Effects of aromatherapy on nausea and vomiting in patients with cancer: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: and purpose: Aromatherapy offers a low-risk solution for effectively managing common nausea and vomiting in cancer patients. This systematic review and meta-analysis aimed to assess its impact on these symptoms to facilitate practical guidelines establishment. METHODS: PubMed, Web of Science, Cochrane Library, MEDLINE, CINAHL, and Embase were searched for articles published until April 30, 2023. Inclusion criteria were randomized controlled trials (RCTs) on the effect of aromatherapy on nausea and vomiting in patients with cancer (age ≥18 years). The effect size was calculated using standardized mean differences (SMDs) with a random effects model. Subgroup analyses, meta-analysis of variance, and meta-regression were performed using the "meta" package in R version 4.0.2. Heterogeneity was assessed using I2 statistics. Sensitivity and publication bias analyses were performed; two reviewers independently assessed risk of bias using Cochrane's risk-of-bias tool 2.0. RESULTS: Twenty-five RCTs across 10 articles revealed that aromatherapy reduced overall nausea and vomiting in patients with cancer with significant efficacy (SMD = -0.81, 95 % confidence interval [CI]: -1.11 to -0.52). Furthermore, aromatherapy reduced nausea (SMD = -0.85, 95 % CI: -1.23 to -0.46) and combined nausea and vomiting (SMD = -1.08, 95 % CI: -1.68 to -0.47), but not vomiting alone (SMD = -0.24, 95 % CI: -1.03 to 0.55). Inhalation and massage yielded positive results, especially in chemotherapy-induced cases; peppermint oil was particularly successful. CONCLUSION: Our findings underscore aromatherapy's value in managing cancer treatment-associated nausea and vomiting. Conclusive evidence on aromatherapy-led nausea reduction is lacking due to limited RCTs; research is warranted for robust conclusions.

A consortia of clinical E. coli strains with distinct in vitro adherent/invasive properties establish their own co-colonization niche and shape the intestinal microbiota in inflammation-susceptible mice.

BACKGROUND: Inflammatory bowel disease (IBD) patients experience recurrent episodes of intestinal inflammation and often follow an unpredictable disease course. Mucosal colonization with adherent-invasive Escherichia coli (AIEC) are believed to perpetuate intestinal inflammation. However, it remains unclear if the 24-year-old AIEC in vitro definition fully predicts mucosal colonization in vivo. To fill this gap, we have developed a novel molecular barcoding approach to distinguish strain variants in the gut and have integrated this approach to explore mucosal colonization of distinct patient-derived E. coli isolates in gnotobiotic mouse models of colitis. RESULTS: Germ-free inflammation-susceptible interleukin-10-deficient (Il10-/-) and inflammation-resistant WT mice were colonized with a consortium of AIEC and non-AIEC strains, then given a murine fecal transplant to provide niche competition. E. coli strains isolated from human intestinal tissue were each marked with a unique molecular barcode that permits identification and quantification by barcode-targeted sequencing. 16S rRNA sequencing was used to evaluate the microbiome response to E. coli colonization. Our data reveal that specific AIEC and non-AIEC strains reproducibly colonize the intestinal mucosa of WT and Il10-/- mice. These E. coli expand in Il10-/- mice during inflammation and induce compositional dysbiosis to the microbiome in an inflammation-dependent manner. In turn, specific microbes co-evolve in inflamed mice, potentially diversifying E. coli colonization patterns. We observed no selectivity in E. coli colonization patterns in the fecal contents, indicating minimal selective pressure in this niche from host-microbe and interbacterial interactions. Because select AIEC and non-AIEC strains colonize the mucosa, this suggests the in vitro AIEC definition may not fully predict in vivo colonization potential. Further comparison of seven E. coli genomes pinpointed unique genomic features contained only in highly colonizing strains (two AIEC and two non-AIEC). Those colonization-associated features may convey metabolic advantages (e.g., iron acquisition and carbohydrate consumption) to promote efficient mucosal colonization. CONCLUSIONS: Our findings establish the in vivo mucosal colonizer, not necessarily AIEC, as a principal dysbiosis driver through crosstalk with host and associated microbes. Furthermore, we highlight the utility of high-throughput screens to decode the in vivo colonization dynamics of patient-derived bacteria in murine models. Video Abstract.

Effects of Aromatherapy on Cancer Patients' Sleep and Fatigue: A Systematic Review and Meta-Analysis.

Objective: This study aims at investigating the effectiveness of aromatherapy in enhancing sleep quality and reducing fatigue among cancer patients based on randomized controlled trials (RCTs) with a high level of evidence. Design: A systematic review and meta-analysis. Methods: Two reviewers screened and reviewed the full texts of search results obtained from six English databases and four Korean databases, and they extracted data from the selected studies independently. Risk of bias (RoB) was assessed using the revised Cochrane RoB tool for randomized trials. The review protocol was registered with the International Prospective Register of Systematic Reviews (CRD42021277515). Results: Eleven RCTs were included in this study. Aromatherapy significantly improved sleep quality among cancer patients compared with those in the control groups (routine care, no intervention, and placebo) (standardized mean difference [SMD] = -0.92, 95% confidence interval [CI]: -1.39 to -0.46; p < 0.001, I2 = 89%). However, aromatherapy did not significantly reduce fatigue among such patients (SMD = -0.40, 95% CI: -0.81 to 0.01). The results of the meta-regression confirmed that increased intervention sessions resulted in the enhanced effectiveness of aromatherapy in improving sleep quality among cancer patients (Z = -3.86, p < 0.001). Conclusion: This study showed that aromatherapy significantly improves sleep quality among cancer patients. However, aromatherapy does not significantly reduce fatigue among cancer patients. It is possible that the statistical power of the meta-analysis was weak due to the small number of included studies. Therefore, in future studies, the effects of aromatherapy on fatigue among cancer patients should be assessed further using a larger number of included studies. Further, the effects of aromatherapy should be evaluated with a focus on specific subsets of patients, such as specific cancer diagnoses and specific modalities for cancer treatment.

Microenvironmental Factors that Shape Bacterial Metabolites in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a significant global health problem that involves chronic intestinal inflammation and can involve severe comorbidities, including intestinal fibrosis and inflammation-associated colorectal cancer (CRC). Disease-associated alterations to the intestinal microbiota often include fecal enrichment of Enterobacteriaceae, which are strongly implicated in IBD development. This dysbiosis of intestinal flora accompanies changes in microbial metabolites, shaping host:microbe interactions and disease risk. While there have been numerous studies linking specific bacterial taxa with IBD development, our understanding of microbial function in the context of IBD is limited. Several classes of microbial metabolites have been directly implicated in IBD disease progression, including bacterial siderophores and genotoxins. Yet, our microbiota still harbors thousands of uncharacterized microbial products. In-depth discovery and characterization of disease-associated microbial metabolites is necessary to target these products in IBD treatment strategies. Towards improving our understanding of microbiota metabolites in IBD, it is important to recognize how host relevant factors influence microbiota function. For example, changes in host inflammation status, metal availability, interbacterial community structure, and xenobiotics all play an important role in shaping gut microbial ecology. In this minireview, we outline how each of these factors influences gut microbial function, with a specific focus on IBD-associated Enterobacteriaceae metabolites. Importantly, we discuss how altering the intestinal microenvironment could improve the treatment of intestinal inflammation and associated disorders, like intestinal fibrosis and CRC.

Inhibition of PP2A activity by H2O2 during mitosis disrupts nuclear envelope reassembly and alters nuclear shape.

Many types of cancer cells exhibit abnormal nuclear shapes induced by various molecular changes. However, whether reactive oxygen species (ROS) induce nuclear deformation has not been fully addressed. Here, we show that hydrogen peroxide (H2O2) treatment induced concentration-dependent alterations in nuclear shape that were abolished by pretreatment with the antioxidant N-acetyl-L-cysteine or by catalase overexpression. Interestingly, treatment with H2O2 induced nuclear shape alterations significantly more frequently in mitotic cells than in asynchronous cells, suggesting that H2O2 mainly affects nuclear envelope disassembly and/or reassembly processes. Because protein phosphatase 2 A (PP2A) activity is reported to be involved in nuclear envelope reassembly during mitosis, we investigated the possible involvement of PP2A. Indeed, H2O2 reduced the activity of PP2A, an effect that was mimicked by the PP1 and PP2A inhibitor okadaic acid. Moreover, overexpression of PP2A but not PP1 or PP4 partially rescued H2O2-induced alterations in nuclear shape, indicating that the decrease in PP2A activity induced by H2O2 is specifically involved in the observed nuclear shape alterations. We further show that treatment of mitotic cells with H2O2 induced the mislocalization of BAF (barrier-to-autointegration factor), a substrate of PP2A, during telophase. This effect was associated with Lamin A/C mislocalization and was rescued by PP2A overexpression. Collectively, our findings suggest that H2O2 preferentially affects mitotic cells through PP2A inhibition, which induces the subsequent mislocalization of BAF and Lamin A/C during nuclear envelope reassembly, leading to the formation of an abnormal nuclear shape.

ATP depletion during mitotic arrest induces mitotic slippage and APC/CCdh1-dependent cyclin B1 degradation.

ATP depletion inhibits cell cycle progression, especially during the G1 phase and the G2 to M transition. However, the effect of ATP depletion on mitotic progression remains unclear. We observed that the reduction of ATP after prometaphase by simultaneous treatment with 2-deoxyglucose and NaN3 did not arrest mitotic progression. Interestingly, ATP depletion during nocodazole-induced prometaphase arrest resulted in mitotic slippage, as indicated by a reduction in mitotic cells, APC/C-dependent degradation of cyclin B1, increased cell attachment, and increased nuclear membrane reassembly. Additionally, cells successfully progressed through the cell cycle after mitotic slippage, as indicated by EdU incorporation and time-lapse imaging. Although degradation of cyclin B during normal mitotic progression is primarily regulated by APC/CCdc20, we observed an unexpected decrease in Cdc20 prior to degradation of cyclin B during mitotic slippage. This decrease in Cdc20 was followed by a change in the binding partner preference of APC/C from Cdc20 to Cdh1; consequently, APC/CCdh1, but not APC/CCdc20, facilitated cyclin B degradation following ATP depletion. Pulse-chase analysis revealed that ATP depletion significantly abrogated global translation, including the translation of Cdc20 and Cdh1. Additionally, the half-life of Cdh1 was much longer than that of Cdc20. These data suggest that ATP depletion during mitotic arrest induces mitotic slippage facilitated by APC/CCdh1-dependent cyclin B degradation, which follows a decrease in Cdc20 resulting from reduced global translation and the differences in the half-lives of the Cdc20 and Cdh1 proteins.

DNA double-strand breaks and Aurora B mislocalization induced by exposure of early mitotic cells to H2O2 appear to increase chromatin bridges and resultant cytokinesis failure.

Aneuploidy, an abnormal number of chromosomes that is a hallmark of cancer cells, can arise from tetraploid/binucleated cells through a failure of cytokinesis. Reactive oxygen species (ROS) have been implicated in various diseases, including cancer. However, the nature and role of ROS in cytokinesis progression and related mechanisms has not been clearly elucidated. Here, using time-lapse analysis of asynchronously growing cells and immunocytochemical analyses of synchronized cells, we found that hydrogen peroxide (H2O2) treatment at early mitosis (primarily prometaphase) significantly induced cytokinesis failure. Cytokinesis failure and the resultant formation of binucleated cells containing nucleoplasmic bridges (NPBs) seemed to be caused by increases in DNA double-strand breaks (DSBs) and subsequent unresolved chromatin bridges. We further found that H2O2 induced mislocalization of Aurora B during mitosis. All of these effects were attenuated by pretreatment with N-acetyl-L-cysteine (NAC) or overexpression of Catalase. Surprisingly, the PARP inhibitor PJ34 also reduced H2O2-induced Aurora B mislocalization and binucleated cell formation. Results of parallel experiments with etoposide, a topoisomerase IIα inhibitor that triggers DNA DSBs, suggested that both DNA DSBs and Aurora B mislocalization contribute to chromatin bridge formation. Aurora B mislocalization also appeared to weaken the "abscission checkpoint". Finally, we showed that KRAS-induced binucleated cell formation appeared to be also H2O2-dependent. In conclusion, we propose that a ROS, mainly H2O2 increases binucleation through unresolved chromatin bridges caused by DNA damage and mislocalization of Aurora B, the latter of which appears to augment the effect of DNA damage on chromatin bridge formation.

Survivin protects fused cancer cells from cell death.

Tetraploidy, a potential precursor of cancer-associated aneuploidy, is produced either by cell fusion or failure of cytokinesis. In this study, low p53-expressing HeLa cells were used to address the fate of cancer cells after fusion. We found that massive cell death or growth arrest occurred a few days after fusion. Interestingly, cells with larger nuclei preferentially died after fusion, suggesting that a larger deviation of DNA content is a strong inducer of apoptosis. Notably, a fraction of cells escaped cell death. Also, the stability of survivin increased, and its localization changed preferentially to the cytosol in fused cells. Knockdown of survivin decreased the survival of fused cells, more than observed in unfused cells, showing increased dependency of fused cells on survivin. Collectively, after cancer cell fusion, some fused cells avoid the apoptotic crisis partly owing to survivin, and continue to proliferate, a process that contributes to human cancer progression. [BMB Reports 2017; 50(7): 361-366].

Aldehyde dehydrogenase is used by cancer cells for energy metabolism.

We found that non-small-cell lung cancer (NSCLC) cells express high levels of multiple aldehyde dehydrogenase (ALDH) isoforms via an informatics analysis of metabolic enzymes in NSCLC and immunohistochemical staining of NSCLC clinical tumor samples. Using a multiple reaction-monitoring mass spectrometry analysis, we found that multiple ALDH isozymes were generally abundant in NSCLC cells compared with their levels in normal IMR-90 human lung cells. As a result of the catalytic reaction mediated by ALDH, NADH is produced as a by-product from the conversion of aldehyde to carboxylic acid. We hypothesized that the NADH produced by ALDH may be a reliable energy source for ATP production in NSCLC. This study revealed that NADH production by ALDH contributes significantly to ATP production in NSCLC. Furthermore, gossypol, a pan-ALDH inhibitor, markedly reduced the level of ATP. Gossypol combined with phenformin synergistically reduced the ATP levels, which efficiently induced cell death following cell cycle arrest.

Efficacy of pamidronate in pediatric osteosarcoma patients with low bone mineral density.

PURPOSE: Most surviving pediatric osteosarcoma patients experience osteoporosis, bone pain, and pathologic fracture during and after therapy. The aim of this study was to evaluate the efficacy and side effects of pamidronate therapy in these patients. METHODS: Nine osteosarcoma patients (12.8±1.6 years of age; 5 boys and 4 girls) who had a history of nontraumatic fracture or severe pain after completing chemotherapy were included. Intravenous pamidronate (1.5 mg/kg) was given every 6 weeks for 4 to 6 cycles. Bone mineral density (BMD) of the lumbar spine was measured by dual-energy x-ray absorptiometry. Clinical outcomes including acute side effects were also evaluated. RESULTS: After pamidronate treatments, all patients experienced decreased pain. Seven of 9 patients could walk without a crutch. The BMD of lumbar spine was increased by 0.108±0.062 mg/cm(2) after 8.4±1.0 months (n=8, P=0.017) and the mean z-score improved from -2.14±0.94 to -1.76±0.95 (P=0.161). Six patients (67%) had an acute-phase reaction, and 2 patients had symptomatic hypocalcemia. CONCLUSION: Pamidronate appears to be safe and effective for the treatment of osteosarcoma in children with low BMD and bone pain.

Early menarche is associated with metabolic syndrome and insulin resistance in premenopausal Korean women.

In pediatrics, identifying risk factors is important in planning the prevention of cardiovascular disease. The aim of this study was to determine whether there is an independent association between early menarche (<12 years) and metabolic syndrome (MetS) in Korean women. We analyzed data from 4463 premenopausal women from the Fourth Korea National Health and Nutrition Examination Survey-IV (2007-2009). MetS was defined by the International Diabetes Federation for Asians and insulin resistance (IR) was defined as HOMA-IR more than 3.05. The prevalence of MetS and IR was 7.9 and 15.0%. Women (55.6%) with MetS also showed IR. The prevalence of MetS was higher in both women with early menarche and late menarche (≥16 years) compared with the reference group (early, 12.8%; reference, 7.0%; late, 11.0%, both P = 0.002). However, the odds ratio for MetS was 3.54 (95% confidence interval (CI), 2.14-5.87) and for IR was 2.98 (95% CI, 1.99-4.47) after adjusting for age and other confounders such as lifestyle variables, reproductive variables and sociodemographic variables only in women with early menarche CONCLUSION: Early menarche was associated with an increased risk of MetS and IR in premenopausal Korean women. WHAT IS KNOWN: Early menarche is associated with higher risk of CVD-related death and all-cause mortality in Western studies. Early menarche is associated with higher risk of diabetes in Korean premenopausal women. WHAT IS NEW: Early menarche (<12 years) is associated with metabolic syndrome and insulin resistance in nationally representative Korean premenopausal women. However, late menarche (>16 years) is not associated with metabolic syndrome after controlling for age and other confounders.

Bone mineral density change during adjuvant chemotherapy in pediatric osteosarcoma.

PURPOSE: Osteoporosis is currently receiving particular attention as a sequela in survivors of childhood osteosarcoma. The aim of this study was to evaluate bone mineral density (BMD) changes during methotrexate-based chemotherapy in children and adolescents with osteosarcoma. METHODS: Nine patients with osteosarcoma were included in this retrospective study and compared with eight healthy controls. BMD of the lumbar spine and unaffected femur neck of patients was serially measured by dual-energy x-ray absorptiometry (DXA) before and just after chemotherapy and compared with controls. RESULTS: Four patients (44%) showed decreased lumbar spine BMD and seven patients (78%) showed decreased femur neck BMD, while all controls showed increased lumbar and femur BMD (P=0.024 and P=0.023). The femur neck BMD z-scores decreased from -0.49±1.14 to -1.63±1.50 (P=0.032). At the end of therapy, five patients (56%) showed femur neck BMD z-scores below -2.0. CONCLUSION: The bone metabolism is disturbed during therapy in children with osteosarcoma, resulting in a reduced BMD with respect to healthy controls. Since a reduced BMD predisposes to osteoporosis, specific attention and therapeutic interventions should be considered.

Factors Affecting Survival in Patients Undergoing Palliative Spine Surgery for Metastatic Lung and Hepatocellular Cancer: Dose the Type of Surgery Influence the Surgical Results for Metastatic Spine Disease?

BACKGROUND: Surgical treatment for metastatic spine disease has been becoming more prominent with the help of technological advances and a few favorable reports on the surgery. In cases of this peculiar condition, it is necessary to establish the role of surgery and analyze the factors affecting survival. METHODS: From January 2011 to April 2015, 119 patients were surgically treated for metastatic spine lesions. To reduce the bias along the heterogeneous cancers, the primary cancer was confined to either the lung (n = 25) or the liver (n = 18). Forty-three patients (male, 32; female, 11; mean age, 57.5 years) who had undergone palliative surgery were enrolled in this study. Posterior decompression and fusion was performed in 30 patients (P group), and anteroposterior (AP) reconstruction was performed in 13 patients (AP group) for palliative surgery. Pre- and postoperative (3 months) pain (visual analogue scale, VAS), performance status (Karnofsky performance score), neurologic status (American Spinal Injury Association [ASIA] grade), and spinal instability neoplastic score (SINS) were compared. The survival period and related hazard factors were also assessed by Kaplan-Meier and Cox regression analysis. RESULTS: Most patients experienced improvements in pain and performance status (12.3% ± 17.2%) at 3 months postoperatively. In terms of neurologic recovery, 9 patients (20.9%) graded ASIA D experienced neurological improvement to ASIA E while the remainder was status quo. In an analysis according to operation type, there was no significant difference in patient demographics. At 12 months postoperatively, cumulative survival rates were 31.5% and 38.7% for the P group and the AP group, respectively (p > 0.05). Survival was not affected by the pre- and postoperative pain scale, Tokuhashi score, neurologic status, SINS, or operation type. Preoperative Karnofsky performance score (hazard ratio, 0.93; 95% confidence interval [CI], 0.89 to 0.96) and improvement of performance status after surgery (hazard ratio, 0.95; 95% CI, 0.92 to 0.97) significantly affected survival after operation. CONCLUSIONS: There was no significant difference in surgical outcomes and survival rates between posterior and AP surgery for metastatic lesions resulting from lung and hepatocellular cancer. Preoperative Karnofsky score and improvement of performance status had a significant impact on the survival rate following surgical treatment for these metastatic spine lesions.

New Korean reference for birth weight by gestational age and sex: data from the Korean Statistical Information Service (2008-2012).

PURPOSE: To construct new Korean reference curves for birth weight by sex and gestational age using contemporary Korean birth weight data and to compare them with the Lubchenco and the 2010 United States (US) intrauterine growth curves. METHODS: Data of 2,336,727 newborns by the Korean Statistical Information Service (2008-2012) were used. Smoothed percentile curves were created by the Lambda Mu Sigma method using subsample of singleton. The new Korean reference curves were compared with the Lubchenco and the 2010 US intrauterine growth curves. RESULTS: Reference of the 3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentiles birth weight by gestational age were made using 2,249,804 (male, 1,159,070) singleton newborns with gestational age 23-43 weeks. Separate birth weight curves were constructed for male and female. The Korean reference curves are similar to the 2010 US intrauterine growth curves. However, the cutoff values for small for gestational age (<10th percentile) of the new Korean curves differed from those of the Lubchenco curves for each gestational age. The Lubchenco curves underestimated the percentage of infants who were born small for gestational age. CONCLUSION: The new Korean reference curves for birth weight show a different pattern from the Lubchenco curves, which were made from white neonates more than 60 years ago. Further research on short-term and long-term health outcomes of small for gestational age babies based on the new Korean reference data is needed.

Age at menarche in the Korean female: secular trends and relationship to adulthood body mass index.

PURPOSE: The objective of this study is to estimate the trend in age at menarche in the Korean female and evaluate the relationship between age at menarche and adult body mass index (BMI), which is a indicator of later-life health. METHODS: We conducted a cross-sectional analysis of a nationally representative sample (self-reported age at menarche and measured height and weight) of 11,065 females aged 15 and older. Data were obtained from the Fourth Korea National Health and Nutrition Examination Survey (KNHANES IV, 2007-2009). RESULTS: We found a statistically significant decline in age at menarche in successive birth groups, indicating a 0.726 year decrease per decade. The age at menarche in 1990-1994 year birth group was 12.60 years, which showed a significant decreased from 3.11 years in the 1980-1984 birth group. We also found a significant negative association between age at menarche and current BMI. A one-year decrease in age at menarche was associated with mean BMI increase of 0.109 kg/m(2) (95% confidence interval [CI], 0.069 to 0.150) after adjustment for age. In multivariate logistic regression, the odds ratios of obesity in females with early menarche (<12 years) was 1.845 fold (95% CI, 1.441 to 2.361). CONCLUSION: We found that age at menarche is still falling in the Korean female. We also found that early menarche is a risk factor for obesity in adults.

Drosophila castor is regulated negatively by the Ubx and abdA genes, but positively by the AbdB gene.

The ventral nerve cord (VNC) of Drosophila exhibits significant segmental-specific characteristics during embryonic development. Homeotic genes are expressed over long periods of time and confer identity to the different segments. castor (cas) is one of the genes which are expressed in neuroblasts along the VNC. However, at late embryonic stages, cas transcripts are found only in head and thoracic segments and terminal abdominal segments, while Cas protein lasts longer in all segments. In this study, we investigated the regulation of temporal and spatial expression of cas by the bithorax complex genes. In the loss-of-function mutants of Ultrabithorax (Ubx) and abdominal-A (abdA), cas transcripts were ectopically expressed in abdominal segments at late embryonic stage. However, unlike in Ubx and abdA mutants, in Abdominal-B (AbdB) loss-of-function mutant embryos, cas disappeared in the terminal region. Ectopic Ubx and abdA suppressed cas expression, but ectopic AbdB activated cas expression in most abdominal segments. Moreover, cas was co-expressed in the cells in which AbdB was normally expressed, and overexpressed in the ectopically expressed AbdB embryos. These results suggest that the expression of cas is segment-specifically regulated negatively by Ubx and abdA genes, but positively by the AbdB gene.