-related increase in IL-11 restores immune-metabolic homeostasis and extends healthspan and lifespan in mice.

Validity and Reliability of the Korean Versions of the 9- and 19-Item Wearing-Off Questionnaires in Parkinson's Disease.

BACKGROUND AND PURPOSE: The wearing-off (WO) phenomenon is the most common motor complication in advanced Parkinson's disease (PD), but its identification remains challenging. The 9- and 19-item Wearing-off Questionnaires (WOQ-9 and WOQ-19) are self-assessment tools for motor and nonmotor symptoms that are widely used for WO screening. We produced Korean versions of the WOQ-19 and WOQ-9 (K-WOQ-19 and K-WOQ-9) and investigated their validity and reliability. METHODS: We used the translation-back translation method to produce K-WOQ-19 and K-WOQ-9, which were self-administered by 124 patients with PD. We conducted in-depth 10-minute interviews for confirming the presence of the WO phenomenon, and then stratified the participants into groups with and without WO. Diagnostic accuracy was assessed byanalyzing receiver operating characteristic curves. Concurrent validity was assessed using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) andthe Hoehn and Yahr stage with Spearman's rank correlation analysis. Reliability was assessedbased on test-retest Cohen's kappa (κ) values and intraclass correlation coefficients (ICCs). RESULTS: The optimal cutoff scores on the K-WOQ-19 and K-WOQ-9 for WO screening were 4 and 2, respectively. The test-retest ICCs of K-WOQ-19 and K-WOQ-9 were 0.943 and 0.938, respectively. Nineteen of the combined 20 items in K-WOQ-19 and K-WOQ-9 showed moderate-to-substantial agreement (κ=0.412-0.771, p<0.001). The scores on the translated scales were significantly correlated with MDS-UPDRS IV scores. CONCLUSIONS: K-WOQ-19 and K-WOQ-9 are reliable and valid tools for detecting WO, with optimal cutoff scores of 4 and 2, respectively.

Impacts of Tocolytics on Maternal and Neonatal Glucose Levels in Women With Gestational Diabetes Mellitus.

BACKGROUND: We investigated the impacts of tocolytic agents on maternal and neonatal blood glucose levels in women with gestational diabetes mellitus (GDM) who used tocolytics for preterm labor. METHODS: This multi-center, retrospective cohort study included women with GDM who were admitted for preterm labor from twelve hospitals in South Korea. We excluded women with multiple pregnancies, anomalies, overt DM diagnosed before pregnancy or 23 weeks of gestation, and women who received multiple tocolytics. The patients were divided according to the types of tocolytics; atosiban, ritodrine, and nifedipine group. We collected baseline maternal characteristics, pregnancy outcomes, maternal glucose levels during hospitalization, and neonatal glucose levels. We compared the frequency of maternal hyperglycemia and neonatal hypoglycemia among three groups. A multivariate logistic regression analysis was performed to evaluate the contributing factors to the occurrence of maternal hyperglycemia and neonatal hypoglycemia. RESULTS: A total of 128 women were included: 44 (34.4%), 51 (39.8%), and 33 (25.8%) women received atosiban, ritodrine, and nifedipine, respectively. Mean fasting blood glucose (FBG) (112.3, 109.6, and 89.5 mg/dL, P < 0.001) and 2-hour postprandial glucose (PPG2) levels (145.4, 148.3, and 116.5 mg/dL, P = 0.004) were significantly higher in atosiban and ritodrine group than those in nifedipine group. Even after adjusting for covariates including antenatal steroid use, gestational age at admission, and pre-pregnancy body mass index, there was an increased risk of high maternal mean FBG (≥ 95 mg/dL) and PPG2 (≥ 120 mg/dL) levels in the atosiban and ritodrine group than in nifedipine group. The atosiban and ritodrine groups are also at increased risk of neonatal hypoglycemia (< 47 mg/dL) compared to the nifedipine group with the odds ratio of 4.58 and 4.67, respectively (P < 0.05). CONCLUSION: There is an increased risk of maternal hyperglycemia and neonatal hypoglycemia in women with GDM using atosiban and ritodrine tocolytics for preterm labor compared to those using nifedipine.

Low-temperature pulverization-specific Sargassum horneri extract accelerates wound healing and attenuates inflammation in a mouse burn model.

Burn injuries, affecting local skin disruption as well as inducing systemic inflammatory responses, are presented as a global public health problem. To enhance the effects of burn wound healing, treatment must simultaneously regulate both re-epithelialization and hyperinflammation. Extracts of Sargassum horneri (S. horneri) have shown a potential to enhance skin wound healing through antioxidative properties, immune enhancement, and modulation of inflammatory responses. However, despite its promising application for burn wound healing, specific investigation into S. horneri-derived compounds for enhancing wound healing has not yet been conducted. In this research, we investigated the burn wound-healing effect of the low-temperature pulverization-specific S. horneri extract (LPSHE), which could not be detected using the room-temperature grinding method. In a mouse burn model with third-degree burn injuries, LPSHE accelerated re-epithelialization by promoting the increase in F-actin formation and reduced burn-induced ROS levels. Additionally, LPSHE significantly regulated hyperinflammation by reducing pro-inflammatory cytokines. Further investigation into molecular mechanisms using HaCaT keratinocytes also demonstrated beneficial effects on burn wound healing. Taken together, our findings suggested that LPSHE is a promising therapeutic candidate for enhancing burn wound healing. Furthermore, this research underscored the importance of low-temperature pulverization in discovering novel natural compounds from marine organisms.

Association Between Influenza Vaccination and Acute Kidney Injury Among the Elderly: A Self-Controlled Case Series.

BACKGROUND: Several cases of renal complications, including acute kidney injury (AKI), after influenza vaccination have been reported, but the association remains unproven. We evaluated the association between influenza vaccination and AKI occurrence among the Korean elderly in the 2018-2019 and 2019-2020 seasons. METHODS: We used a large database combining vaccination registration data from the Korea Disease Control and Prevention Agency and claims data from the National Health Insurance Service. The study subjects were patients hospitalized with AKI for the first-time following vaccination among those who received one influenza vaccine in the 2018-2019 or 2019-2020 season. Only those aged 65 or older at the date of vaccination were included. We performed a self-controlled case series study, designating the risk period as 1 to 28 days post-vaccination and the observation period as each influenza season. The adjusted incidence rate ratio (aIRR) was calculated by adjusting for nephrotoxic drug use and influenza infection that may influence AKI occurrence using a conditional Poisson regression model. RESULTS: A total of 16 713 and 16 272 AKI events were identified during the 2018-2019 and 2019-2020 seasons, respectively. The aIRR for AKI was 0.83 (95% confidence interval [CI] = 0.79-0.87) in the 2018-2019 season. The aIRR for the 2019-2020 influenza season was similar to the 2018-2019 season (aIRR = 0.86; 95% CI = 0.82-0.90). CONCLUSIONS: Influenza vaccination is associated with a lower risk of AKI in the elderly over 65. This evidence supports the recommendation of annual influenza vaccination for the elderly. Further studies are needed to determine the biological mechanisms linking the influenza vaccine and AKI.

Initial sarcopenia and body composition changes as prognostic factors in cervical cancer patients treated with concurrent chemoradiation: An artificial intelligence-based volumetric study.

OBJECTIVES: This study aimed to investigate the influence of baseline sarcopenia and changes in body composition on survival during cervical cancer treatment. METHODS: Patients diagnosed with stage IB1-IVB cervical cancer who underwent primary concurrent chemoradiation therapy (CCRT) between 2002 and 2022 were included. The exclusion criteria were prior radical hysterectomy, lack of pretreatment computed tomography (CT) imaging, or significant comorbidities. An artificial intelligence-based automatic segmentation program assessed body composition by analyzing CT images, defining L3 sarcopenia (L3 skeletal muscle index [SMI] <39cm2/m2) and volumetric sarcopenia (volumetric SMI <180.4 cm3/m3). Comparative and multivariate analyses identified the prognostic factors. The impact of body component changes during CCRT was explored. RESULTS: Among 347 patients, there were 125 recurrences and 59 deaths (median follow-up, 50.5 months). Seven patients were excluded from the volumetric sarcopenia analysis because of incomplete baseline CT data, and 175 patients were included in the analysis of body composition changes. Patients with L3 sarcopenia had a lower 5-year progression-free survival (PFS) rate (55.6% vs. 66.2%, p = 0.027), while those with volumetric sarcopenia showed a poorer 5-year overall survival rate (76.5% vs. 85.1%, p = 0.036). Patients with total fat loss during CCRT had a worse 5-year PFS rate than those with total fat gain (61.9% vs. 73.8%, p = 0.029). Multivariate analyses revealed that total fat loss (adjusted hazard ratio [aHR], 2.172; 95% confidence interval [CI], 1.066-4.424; p = 0.033) was a significant factor for recurrence, whereas L3 sarcopenia was not. Volumetric sarcopenia increased the risk of death by 1.75-fold (aHR, 1.750; 95% CI, 1.012-3.025; p = 0.045). CONCLUSIONS: Among patients with cervical cancer undergoing CCRT, initial volumetric sarcopenia and fat loss during treatment are survival risk factors. These findings suggest the potential importance of personalized supportive care, including tailored nutrition and exercise interventions.

Prognostic impact of intraoperative rupture in early-stage epithelial ovarian cancer: an ancillary study of GORILLA-3002.

OBJECTIVE: To evaluate whether intraoperative rupture affects oncological outcomes in patients with early-stage epithelial ovarian cancer (EOC). METHODS: A multicenter retrospective study was conducted on patients with early-stage EOC based on surgical and final pathological reports between 2007 and 2021. Oncologic outcomes were compared between the unruptured group (International Federation of Gynaecology and Obstetrics [FIGO] stage IA/IB) and ruptured group (FIGO stage IC1). The primary endpoint was progression-free survival (PFS). Propensity score matching (PSM) was performed to adjust for the imbalance in prognostic factors between the groups. RESULTS: Overall, 197 (58.3 %) patients comprised the unruptured group (FIGO stage IA/IB), and 141 (41.7 %) were in the intraoperatively ruptured group (FIGO stage IC1). No significant difference in the 5-year PFS was observed between the two groups before PSM (92.65 % vs. 92.80 %, P = 0.93). After PSM, the 5-year PFS showed a noticeable decrease in the ruptured group compared to the unruptured group, although this difference showed borderline statistical significance (96.90 % vs. 89.82 %, P = 0.061). This trend was particularly discernible in cases with aggressive tumor characteristics; intraoperative rupture remained an independent prognostic factor for shorter PFS in patients with high-grade histology (adjusted hazard ratio = 14.4, 95 % confidence interval = 2.8-74.1). CONCLUSIONS: Although not statistically significant, intraoperative rupture may negatively affect PFS in these patients after PSM. Therefore, rupture during surgery should be avoided as it can cause upstaging and unnecessary chemotherapy.

Predicting Neutropenic Sepsis in Patients with Hematologic Malignancy: A Retrospective Case-Control Study.

Neutropenic sepsis (NS) is one of the leading causes of death among patients with hematologic malignancies. Identifying its predictive factors is fundamental for early detection. Few studies have evaluated the predictive factors in relation to microbial infection confirmation, which is clinically important for initiating sepsis treatment. This study aimed to determine whether selected biomarkers (i.e., body temperature, C-reactive protein, albumin, procalcitonin), treatment-related characteristics (i.e., diagnosis, duration of neutropenia, treatment modality), and infection-related characteristics (i.e., infection source, causative organisms) can predict NS in patients with hematologic malignancies. We also aimed to identify the optimal predictive cutoff points for these parameters. This retrospective case-control study used the data from a total of 163 patients (58 in the sepsis group and 105 in the non-sepsis group). We collected data with reference to the day of specimen collection, with which microbial infection was confirmed. Multiple logistic regression was used to determine predictive risk factors and the area under the curve (AUC) of the receiver operating characteristic for the optimal predictive cutoff points. The independent predictors of NS were average body temperature during a fever episode and procalcitonin level. The odds for NS rose by 9.97 times with every 1°C rise in average body temperature (95% confidence interval, CI [1.33, 75.05]) and by 2.09 times with every 1 ng/mL rise in the procalcitonin level (95% CI [1.08, 4.04]). Average body temperature (AUC = 0.77, 95% CI [0.68, 0.87]) and procalcitonin levels (AUC = 0.71, 95% CI [0.59, 0.84]) have fair accuracy for predicting NS, with the optimal cutoff points of 37.9°C and 0.55 ng/mL, respectively. This study found that average body temperature during a fever episode and procalcitonin are useful in predicting NS. Thus, nurses should carefully monitor body temperature and procalcitonin levels in patients with hematologic malignancies to detect the onset of NS.

Oxygen reserve index versus conventional peripheral oxygen saturation for prevention of hypoxaemia: A randomised controlled trial.

BACKGROUND: Hypoxaemia occurs frequently during paediatric laryngeal microsurgery. OBJECTIVE: The oxygen reserve index is a noninvasive and continuous parameter to assess PaO2 levels in the range of 100 to 200 mmHg. It ranges from 0 to 1.0. We investigated whether monitoring the oxygen reserve index can reduce the incidence of SpO2 90% or less. DESIGN: Randomised controlled trial. SETTING: A tertiary care paediatric hospital. PARTICIPANTS: Paediatric patients aged 18 years or less scheduled to undergo laryngeal microsurgery. INTERVENTION: The patients were randomly allocated to the oxygen reserve index or control groups, and stratified based on the presence of a tracheostomy tube. Rescue intervention was performed when the oxygen reserve index was 0.2 or less and the SpO2 was 94% or less in the oxygen reserve index and control groups, respectively. MAIN OUTCOME MEASURE: The primary outcome was the incidence of SpO2 90% or less during the surgery. RESULTS: Data from 88 patients were analysed. The incidence of SpO2 ≤ 90% did not differ between the oxygen reserve index and control groups [P = 0.114; 11/44, 25% vs. 18/44, 40.9%; relative risk: 1.27; and 95% confidence interval (CI): 0.94 to 1.72]. Among the 128 rescue interventions, SpO2 ≤ 90% event developed in 18 out of 75 events (24%) and 42 out of 53 events (79.2%) in the oxygen reserve index and control groups, respectively (P < 0.001; difference: 55.2%; and 95% CI 38.5 to 67.2%). The number of SpO2 ≤ 90% events per patient in the oxygen reserve index group (median 0, maximum 3) was less than that in the control group (median 0, maximum 8, P = 0.031). CONCLUSION: Additional monitoring of the oxygen reserve index, with a target value of greater than 0.2 during paediatric airway surgery, alongside peripheral oxygen saturation, did not reduce the incidence of SpO2 ≤ 90%.

Non-invasive prediction of post-sustained virological response HCC in HCV: A systematic review and meta-analysis.

Background: Despite advances in antiviral therapy for hepatitis C virus (HCV) infection, hepatocellular carcinoma (HCC) still develops even after sustained viral response (SVR) in patients with advanced liver fibrosis or cirrhosis. This meta-analysis investigated the predictive performance of transient elastography (TE) and fibrosis 4-index (FIB-4) for the development of HCC after SVR. Methods: We searched PubMed, MEDLINE, EMBASE, and the Cochrane Library for studies examining the predictive performance of these tests in adult patients with HCV. Two authors independently screened the studies' methodological quality and extracted data. Pooled estimates of sensitivity, specificity, and area under the curve (AUC) were calculated for HCC development using random-effects bivariate logit normal and linear-mixed effect models. Results: We included 27 studies (169,911 patients). Meta-analysis of HCC after SVR was possible in nine TE and 15 FIB-4 studies. Regarding the prediction of HCC development after SVR, the pooled AUCs of pre-treatment TE >9.2-13 kPa and FIB-4 >3.25 were 0.79 and 0.73, respectively. TE >8.4-11 kPa and FIB-4 >3.25 measured after SVR, maintained good predictive performance, albeit slightly reduced (pooled AUCs: 0.77 and 0.70, respectively). The identified optimal cut-off value for HCC development after SVR was 12.6 kPa for pre-treatment TE. That of TE measured after the SVR was 11.2 kPa. Conclusion: TE and FIB-4 showed acceptable predictive performance for HCC development in patients with HCV who achieved SVR, underscoring their utility in clinical practice for guiding surveillance strategies. Future studies are needed to validate these findings prospectively and validate their clinical impact.

Standardization of an antimicrobial resistance surveillance network through data management.

Introduction: The rapid spread of COVID-19 worldwide within 2 months demonstrated the vulnerability of the world's population to infectious diseases. In 2015, the Global Antimicrobial Resistance and Use Surveillance System (GLASS) was launched to combat antimicrobial resistance (AMR). However, there has been no comprehensive assessment of the decade-long global battle against AMR based on GLASS data. Methods: South Korea established Kor-GLASS (Korean-GLASS) to proactively monitor data quality and enable international collaborations. A unique feature of Kor-GLASS is the quality control center (QCC), which uses network hubs and ensures standardized, high-quality data through interlaboratory proficiency testing (IPT) and external quality assessment (EQA). In addition, the QCC multifaceted endeavors for integrated data quality management. Results: Since 2020, high-quality AMR data have indicated fluctuating antibiotic resistance rates in South Korea. This trend does not align with the decrease in antibiotic usage seen in humans but coincides with non-human antibiotic sales, indicating a need for greater monitoring of non-human antibiotic resistance. Comprehensive and robust management taking account of the intricate interplay among humans, animals, and the environment is essential. Kor-GLASS has been expanded into a "One Health" multiagency collaborative initiative. Discussion: Although a standardized solution is not suitable for all countries, it must align with the local context and international standards. A centralized top-down management structure such as that of the QCC is essential to ensure continuous data quality coordination. Sustained efforts and surveillance systems are crucial for monitoring and managing AMR and safeguarding human health.

Licochalcone A attenuates NMDA-induced neurotoxicity.

This study investigates the effect of Licochalcone A (Lico-A), a flavonoid from licorice roots known for its anti-inflammatory, anti-cancer, and antioxidant properties, on NMDA-induced neurotoxicity in primary cultured rat hippocampal neurons. The study measured cell survival following NMDA and Lico-A exposure, revealing that Lico-A at a 2.5 µg/ml significantly improved cell viability, countering the detrimental effects of NMDA. The study also analyzed synaptic changes by examining both postsynaptic density 95 (PSD95) and synaptophysin-targeted imaging, showing that Lico-A treatment resulted in a significant increase in synaptic puncta, contrasting with the reduction observed under NMDA exposure. Furthermore, levels of phosphorylated mixed lineage kinase domain-like pseudokinase (P-MLKL) and phosphorylated receptor-interacting serine/threonine-protein kinase 3 (P-RIP3), key necroptosis regulators, were measured using Western blotting. The results showed an increase in P-MLKL and P-RIP3 in neurons exposed to NMDA, which was reduced following Lico-A treatment. The response of astrocyte and microglia was also evaluated by immunostaining for glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule 1 (IBA-1) and tumor necrosis factor alpha (TNF-α). These markers exhibited heightened expression in the NMDA group, which was substantially reduced by Lico-A treatment. These findings suggest that Lico-A has neuroprotective effects against NMDA-induced neurotoxicity, potentially contributing to synaptic preservation, inhibition of neuronal necroptosis, and modulation of glial activation. Therefore, Lico-A shows promise as a neuroprotective agent for conditions associated with NMDA-related neurotoxicity.

Augmentation of intracranial self-stimulation induced by amphetamine-like drugs in Period circadian regulator 2 knockout mice is associated with intracellular Ca2+ levels.

Over the past decade, new psychoactive substances (NPS) have emerged in the illegal drug market and have continued to attract attention from the international community. Among these, amphetamine-like NPS, classified as stimulants, constitute a significant proportion. However, the pharmacological characteristics and mechanisms underlying addiction to amphetamine-like NPS remain poorly understood. Given that circadian rhythms are linked to the brain stimulation effects of methamphetamine (METH) and amphetamine, we investigated the effects of METH, 1-(4-methoxyphenyl)-N-methylpropan-2-amine (PMMA), and 1-(benzofuran-5-yl)-N-ethylpropan-2-amine (5-EAPB) on intracranial self-stimulation (ICSS) in wild-type (WT) or Period circadian regulator 2 knockout mice. Amphetamine-like drugs increase intracellular Ca2+ levels to provoke dopamine release, so we examined the impact of Per2 knockdown on intracellular Ca2+ levels in PC12 cells to elucidate a potential mechanism underlying NPS-induced ICSS enhancement. Our ICSS results showed that METH and PMMA significantly increased brain stimulation in Per2 knockout mice compared to WT mice. Similarly, METH and PMMA induced higher Ca2+ fluorescence intensity in Per2 knockdown PC12 cells than in control cells. In contrast, 5-EAPB did not produce significant changes in either ICSS or Ca2+ signaling. These findings suggest that Per2 plays a crucial role in the brain stimulation effects of amphetamine-like drugs through the regulation of intracellular Ca2+.