Search

Prunus cerasoides (PC) has been reported to have antimicrobial and anti-inflammatory properties, but its potential as a neuroprotective agent in a mouse model of cerebral ischemia has not been explored. Considering neuroglobin (Ngb), an endogenous neuroprotective factor, as a novel approach to neuroprotection, in this study, Ngb promoter activity, Ngb expression changes, and antioxidant protection by PC extract (PCE) and PC component compounds (PCCs) were analyzed in oxygen–glucose deprivation (OGD)-treated neurons. In vivo analysis involved transient middle cerebral artery occlusion (tMCAO) in mice with pre- and post-treatment exposure to PCE. Following ischemic stroke induction, neurological behavior scores were obtained, and cellular function-related signals were evaluated in the ischemic infarct areas. In addition to PCE, certain component compounds from PCE also significantly increased Ngb levels and attenuated the intracellular ROS production and cytotoxicity seen with OGD in primary neurons. Administration of PCE reduced the infarct volume and improved neurological deficit scores in ischemic stroke mice compared with the vehicle treatment. Increased Ngb levels in infarct penumbra with PCE treatment were also accompanied by decreased markers of apoptosis (activated p38 and cleaved caspase-3). Our findings point to the benefits of Ngb-mediated neuroprotection via PCE and its antioxidant activity in an ischemic stroke model.

Zinc plays a pivotal role in the function of cells and can induce apoptosis in various cancer cells, including Raji B lymphoma. However, the metabolic mechanism of Zn-induced apoptosis in Raji cells has not been explored. In this study, we performed global metabolic profiling using UPLC−Orbitrap−MS to assess the apoptosis of Raji cells induced by Zn ions released from ZnO nanorods. Multivariate analysis and database searches identified altered metabolites. Furthermore, the differences in the phosphorylation of 1380 proteins were also evaluated by Full Moon kinase array to discover the protein associated Zn−induced apoptosis. From the results, a prominent increase in glycerophosphocholine and fatty acids was observed after Zn ion treatment, but only arachidonic acid was shown to induce apoptosis. The kinase array revealed that the phosphorylation of p53, GTPase activation protein, CaMK2a, PPAR−γ, and PLA−2 was changed. From the pathway analysis, metabolic changes showed earlier onset than protein signaling, which were related to choline metabolism. LC−MS analysis was used to quantify the intracellular choline concentration, which decreased after Zn treatment, which may be related to the choline consumption required to produce choline-containing metabolites. Overall, we found that choline metabolism plays an important role in Zn-induced Raji cell apoptosis.

This case report discusses a patient diagnosed with L1 burst fracture, right lateral femoral condyle and proximal tibial and fibular head and neck comminuted fractures, and left medial femoral condyle and suspected tibial fractures after a traffic accident. She received integrated Korean medicine treatment, including motion- style acupuncture treatment (MSAT), electroacupuncture, acupuncture, herbal medicine, moxibustion, and cupping therapy for 112 days. The scores improved for the low back pain Numeric Rating Scale (NRS) (from 7 to 3), Oswestry Disability Index (from 94 to 38), bilateral leg pain NRS (from 6 to 2), Lysholm Knee Scoring Scale (from 0 to 66), left ankle manual muscle test (from Poor− to Normal), Korean version of the modified Barthel index (from 32 to 92), and EuroQol 5-dimension 5-level (from 25 to 9), as did mobility. Radiological scans also showed fracture healing. This study suggests the potential of MSAT in high-energy polytrauma care, particularly for fractures.

Background: Lung cancer has the highest mortality rate of all cancers worldwide. Conserving the immune system and reducing the adverse events associated with cancer treatment have become increasingly important. Our study aimed to investigate the immunological effects of herbal medicine (HM) alone, independent of conventional cancer therapies, in patients with non-small cell lung cancer (NSCLC). Methods: We searched 8 databases for articles published until March 2023. Bias risk was assessed using RevMan 5.4. Meta-analyses of CD4+ and CD8+ levels reported in the included RCTs were also performed. Results: A total of 610 patients from 5 RCTs were included in the analysis. Immune markers in the peripheral blood of patients treated with HM alone were compared with those in the control group. As a result of meta-analyses, CD4+ (three studies; mean difference(MD) = 5.21, 95 confidence interval (CI) [3.26, 7.27], I 2 = 61%, n = 428) and CD4+/CD8+ (two studies; MD = 0.22, 95% CI [0.18, 0.26], I 2 = 0%, n = 278) significantly increased in the treatment group, while CD8+ levels (three studies; MD = −3.04, 95% CI [−5.80, −0.29], I 2 = 74%, n = 428) decreased in HM groups compared to comparison groups. In a single trial, IL-1, IL-6, tumor necrosis factor (TNF)-a levels and the number of Tregs in the treatment group significantly decreased, while Th17 levels and the Th17/Treg ratios increased. Conclusion: This study provides a comprehensive and systematic review of the immunological effects of HM in patients with NSCLC. Future studies should explore how the immunological effects of HM correlate with clinical outcomes, such as tumor response and survival rates. PROSPERO registration: CRD42023459

BackgroundDespite the increasing popularity of Korean Medicine (KM), its scientific evidence faces scrutiny. Instead of randomized controlled trials, registries are favored to capture the real world of KM practice due to the difficulties associated with proper control and the holistic nature of the KM approach. This review aimed to examine the KM registries in detail, identify the scope and focus of studies within this field, and assess the research trends.MethodsWe conducted a comprehensive analysis of KM registries listed in trial registration platforms, covering records from their inception until the end of 2023. The selection criteria aimed to include studies focusing on various interventions related to KM, with data extraction focusing on study characteristics and outcomes measured. The analysis utilized descriptive statistics to summarize the findings.ResultsWe identified a steady increase in registry studies (2015, one; 2023, seven). Musculoskeletal disorders were most studied (28%), aligning with patients’ demand. The involvement of 112 primary clinics and Quality of Life (QOL) as the predominant outcome in 14 (66.7%) registries demonstrates the positive impact on patient well-being and the critical role that primary clinics play in KM practice.ConclusionOur findings indicate a heightened interest and commitment to evidence-based KM practices. Future Registries should be implemented on a large scale, incorporating long-term follow-up encompassing primary clinics. This approach would enable a comprehensive evaluation of the effectiveness and safety of KM interventions, as well as offer valuable insights into the influence of KM on chronic conditions and QOL.

Background: Lung cancer, especially non-small cell lung cancer (NSCLC), poses a significant health challenge globally due to its high mortality. Afatinib, a second-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has shown superior efficacy over traditional chemotherapy in NSCLC treatment. However, issues like secondary resistance and adverse effects call for alternative therapies. HAD-B1, comprising 4 herbal medicines, has shown promise in lung cancer treatment in both preclinical and clinical settings. This study assesses the combination of HAD-B1 and Afatinib in advanced NSCLC patients to potentially improve outcomes by addressing the limitations of current EGFR-TKI therapies. Method: A randomized, open-label trial evaluated the efficacy and safety of HAD-B1 with Afatinib in 90 EGFR-mutation-positive NSCLC patients. Participants were divided into treatment and control groups, receiving Afatinib with or without HAD-B1. The study focused on the initial dose maintenance rate and disease control rate (DCR) of Afatinib, alongside secondary outcomes like survival rates and quality of life, under continuous safety monitoring. Results: Among the 90 participants, no significant difference was found in initial dose maintenance (60.98% in the treatment group vs 52.50% in the control, P = .4414) or DCR (80.49% vs 90.00%, P = .2283). Secondary outcomes like PFS, TTP, and OS showed no notable differences. However, physical functioning significantly improved in the treatment group ( P = .0475, PPS group). The control group experienced higher rates of adverse events of special interest and adverse drug reactions ( P = .01), suggesting HAD-B1 with Afatinib might enhance physical function without increasing adverse effects. Conclusion: Combining HAD-B1 with Afatinib potentially improves quality of life and reduces adverse events in advanced NSCLC patients. Further research is necessary to confirm the long-term benefits of this combination therapy, aiming to advance NSCLC treatment outcomes. Trial registration: Clinical Research Information Service (CRIS) of the Republic of Korea, https://cris.nih.go.kr/ (ID: KCT0005414).

This paper demonstrates the significance of employing the infinitesimal dipole modeling (IDM) in analyzing uniform circular array-orbital angular momentum (UCA-OAM) near-fields in terms of electromagnetic (EM) energy densities. The electric and magnetic field, and the EM energy densities of UCA-OAM waves are theoretically analyzed and numerically estimated where the spatial distribution of EM Lagrangian density and complex Helicity is visualized. It is validated that the IDM is more accurate than the conventional far-field assumption in evaluating the near-fields of UCA-OAM waves as the EM Lagrangian density and the complex Helicity are clearly depicted based on the IDM, while they are unobservable with the far-field assumption. The visualization of EM Lagrangian density and complex Helicity can be beneficial in designing UCA-OAM communication system as it suggests the mutual coupling between antennas by describing the regions of reactive EM energy densities and non-orthogonal EM fields in the near-field region.

This paper proposes a new measurement method for mobile antennas, balancing accuracy and efficiency by applying magnetic infinitesimal dipole source reconstruction. It introduces a model of the antenna as magnetic infinitesimal dipoles and derives an equation for the spherical near and far electric field. Existing methods require 595 to 7381 measurement points, but the proposed method satisfies fairly good accuracy with 64 points limited to a closed antenna. Validated through simulations and measurements, the method is limited to mobile antennas, particularly effective for closed structures, as demonstrated with over 99% pattern correlation in simulations for inverted-F and patch array antennas. For open structures such as horn antennas, the proposed method cannot be used as it has a pattern correlation of 80%.

IntroductionFacial palsy (FP) significantly affects the quality of life of patients and poses a treatment challenge in primary healthcare settings. This study aimed to develop a Korean medicine (KM) core outcome set (COS) for FP, with a focus on evaluating the effectiveness of herbal medicine (HM) treatments in KM primary clinics.MethodsOutcomes and effect modifiers related to FP treatments were initially identified through related review articles. Subsequently, experts in the field took part in three rounds of modified Delphi consensus exercises to refine and prioritize these outcomes and effect modifiers. Additionally, primary KM clinicians were involved in a Delphi consensus round to assess the suitability and feasibility of the proposed COS in real-world clinical settings.ResultsThe initial review of related literature identified 44 relevant studies, resulting in an initial selection of 23 outcomes and 10 effect modifiers. The expert consensus process refined these to 8 key outcomes and 6 effect modifiers, which established the foundation of the COS-FP-KM. Subsequently, primary KM clinicians confirmed the practicality and applicability of the COS, endorsing its suitability for use in KM primary clinics.ConclusionThe COS-FP-KM establishes a standardized approach for assessing HM treatment effectiveness in FP patients in KM primary clinics. The COS-FP-KM encourages consistent outcome reporting and enhances patient care quality. Future work should aim to integrate broader stakeholder perspectives to refine and validate the COS further.

Broadly-neutralizing antibodies (bNAbs) against HIV-1 Env can protect from infection. We characterize Ab1303 and Ab1573, heterologously-neutralizing CD4-binding site (CD4bs) antibodies, isolated from sequentially-immunized macaques. Ab1303/Ab1573 binding is observed only when Env trimers are not constrained in the closed, prefusion conformation. Fab-Env cryo-EM structures show that both antibodies recognize the CD4bs on Env trimer with an 'occluded-open' conformation between closed, as targeted by bNAbs, and fully-open, as recognized by CD4. The occluded-open Env trimer conformation includes outwardly-rotated gp120 subunits, but unlike CD4-bound Envs, does not exhibit V1V2 displacement, 4-stranded gp120 bridging sheet, or co-receptor binding site exposure. Inter-protomer distances within trimers measured by double electron-electron resonance spectroscopy suggest an equilibrium between occluded-open and closed Env conformations, consistent with Ab1303/Ab1573 binding stabilizing an existing conformation. Studies of Ab1303/Ab1573 demonstrate that CD4bs neutralizing antibodies that bind open Env trimers can be raised by immunization, thereby informing immunogen design and antibody therapeutic efforts.

Assisted reproduction technology (ART) procedures are often impacted by post-ovulatory aging (POA), which can lead to reduced fertilization rates and impaired embryo development. This study used RNA sequencing analysis and experimental validation to study the similarities and differences between in vivo- and vitro-matured porcine oocytes before and after POA. Differentially expressed genes (DEGs) between fresh in vivo-matured oocyte (F_vivo) and aged in vivo-matured oocyte (A_vivo) and DEGs between fresh in vitro-matured oocyte (F_vitro) and aged in vitro-matured oocyte (A_vitro) were intersected to explore the co-effects of POA. It was found that “organelles”, especially “mitochondria”, were significantly enriched Gene Ontology (GO) terms. The expression of genes related to the “electron transport chain” and “cell redox homeostasis” pathways related to mitochondrial function significantly showed low expression patterns in both A_vivo and A_vitro groups. Weighted correlation network analysis was carried out to explore gene expression modules specific to A_vivo. Trait–module association analysis showed that the red modules were most associated with in vivo aging. There are 959 genes in the red module, mainly enriched in “RNA binding”, “mRNA metabolic process”, etc., as well as in GO terms, and “spliceosome” and “nucleotide excision repair” pathways. DNAJC7, IK, and DDX18 were at the hub of the gene regulatory network. Subsequently, the functions of DDX18 and DNAJC7 were verified by knocking down their expression at the germinal vesicle (GV) and Metaphase II (MII) stages, respectively. Knockdown at the GV stage caused cell cycle disorders and increase the rate of abnormal spindle. Knockdown at the MII stage resulted in the inefficiency of the antioxidant melatonin, increasing the level of intracellular oxidative stress, and in mitochondrial dysfunction. In summary, POA affects the organelle function of oocytes. A_vivo oocytes have some unique gene expression patterns. These genes may be potential anti-aging targets. This study provides a better understanding of the detailed mechanism of POA and potential strategies for improving the success rates of assisted reproductive technologies in pigs and other mammalian species.

Background: Gastric cancer is a common cause of global mortality, with significant challenges during treatment due to side effects and complications. Traditional herbal medicine (THM) has emerged as a potential adjuvant therapy to enhance cancer treatment by reducing side effects and bolstering the immune response. This study conducted a meta-analysis to assess the efficacy and safety of THM as an adjuvant therapy in post-surgical gastric cancer patients. Methods: PubMed, Cochrane Library, EMBASE, CNKI, CiNii, KMBASE, KISS, OASIS, RISS, and ScienceON databases were searched from inception through December, 2021. The outcomes considered in this analysis encompassed tumor response, quality of life (QoL), side effects, and tumor markers. Additionally, a frequency analysis of the most commonly used herbs in the included studies was conducted. A total of 36 randomized controlled trials (RCTs) were included, and data were extracted according to study design. The analysis compared groups receiving chemotherapy alone with those receiving both chemotherapy and THM treatment. Results: The group receiving both chemotherapy and THM showed substantial improvement in tumor response compared to the chemotherapy-only control group (RR 1.25, 95% CI [1.09, 1.45]). QoL also significantly increased in the THM-treated group. Most drug adverse reactions displayed statistical significance, except for platelet reduction. Tumor markers CEA, CA19-9, and CA72-4 exhibited significant improvements, but CA125 did not. The 1, 2, and 3-year survival rates improved, with RR values of 1.08 (95% CI [1.02, 1.14]), 1.32 (95% CI [1.19, 1.47]), and 1.42 (95% CI [1.12, 1.79]) respectively. However, some publication bias was indicated. Conclusion: THM may offer potential benefits as a complementary approach to post-surgical anticancer therapy in gastric cancer patients. Improved tumor response, quality of life, and survival rates were reported. However, it is important to exercise caution due to the possibility of publication bias, and further research is needed to confirm these findings. Registration:PROSPERO CRD 42022354133

Among the family of GPCR kinases (GRKs) that regulate receptor phosphorylation and signaling termination, G-protein-coupled receptor kinase 2 (GRK2) binds to HSP90 in response to hypoxia or other stresses. In this study, we investigated the effects of GRK2 knockdown and inhibition on porcine embryonic development from the zygote stage. Immunofluorescence and western blotting were used to determine the localization and expression, respectively, of GRK2 and related proteins. First, GRK2 and p-GRK2 were expressed in both the cytoplasm and membrane and co-localized with HSP90 on the membrane. The mRNA level of GRK2 increased until the 8C-morula stage, suggesting that GRK2 may play an essential role during the early development of the porcine embryos. GRK2 knockdown reduced porcine embryo development capacity and led to significantly decreased blastocyst quality. In addition, inhibition of GRK2 also induced poor ability of embryo development at an early stage, indicating that GRK2 is critical for embryonic cleavage in pigs. Knockdown and inhibition of GRK2 reduced HSP90 expression, AKT activation, and cAMP levels. Additionally, GRK2 deficiency increased LC3 expression, suggesting enhanced autophagy during embryo development. In summary, we showed that GRK2 binds to HSP90 on the membrane to regulate embryonic cleavage and AKT activation during embryonic development in pigs. [ABSTRACT FROM AUTHOR]

HIV-1 Envelope (Env) mediates viral-host membrane fusion after binding host-receptor CD4 and coreceptor. Soluble envelopes (SOSIPs), designed to mimic prefusion conformational states of virion-bound envelopes, are proposed immunogens for eliciting neutralizing antibodies, yet only static structures are available. To evaluate conformational landscapes of ligand-free, CD4-bound, inhibitor-bound, and antibody-bound SOSIPs, we measured inter-subunit distances throughout spin-labeled SOSIPs using double electron-electron resonance (DEER) spectroscopy and compared results to soluble and virion-bound Env structures, and single-molecule fluorescence resonance energy transfer (smFRET)-derived dynamics of virion-bound Envs. Unliganded SOSIP measurements were consistent with closed, neutralizing antibody-bound structures and shielding of non-neutralizing epitopes, demonstrating homogeneity at Env apex, increased flexibility near Env base, and no evidence for the intra-subunit flexibility near Env apex suggested by smFRET. CD4 binding increased inter-subunit distances and heterogeneity, consistent with rearrangements required for coreceptor binding. Results suggest similarities between SOSIPs and virion-bound Envs and demonstrate DEER's relevance for immunogen design.

The coronavirus disease 2019 (COVID-19) pandemic presents an urgent health crisis. Human neutralizing antibodies that target the host ACE2 receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein.sup.1-5 show promise therapeutically and are being evaluated clinically.sup.6-8. Here, to identify the structural correlates of SARS-CoV-2 neutralization, we solved eight new structures of distinct COVID-19 human neutralizing antibodies.sup.5 in complex with the SARS-CoV-2 spike trimer or RBD. Structural comparisons allowed us to classify the antibodies into categories: (1) neutralizing antibodies encoded by the VH3-53 gene segment with short CDRH3 loops that block ACE2 and bind only to 'up' RBDs; (2) ACE2-blocking neutralizing antibodies that bind both up and 'down' RBDs and can contact adjacent RBDs; (3) neutralizing antibodies that bind outside the ACE2 site and recognize both up and down RBDs; and (4) previously described antibodies that do not block ACE2 and bind only to up RBDs.sup.9. Class 2 contained four neutralizing antibodies with epitopes that bridged RBDs, including a VH3-53 antibody that used a long CDRH3 with a hydrophobic tip to bridge between adjacent down RBDs, thereby locking the spike into a closed conformation. Epitope and paratope mapping revealed few interactions with host-derived N-glycans and minor contributions of antibody somatic hypermutations to epitope contacts. Affinity measurements and mapping of naturally occurring and in vitro-selected spike mutants in 3D provided insight into the potential for SARS-CoV-2 to escape from antibodies elicited during infection or delivered therapeutically. These classifications and structural analyses provide rules for assigning current and future human RBD-targeting antibodies into classes, evaluating avidity effects and suggesting combinations for clinical use, and provide insight into immune responses against SARS-CoV-2. Eight structures of human neutralizing antibodies that target the SARS-CoV-2 spike receptor-binding domain are reported and classified into four categories, suggesting combinations for clinical use., Author(s): Christopher O. Barnes [sup.1] , Claudia A. Jette [sup.1] , Morgan E. Abernathy [sup.1] , Kim-Marie A. Dam [sup.1] , Shannon R. Esswein [sup.1] , Harry B. Gristick [sup.1] [...]