Molecular Mechanisms of Anticarcinogenic Potential of Hydrocotyle umbellata and Its Major Components.

Despite the development of several anticancer treatments, there remains a need for new drugs that can overcome resistance and reduce side effects. While the medicinal herb Hydrocotyle umbellata (H. umbellata) has been used to relieve pain and inflammation, its antitumor properties have not yet been explored. In this study, we investigated the anticarcinogenic potential of H. umbellata extract (HUE) and its major components, as well as the underlying molecular mechanisms. Our results showed that HUE inhibited the growth of various tumor cell lines, including B16F10, without affecting non-cancer cells. Furthermore, HUE was effective in treating and preventing tumor growth in mice. Our mechanistic studies revealed that HUE inhibited cellular respiration, thereby reducing tumor cell proliferation. When combined with 2-deoxy-D-glucose, HUE demonstrated an enhanced anticancer effect by increasing the rate apoptosis. Analysis of the ethyl acetate and n-butanol fractions of HUE identified 1,3,4-trihydroxy-2-butanyl-α-d-glucopyranoside and caffeoylquinic acid derivatives as the major components responsible for the observed anticancer effects. In conclusion, our findings suggest that HUE and its two major components have the potential to be developed as effective therapeutic agents for a wide range of tumors by targeting cancer cell metabolism.

Tixagevimab/cilgavimab (AZD7442/Evusheld) prevent from COVID19 in patients with hematologic malignancies under active chemotherapy.

Despite the efficacy of COVID-19 vaccines, patients with hematologic malignancy may still be fatal from COVID19. Therefore, we prospectively performed the analysis of administration of tixagevimab/cilgavimab in the real-world. In August 2022, 94 patients under active chemotherapy for lymphoma, multiple myeloma, or acute leukemia received a single dose AZD7442/Evusheld (two consecutive intramuscular injections of tixagevimab and cilgavimab, 300 mg each). Quantitative measurement of anti-SARS-CoV-2 spike protein (anti-S) and viral nucleocapsid (anti-N) titers were conducted before administration of tixagevimab/cilgavimab and at 1, 3, and 6 months after administration. Twenty-five patients (26.6%) had previously confirmed COVID-19 infection. Fifty-eight patients (61.7%) had previously received COVID-19 vaccinations, with a median of two doses (range, 1-5). The median anti-S Ab level increased from baseline (997.05 AU/mL) to 1 month (20,967.25 AU/mL), then decreased at 3 months (13,145.0 AU/mL), and 6 months (7123.0 AU/mL) (p < 0.001). There was no significant safety issue with tixagevimab/cilgavimab. With a median follow-up time of 6 months, thirteen patients (13.8%) had documented SARS-Cov-2 infection. A 20.2% rate of anti-N positivity was observed six months after the administration of tixagevimab/cilgavimab. The results of this study support the potential role of tixagevimab/cilgavimab for the prevention of symptomatic and severe COVID-19.Trial registration: KCT0007617; August 16, 2022.

Ischemia-modified albumin: a novel blood marker of endoscopic mucosal healing in inflammatory bowel disease.

BACKGROUND/AIMS: The achievement of endoscopic remission is an important therapeutic goal in the treatment of inflammatory bowel diseases (IBD). We aimed to evaluate the role of fecal calprotectin (FCP) and ischemia-modified albumin (IMA) as biomarkers for evaluating IBD disease activity. METHODS: A total of 48 patients with IBD (20 with ulcerative colitis and 28 with Crohn's disease) were included in this study. FCP and serum C-reactive protein levels, erythrocyte sedimentation rate, and IMA were measured in patients with IBD and compared with endoscopic findings. RESULTS: Elevated FCP and serum IMA levels were significantly associated with endoscopic non-mucosal healing. The correlation between FCP and IMA was not significant. Analysis of the receiver operating characteristic curve showed that both FCP and IMA had diagnostic value in predicting non-mucosal healing. When the Ln(FCP)+IMA/10 value was calculated using both factors, the predictive value for non-mucosal healing increased; however, no significant difference was observed. CONCLUSIONS: IMA could be a candidate serum biomarker for predicting endoscopic mucosal healing in IBD.

Risk factors of menopause after allogeneic hematopoietic cell transplantation in premenopausal adult women.

OBJECTIVES: Allogeneic hematopoietic stem-cell transplantation (HCT) is the only curative option for most hematologic malignancies. However, HSCT can cause early menopause and various complications in premenopausal women. Therefore, we aimed to investigate risk factors predicting early menopause and its clinical implications among survivors post HCT. METHODS: We retrospectively analyzed 30 adult women who had received HCT at premenopausal status between 2015 and 2018. We excluded patients who had received autologous stem cell transplantation, had relapsed, or died of any cause within 2 years of HCT. RESULTS: The median age at HCT was 41.6 years (range, 22-53). Post-HCT menopause was identified in 90% of myeloablative conditioning (MAC) HCT and 55% of reduced-intensity conditioning (RIC) HCT (p = .101). In the multivariate analysis, the post-HCT menopausal risk was 21 times higher in a MAC regimen containing 4 days of busulfan (p = .016) and 9.3 times higher in RIC regimens containing 2-3 days of busulfan (p = .033) than that of non-busulfan-based conditioning regimens. CONCLUSIONS: Higher busulfan dose in conditioning regimens is the most significant risk factor affecting post-HCT early menopause. Considering our data, we need to decide on conditioning regimens and individualized fertility counseling before HCT for premenopausal women.

T-large granular lymphocytic leukemia.

T-cell large granular lymphocyte (T-LGL) leukemia is characterized by clonal expansion of cytotoxic T cells resulting in cytopenia. The proliferation of clonal LGLs is caused by prolonged antigenic stimulation, which leads to apoptotic dysregulation owing mainly to the constitutive activation of survival pathways, notably the JAK/STAT pathway. Understanding how leukemic T-LGL persists can aid in the development of future immunosuppressive therapies. In this review, we summarize the diagnosis and current standard of therapy for T-LGL leukemia, as well as recent advances in clinical trials.

Plasmacytoid dendritic cell neoplasms.

Plasmacytoid dendritic cells (pDCs) are type I interferon-producing cells that modulate immune responses. There are two types of pDC neoplasms: 1) mature pDC proliferation (MPDCP) associated with myeloid neoplasm and 2) blastic pDC neoplasm (BPDCN). MPDCP is a clonal expansion of mature pDCs that is predominantly associated with chronic myelomonocytic leukemia. In contrast, BPDCN is a clinically aggressive myeloid malignancy involving the skin, bone marrow, lymphatic organs, and central nervous system. There are various types of skin lesions, ranging from solitary brown or violaceous to disseminated cutaneous lesions, which often spread throughout the body. The expression of CD4, CD56, CD123, and pDC markers (TCL-1, TCF4, CD303, and CD304, etc.) are typical immunophenotype of BPDCN. Historically, BPDCN treatment has been based on acute leukemia regimens and allogeneic hematopoietic cell transplantation in selected patients. Recent advances in molecular biology and genetics have led to the development of targeted agents, such as tagraxofusp (a recombinant fusion protein targeting CD123), anti-CD123 CAR-T cells, XmAb14045, and IMGN632. Lastly, this review provides a comprehensive overview of pDC neoplasms.

Performance Validation of Three Scoring Systems for the Prediction of Thrombotic Microangiopathy Due to Severe ADAMTS13 Deficiency and the Response to Therapeutic Plasma Exchange: First Study in Korea.

Background: The BENTLEY score (B-S), French thrombotic microangiopathy (TMA) Reference Center score (FTMA-S), and PLASMIC score (PLASMIC-S) have been developed for TMA diagnostic prediction. We retrospectively validated their predictive performances in patients with severe (<10%) disintegrin and metalloprotease with thrombospondin type 1 motif, member 13 (ADAMTS13) deficiency in terms of the risk of TMA and response to therapeutic plasma exchange (TPE). Methods: The predictive performances of the three scoring systems were compared in 145 patients with suspected TMA who underwent ADAMTS13 activity tests between January 2014 and September 2022. The response to TPE and mortality in TMA-positive patients were compared after risk stratification, using the Mann-Whitney U and Fisher's exact tests. Results: The PLASMIC-S, FTMA-S, and B-S showed area under the curve values of 0.820, 0.636, and 0.513, respectively, for predicting TMA positivity in high-risk patients. The PLASMIC-S showed higher sensitivity (81.8%), negative predictive value (91.2%), positive predictive value (PPV; 66.7%), and accuracy (82.1%) than the FTMA-S (72.7%, 82.1%, 41.0%, and 60.0%, respectively) and B-S (4.6%, 70.2%, 50.0%, and 69.7%, respectively). The PLASMIC-S also showed higher specificity than the FTMA-S (82.2% vs. 54.5%). The modified PLASMIC-S, including lactate dehydrogenase/upper limit of normal ratios, increased the specificity, PPV, and accuracy to 97.0%, 92.3%, and 92.4%, respectively. In TMA-positive patients, high risk assessed by the PLASMIC-S predicted higher platelet recovery rates and less TPE sessions required for recovery than for those assessed at low-to-intermediate risk. Conclusions: PLASMIC-S is the preferred scoring system for detecting patients with TMA positivity and for prognosis before confirmation of ADAMTS13 activity.

Research use only and cell population data items obtained from the Beckman Coulter DxH800 automated hematology analyzer are useful in discriminating MDS patients from those with cytopenia without MDS.

We investigated the performance of research use only/cell population data (RUO/CPD) items obtained from the Beckman Coulter DxH800 automated hematologic analyzer in discriminating MDS patients from cytopenic patients without MDS.Total of 14 routine CBC, 18 research use only (RUO) items, and 70 CPD items were obtained retrospectively at diagnosis. The results were then compared between 94 MDS patients and 100 cytopenic patients without MDS. In items with statistically significant differences, receiver operating characteristic (ROC) analysis was performed and the results were compared.Four CBC/RUO items [red cell distribution width-standard deviation (RDW-SD), immature reticulocyte fraction (IRF), mean sphered cell volume (MSCV), high light scatter reticulocytes (HLR)], and two CPD items [mean volume of neutrophils (NE-V-Mean) and mean volume of early granulated cells (EGC-V-Mean)] showed area-under the curve (AUC) scores > 0.750. Notably, four RUO/CPD items (MSCV > 81.4/HLR > 0.15%/NE-V-Mean > 145/EGC-V-Mean > 156) showed high sensitivity (91.9%/93.6%/88.1%/90.2%, respectively) in discriminating MDS patients from cytopenic patients without MDS. With these six items, scores ≥ 4 (defined as ≥ 4 items exceeding cutoff values out of six items) showed AUC scores/sensitivity/specificity/accuracy (0.891/87.3%/79.0%/83.0%, respectively).Six CBC/RUO/CPD items showed satisfactory AUC scores of > 0.750, and four RUO/CPD items showed high sensitivity in discriminating MDS patients from cytopenic patients without MDS. Scoring system with six items showed high sensitivity, specificity, and accuracy with decision criteria of ≥ 4 scores. Therefore, DxH800 RUO/CPD items would be useful in discriminating MDS patients from cytopenic patients without MDS.

Effect of changes in lymphocyte subsets at diagnosis in acute myeloid leukemia on prognosis: association with complete remission rates and relapse free survivals.

We prospectively investigated whether the characteristics of lymphocyte subsets at diagnosis in acute myeloid leukemia (AML) patients are different from healthy controls and affect treatment outcomes. A total of 91 AML patients classified into 3 genetic risk subgroups (favorable/intermediate/poor) according to 2022 NCCN guidelines were enrolled. We measured lymphocyte subsets by flow cytometry with peripheral blood samples at diagnosis and compared results with healthy controls. Influences of lymphocyte subsets on complete remission (CR) rates and survivals were also evaluated. AML patients had significantly lower numbers and proportions of CD56dimCD16+ natural killer (NK) cells, central memory T cells, and regulatory T cells than healthy controls. Higher proportion of helper/inducer T cells, CD4+CD31+ naïve T cells, and decreased proportion of NK cells significantly increased CR rates in 65 non-promyelocytic leukemia patients (P = 0.034, 0.027, and 0.019, respectively), and it was also significant in multivariable analysis with age/risk adjusted (P = 0.014, 0.016, and 0.045, respectively). NK cells < 4.8% of lymphocytes demonstrated significantly shorter relapse free survivals (RFS) in both univariate and multivariate analyses with risk adjusted (P = 0.006 and 0.037, respectively). AML patients showed significant lower numbers of CD56dimCD16+ NK cells, central memory T cells, and regulatory T cells than healthy controls at diagnosis. Higher proportion of helper/inducer T cells and CD4+CD31+ naïve T cells and decreased proportion of NK cells at diagnosis were independent factor of increasing probability of CR, and proportion of NK cells < 4.8% at diagnosis had adverse impact in RFS.

Terahertz radiation from propagating acoustic phonons based on deformation potential coupling.

We report on new THz electromagnetic emission mechanism from deformational coupling of acoustic (AC) phonons with electrons in the propagation medium of non-polar Si. The epicenters of the AC phonon pulses are the surface and interface of a GaP transducer layer whose thickness (d) is varied in nanoscale from 16 to 45 nm. The propagating AC pulses locally modulate the bandgap, which in turn generates a train of electric field pulses, inducing an abrupt drift motion at the depletion edge of Si. The fairly time-delayed THz bursts, centered at different times (t1T H z, t2T H z, and t3T H z), are concurrently emitted only when a series of AC pulses reach the point of the depletion edge of Si, even without any piezoelectricity. The analysis on the observed peak emission amplitudes is consistent with calculations based on the combined effects of mobile charge carrier density and AC-phonon-induced local deformation, which recapitulates the role of deformational potential coupling in THz wave emission in a formulatively distinct manner from piezoelectric counterpart.

The Role of the Graphene Oxide (GO) and Reduced Graphene Oxide (RGO) Intermediate Layer in CZTSSe Thin-Film Solar Cells.

Cu2ZnSn(S,Se)4 (CZTSSe) solar cells with low cost and eco-friendly characteristics are attractive as future sources of electricity generation, but low conversion efficiency remains an issue. To improve conversion efficiency, a method of inserting intermediate layers between the CZTSSe absorber film and the Mo back contact is used to suppress the formation of MoSe2 and decomposition of CZTSSe. Among the candidates for the intermediate layer, graphene oxide (GO) and reduced GO have excellent properties, including high-charge mobility and low processing cost. Depending on the type of GO, the solar cell parameters, such as fill factor (FF), were enhanced. Thus, the conversion efficiency of 6.3% was achieved using the chemically reduced GO intermediate layer with significantly improved FF.

Neutrophil-Selective Fluorescent Probe Development through Metabolism-Oriented Live-Cell Distinction.

Human neutrophils are the most abundant leukocytes and have been considered as the first line of defence in the innate immune system. Selective imaging of live neutrophils will facilitate the in situ study of neutrophils in infection or inflammation events as well as clinical diagnosis. However, small-molecule-based probes for the discrimination of live neutrophils among different granulocytes in human blood have yet to be reported. Herein, we report the first fluorescent probe NeutropG for the specific distinction and imaging of active neutrophils. The selective staining mechanism of NeutropG is elucidated as metabolism-oriented live-cell distinction (MOLD) through lipid droplet biogenesis with the help of ACSL and DGAT. Finally, NeutropG is applied to accurately quantify neutrophil levels in fresh blood samples by showing a high correlation with the current clinical method.

Histiocytic pleural effusion: the strong clue to malignancy.

BACKGROUND: There have been many studies on the clinical characteristics of neutrophilic, lymphocytic, and/or eosinophilic pleural effusion. While caring for patients with pleural effusion, we found that histiocytic pleural effusion (HisPE) was not uncommon. However, few studies have explored HisPE. The purpose of the present study was to determine the clinical characteristics and etiologies of HisPE. METHODS: In this retrospective study, HisPE was defined as pleural fluid white blood cells comprised of ≥ 50% histiocytes. Using a clinical data warehouse, patients with HisPE among all patients aged >18 years who underwent thoracentesis and pleural fluid analysis between January 2010 and December 2019 at Ulsan University Hospital were enrolled. A total of 295 (9.0%) of 3279 patients who underwent thoracentesis were identified as HisPE patients. Among them, 201 with exudative HisPE were included. Clinical characteristics and etiologies were extracted from medical records and analyzed. RESULTS: Among the 201 patients with exudative HisPE, the major causes were malignant pleural effusion (n = 102 [50.7%]), parapneumonic effusion (n = 9 [4.5%]), and tuberculous pleurisy (n = 9 [4.5%]). In the 102 patients with malignant pleural effusion, the main types of cancer were lung (n = 42 [41.2%]), breast (n = 16 [15.7%]), and stomach cancer (n = 11 [10.8%]). Among lung cancers, adenocarcinoma (n = 34 [81.0%]) was the most common histology. CONCLUSIONS: The leading cause of exudative HisPE was malignancy, particularly lung cancer. Physicians should consider the possibility of malignant disease if histiocytes are predominantly present in pleural effusion.

Late complications and quality of life assessment for survivors receiving allogeneic hematopoietic stem cell transplantation.

PURPOSE: The survival rates of patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) have improved. However, HSCT can induce significant long-term complications. Therefore, we investigated the late complications and risk factors for quality of life (QOL) post-HSCT. METHODS: We retrospectively analyzed 67 adult survivors over 2 years after HSCT between 2015 and 2018 at Ulsan University Hospital, Ulsan, Korea. The survey data including FACT-BMT, Hospital Anxiety and Depression Scale, and NCCN Distress Thermometer were collected as patient-reported outcomes using a tablet PC during a routine practice of survivorship clinic. RESULTS: The median age was 46 years. The most common symptom was fatigue (80.6%). Younger age (< 60 years), acute lymphoblastic leukemia (ALL), chronic graft-versus-host disease (GVHD), and immunosuppressant use were significantly associated with worse QOL and depression. Additionally, younger survivors (< 60 years) showed significantly more fatigue and anxiety compared with elderly survivors (≥ 60 years). Female sex was significantly associated with lower physical well-being and higher distress than male sex. CONCLUSION: Younger patients (< 60 years), female, ALL, chronic GVHD, and continuous immunosuppressant use were significant risk factors for worse QOL and depression. Hence, creating a more active survivorship care plan after HSCT, specifically for these patients, is required.

The Anti-Tumor Effects of Oenothera odorata Extract Are Mediated by Inhibition of Glycolysis and Cellular Respiration in Cancer Cells.

Cancer is caused by uncontrolled cell division and is a leading cause of mortality worldwide. Oenothera odorata (O. odorata) extract is used in herbal medicine to inhibit inflammation, but its potential anti-tumor properties have not been fully evaluated. Here, we demonstrated that O. odorata extract inhibits the proliferation of lung adenocarcinoma and melanoma cell lines In Vitro, and also inhibits the growth of melanoma cells In Vivo. After partitioning the extract with n-hexane, chloroform, ethyl acetate, and n-butanol, it was found that the butanol-soluble (OOB) and water-soluble (OOW) fractions of O. odorata extract are effective at inhibiting tumor cell growth In Vivo although OOW is more effective than OOB. Interestingly, these fractions did not inhibit the growth of non-cancerous cells. The anti-proliferative effects of the OOW fraction were found to be mediated by inhibition of glycolysis and cellular respiration. UPLC of both fractions showed two major common peaks, which were predicted to be hydrolyzable tannin-related compounds. Taken together, these data suggest that O. odorata extract has anti-tumor properties, and the molecular mechanism involves metabolic alterations and inhibition of cell proliferation. O. odorata extract therefore holds promise as a novel natural product for the treatment of cancer.

Treatment outcome and prognostic factors of Korean patients with chronic lymphocytic leukemia: a multicenter retrospective study.

BACKGROUND/AIMS: Compared with Western countries, chronic lymphocytic leukemia (CLL) rarely occurs in Asia and has different clinical characteristics. Thus, we aimed to evaluate the clinical characteristics, treatment outcomes, and prognostic significance of Korean patients with CLL. METHODS: We retrospectively analyzed 90 patients with CLL who had received chemotherapy at 6 centers in Korea between 2000 and 2012. RESULTS: Compared with Western patients with CLL, Korean patients with CLL express lambda (42.0%) and atypical markers such as CD22 and FMC7 (76.7% and 40.0%, respectively) more frequently. First-line chemotherapy regimens included chlorambucil (n = 43), fludarabine and cyclophosphamide (FC) (n = 20), fludarabine (n = 13), rituximab-FC (n = 4). The remaining patients were treated with other various regimens (n = 10). The 5-year overall survival (OS) and progression-free survival (PFS) rates were 79.3% and 28.1%, respectively. Multivariate analyses showed that hyperleukocytosis (≥ 100 × 103/µL), extranodal involvement, and the Binet C stage were significant negative prognostic factors for OS (hazard ratio [HR] 4.75, p = 0.039; HR 21.6, p = 0.002; and HR 4.35, p = 0.034, respectively). Cytogenetic abnormalities including complex karyotypes (≥ 3), del(11q), and del(17) had a significantly adverse impact on both OS and PFS (p < 0.001 and p = 0.010, respectively). CONCLUSION: Initial hyperleukocytosis, extranodal involvement, complex karyotype, del(17) and del(11q) need to be considered in the risk stratification system for CLL.

Changes in Psychological Anxiety and Physiological Stress Hormones in Korea National Shooters.

Psychological anxiety and physiological stress hormone management is closely related to an athlete's performance, especially in shooting competitions. Thus, we aimed to investigate the changes in saliva stress hormones according to anxiety scores of Korean elite shooters immediately before a shooting competition. Seventy-two Korean national shooting athletes (Rifle = 62, Pistol = 8, Shotgun = 2) were recruited for the present study. The physiological stress hormones were assessed based on cortisol and immunoglobulin A level in saliva. The psychological stress was assessed based on Beck Anxiety Inventory (BAI) questionnaire. Cortisol concentration and cortisol secretion rate were significant higher in severe anxiety group. Secretory immunoglobulin A (SIgA) concentration and SIgA secretion rate did not significant different in among the groups. A positive correlation was found between BAI score and cortisol concentration. These findings provide preliminary evidence indicating that psychological anxiety affects physiological stress and therefore may have a negative effect on athletes' performance. Thus, research is needed to develop a strategy to reduce physiological stress in these athletes.

The Effects of Self-Talk on Shooting Athletes' Motivation.

Self-talk is helpful in motivating shooting athletes and promoting effortful behavior. This study aimed to examine how the degree and intensity of self-talk of shooting athletes during matches affects their actual internal motivation and careers. In particular, the primary objective was to determine the effects of the level and intensity of self-talk on the effort value, fun and interest, tension and anxiety, and competence of intrinsic motivation for different levels of achievement and athletic performance. One hundred seventy participants who were shooting athletes registered with the Korea Shooting Federation (national team, n = 55; high performance team, n = 62; general team, n = 53). The self-talk questionnaire was developed to measure the Test of Performance Strategies (TOPS). The intrinsic motivation scale developed and applicable to sports situations was used to measure the motivation of the shooting athletes. Significant differences were observed using MANOVA as well as the basic statistics of intrinsic motivation by self-talk. The intrinsic motivation self-talk was correlated to effort value, fun and interest, and competence. There was a significant relationship between shooting athletes' self-talk and intrinsic motivation. This study indicated that athletes using self-talk experienced more fun and interest, and they perceived higher effort value and competence. Further, the multiple regression analysis revealed that self-talk affected the intrinsic motivational factors of effort value and fun and interest.

Incidence, reasons, and risk factors for 30-day readmission after lumbar spine surgery for degenerative spinal disease.

This study investigated risk factors for 30-day readmission of discharged patients who had undergone lumbar spinal surgery. This retrospective, case-control study reviewed 3,933 patients discharged after elective spinal surgery for lumbar degenerative diseases from 2005 to 2012 at a university hospital. Of these patients, 102 were re-hospitalized within 30 days of discharge. Patient medical records were reviewed. The incidence of readmission within 30 days was 2.6%, and uncontrolled pain was the most common reason for readmission. In the univariate analysis, age, mental illness, the number of medical comorbidities, previous spinal surgery, fusion surgery, number of fusion levels, estimated blood loss, operation time, intensive care unit (ICU) admission, length of hospital stays, and total medical expenses were associated with a higher risk of readmission within 30 days. Multiple logistic regression analysis revealed that previous spinal surgery, operation time, ICU admission, length of hospital stays, and total medical expenses were independent risk factors for 30-day readmission. Independent risk factors for readmission were longer operation time, a previous spinal surgery, ICU admission, longer hospital stays, and higher medical expenses. Further studies controlling these risk factors could contribute to reducing readmission and thus improving the quality of care.