Cadmium alters whole animal ionome and promotes the re-distribution of iron in intestinal cells of Caenorhabditis elegans.

The chronic exposure of humans to the toxic metal cadmium (Cd), either occupational or from food and air, causes various diseases, including neurodegenerative conditions, dysfunction of vital organs, and cancer. While the toxicology of Cd and its effect on the homeostasis of biologically relevant elements is increasingly recognized, the spatial distribution of Cd and other elements in Cd toxicity-caused diseases is still poorly understood. Here, we use Caenorhabditis elegans as a non-mammalian multicellular model system to determine the distribution of Cd at the tissue and cellular resolution and its effect on the internal levels and the distribution of biologically relevant elements. Using inductively coupled plasma-mass spectrophotometry (ICP-MS), we show that exposure of worms to Cd not only led to its internal accumulation but also significantly altered the C. elegans ionome. Specifically, Cd treatment was associated with increased levels of toxic elements such as arsenic (As) and rubidium (Rb) and a decreased accumulation of essential elements such as zinc (Zn), copper (Cu), manganese (Mn), calcium (Ca), cobalt (Co) and, depending on the Cd-concentration used in the assay, iron (Fe). We regarded these changes as an ionomic signature of Cd toxicity in C. elegans. We also show that supplementing nematode growth medium with Zn but not Cu, rescues Cd toxicity and that mutant worms lacking Zn transporters CDF-1 or SUR-7, or both are more sensitive to Cd toxicity. Finally, using synchrotron X-Ray fluorescence Microscopy (XRF), we showed that Cd significantly alters the spatial distribution of mineral elements. The effect of Cd on the distribution of Fe was particularly striking: while Fe was evenly distributed in intestinal cells of worms grown without Cd, in the presence of Cd, Fe, and Cd co-localized in punctum-like structures in the intestinal cells. Together, this study advances our understanding of the effect of Cd on the accumulation and distribution of biologically relevant elements. Considering that C. elegans possesses the principal tissues and cell types as humans, our data may have important implications for future therapeutic developments aiming to alleviate Cd-related pathologies in humans.

A 6-Week Program to Strengthen Resiliency Among Women With Metastatic Cancer: A Randomized Clinical Trial.

PURPOSE: The objective of this study was to evaluate the effect of an intervention (Growing Resilience And CouragE; GRACE) on spiritual well-being, quality of life, and general well-being in women with metastatic cancers reporting existential or spiritual distress. PATIENTS AND METHODS: Prospective, randomized, wait-list control clinical trial. Women with metastatic cancer experiencing existential or spiritual concerns were randomized to GRACE or waitlist control. Survey data were collected at baseline, end of program, and 1-month follow-up. Participants included English-speaking women, 18 or older, with metastatic cancer, existential or spiritual concerns, and reasonable medical stability. Eighty-one women were assessed for eligibility; 10 were excluded (not meeting exclusion criteria, refusal to participate, and death). The primary outcome was spiritual well-being measured pre- and post-program. Secondary measures assessed quality of life, anxiety, depression, hopelessness, and loneliness. RESULTS: Seventy-one women (aged 47-72) were enrolled (GRACE n = 37, waitlist control n = 34). GRACE participants demonstrated significant improvements in spiritual well-being compared to control at end of program (parameter estimate (PE), 16.67, 95% CI, 13.17, 20.16) and 1-month follow-up (PE, 10.31, 95% CI, 6.73, 13.89). Additionally, significant improvements were demonstrated in quality of life at the end of program (PE, 8.51, 95% CI, 4.26, 12.76) and 1-month follow-up (PE, 6.17, 95% CI, 1.75, 10.58). GRACE participants also demonstrated improved depression and hopelessness at follow-up, as well as improved anxiety. CONCLUSIONS: Findings suggest the value of evidence-based psychoeducational and experiential interventions for improving the well-being and quality of life of women with advanced cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02707510.

Causal impact analysis of enhanced phosphorus effluent standard on river water quality.

The effect of environmental policies on water quality is an important factor in evaluating a project's impact and economic feasibility. The aim of this study was to evaluate the causal relationship between strengthening the total phosphorus (TP) concentration standard in wastewater treatment plant (WWTP) effluents and river water quality in the Geum River watershed (Rep. of Korea). Data, including precipitation, streamflow, and water quality, were collected for 2005-2020 and temporally divided into "before" and "after" the event of strengthening standards (in 2012). Further, the data were spatially divided into influence sites (impact) affected by the event and control sites (control) unaffected by the event. A median difference test for a before/after and control/impact (BACI) analysis and a causal impact analysis (CIA) based on a Bayesian structural time-series model were performed to evaluate the changes in water quality after the event. The BACI test showed that the TP concentration was reduced significantly (p-value<0.05) at all impact sites after the event, whereas the difference was not significant at the control sites. In contrast, other water quality variables, except TP, showed different statistical significance depending on the site. The CIA was performed by controlling the rainfall, flow rate, suspended solids, water temperature, biochemical oxygen demand, and chemical oxygen demand as covariates, which were selected based on a directed acyclic graph and bi-variable correlation analysis. The CIA results showed that the TP concentration was reduced significantly (p-value<0.05) at all impact sites, except for the control sites after the event, which is consistent with the BACI results. The causal impact of environmental management policies was previously difficult to evaluate by objectively targeting the natural systems because of the confounding bias. Our study demonstrated that strengthening the TP concentration standard from WWTPs majorly contributed to reducing TP in the receiving river, even when confounding factors, such as fluctuations in non-point source pollution loads caused by rainfall and runoff, were excluded. The statistical approaches used in this study can be valuable and practical methods for such evaluations if sufficient prior and posterior data and appropriate covariates are obtained.

Metabolic Bone Diseases and New Drug Developments.

Metabolic bone diseases are serious health issues worldwide, since several million individuals over the age of 50 are at risk of bone damage and should be worried about their bone health. One in every two women and one in every four men will break a bone during their lifetime due to a metabolic bone disease. Early detection, raising bone health awareness, and maintaining a balanced healthy diet may reduce the risk of skeletal fractures caused by metabolic bone diseases. This review compiles information on the most common metabolic bone diseases (osteoporosis, primary hyperparathyroidism, osteomalacia, and fluorosis disease) seen in the global population, including their symptoms, mechanisms, and causes, as well as discussing their prevention and the development of new drugs for treatment. A large amount of research literature suggests that balanced nutrition and balanced periodic supplementation of calcium, phosphate, and vitamin D can improve re-absorption and the regrowth of bones, and inhibit the formation of skeletal fractures, except in the case of hereditary bone diseases. Meanwhile, new and improved drug formulations, such as raloxifene, teriparatide, sclerostin, denosumab, and abaloparatide, have been successfully developed and administered as treatments for metabolic bone diseases, while others (romososumab and odanacatib) are in various stages of clinical trials.

Preparation and Optimization of Peppermint (Mentha pipertia) Essential Oil Nanoemulsion with Effective Herbal Larvicidal, Pupicidal, and Ovicidal Activity against Anopheles stephensi.

OBJECTIVES: The Plasmodium parasite is transmitted directly to humans through the Anopheles mosquito bite and causes vector-borne malaria, leading to the transmission of the disease in Southeast Asia, including India. The problem of persistent toxicity, along with the growing incidence of insect resistance, has led to the use of green pesticides to control the spread of the disease in a cost-effective and environment-friendly manner. Based on this objective, this work investigated the larvicidal, pupicidal, and ovicidal activity of Mentha pipertia using a natural nanoemulsion technique. METHODS: GC-MS characterized essential oils of Mentha pipertia leaves were formulated as a nanoemulsion for herbal larvicidal, pupicidal, and ovicidal activities. Size of the nanoemulsion was analyzed by photon correlation spectroscopy. The herbal activities against Anopheles Stephensi of nanoemulsion were evaluated in terms of the lethal concentration for 50% (LC50) and 90% (LC90) to prove low cost, pollution free active effective formulation. RESULTS: Chiral, keto, and alcohol groups are obtained from Mentha pipertia leaves' essential oil, and the nanoemulsions have demonstrated good results in the larvicidal probit analysis, with values of LC50=09.67 ppm and LC90=20.60 ppm. Activity results of the most stable nano formulation with 9.89 nm size showed a significant increase when compared to the bulk. CONCLUSION: The nanoemulsion of Mentha pipertia leaves can be a promising eco-friendly widely available, low-cost herbicide against the Anopheles mosquito.

High-dose-rate fractionated brachytherapy monotherapy for localized prostate cancer: a systematic review and meta-analysis.

PURPOSE: High-dose-rate (HDR) brachytherapy as primary therapy (monotherapy) is a standard National Comprehensive Cancer Network (NCCN) endorsed treatment option for patients with localized prostate cancer. Thus far, most data are limited to single-institution experiences. Accordingly, we sought to systematically review rates of biochemical recurrence-free survival (bRFS) and toxicity associated with fractionated HDR monotherapy. MATERIAL AND METHODS: A systematic review was performed using PubMed and Embase databases for relevant articles published between January 1999 and December 2019, according to preferred reporting items for systematic review and meta-analyses (PRISMA) guidelines. Included studies were limited to fractionated HDR monotherapy publications in full manuscript form with at least 5-year median follow-up, at least 80 patients included, and adequate reporting of bRFS and toxicity data. Meta-analyses were performed with random-effect modeling. Extent of heterogeneity between studies was determined using I 2 and Cochran's Q tests. RESULTS: Seven unique studies were identified, including 2,123 patients. NCCN low-, intermediate-, and high-risk patients comprised 40%, 40%, and 20% of patients, respectively. Median follow-up at the study group level was 74 months (range, 60-131 months). The 5-year bRFS rate was 95% (95% confidence interval [CI]: 93-96%), and after adjusting to control for publication bias, it was 96% (95% CI: 94-99%). Estimated adjusted late grade ≥ 3 genitourinary and gastrointestinal toxicity rates were 2% (95% CI: 1-4%) and 0.3% (95% CI: 0-1.1%), respectively. CONCLUSIONS: Fractionated HDR monotherapy is associated with high rates of disease control and low rates of toxicity. Future studies are needed to better define the value of this treatment modality relative to other options.

Prognostic Implications of Chemotherapy-Induced Neutropenia in Stage III Colorectal Cancer.

BACKGROUND: Previous studies have reported chemotherapy-induced neutropenia (CIN) as a prognostic factor in stage IV colorectal cancer (CRC). However, only few reports analyzed the prognostic value of CIN in patients with stage III CRC who received adjuvant chemotherapy with oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX). We aimed to investigate the prognostic implications of CIN in patients with stage III CRC who received adjuvant chemotherapy with FOLFOX. MATERIALS AND METHODS: We retrospectively analyzed patients with stage III CRC who received adjuvant chemotherapy with FOLFOX at a tertiary hospital between January 2007 and December 2017. Severe CIN was defined as an absolute neutrophil count of less than 1000/mm3. Three-y disease-free survival (DFS) and overall survival (OS) were analyzed as primary endpoints. RESULTS: Among the 199 patients included in this study, 110 patients (55.3%) experienced severe CIN. There were no significant differences in survival outcomes between the control and CIN groups (control group versus CIN group: 3-y OS, 82.0 % versus 72.7 %; log rank, P = 0.250 and 3-y DFS, 71.9 % versus 62.7; log rank, P = 0.294). Univariate and multivariate analyses revealed that CIN did not affect DFS and OS in patients with stage III CRC who received adjuvant FOLFOX chemotherapy. CONCLUSIONS: Severe CIN occurring during adjuvant FOLFOX chemotherapy did not play a significant role in the prognosis of patients with stage III CRC.

The Leveraging Exercise to Age in Place (LEAP) Study: Engaging Older Adults in Community-Based Exercise Classes to Impact Loneliness and Social Isolation.

OBJECTIVE: Social isolation and loneliness are associated with morbidity and mortality in older adults. Limited evidence exists regarding which interventions improve connectedness in this population. DESIGN/SETTING/PARTICIPANTS: In this pre-post study we assessed community-based group health class participants' (age ≥50) loneliness and social isolation. Participants (n = 382) were referred by a Cedars-Sinai Medical Network (Los Angeles, California) healthcare provider or self-referred from the community (July 2017-March 2020). INTERVENTION: Participants met with a program coordinator and selected Arthritis Exercise, Tai Chi for Arthritis, EnhanceFitness, or the Healthier Living Workshop. MEASUREMENTS: We measured social isolation using the Duke Social Support Index (DSSI) and loneliness using the UCLA 3-item Loneliness Scale at baseline, class completion, and 6 months. RESULTS: Mean age was 76.8 years (standard deviation, SD = 9.1); 315 (83.1%) were female; 173 (45.9%) were Non-Hispanic white; 143 (37.9%) were Non-Hispanic Black; 173 (46.1%) lived alone; mean baseline DSSI score was 26.9 (SD = 4.0) and mean baseline UCLA score was 4.8 (SD = 1.8). On multivariable analysis adjusted for gender, race/ethnicity, income, self-rated health, and household size, DSSI improved by 2.4% at 6-week compared to baseline (estimated ratio, ER: 1.024; 95% confidence interval [CI]: 1.010-1.038; p-value = 0.001), and 3.3% at 6-month (ER: 1.033; 95% CI: 1.016-1.050; p-value <0.001). UCLA score after adjusting for age, gender, race/ethnicity, live alone, number of chronic conditions, income, and self-rated health, did not change at 6-week (ER: 0.994; 95% CI: 0.962-1.027; p-value = 0.713), but decreased by 6.9% at 6-months (ER: 0.931; 95% CI: 0.895-0.968; p-value <0.001). CONCLUSION: Community-based group health class participants reported decreased loneliness and social isolation at 6-month follow-up.

Neural regulation of energy and bone homeostasis by the synaptic adhesion molecule Calsyntenin-3.

Neuronal regulation of energy and bone metabolism is important for body homeostasis. Many studies have emphasized the importance of synaptic adhesion molecules in the formation of synapses, but their roles in physiology still await further characterization. Here, we found that the synaptic adhesion molecule Calsyntenin-3 (CLSTN3) regulates energy and bone homeostasis. Clstn3 global knockout mice show reduced body mass with improved leptin sensitivity and increased energy expenditure compared to their wild-type littermates. In addition, Clstn3 knockout mice show reduced marrow volume and cortical bone mass without alteration of trabecular bone microarchitecture. This reduced bone mass is not bone cell-autonomous because neither osteoblast- nor osteoclast-specific Clstn3 knockout mice show bone defects; similarly, in vitro cultures of both Clstn3 knockout osteoblasts and osteoclasts do not show any defects. These reduced body and bone mass phenotypes can be attributed instead to neuronal CLSTN3 because they are recapitulated by pan-neuronal but not sympathetic neuron-specific deletion of Clstn3. This study reveals novel physiological functions of neuronal Clstn3 as a key regulator of energy and bone homeostasis.

Extended Intake of Mulberry Leaf Extract Delayed Metformin Elimination via Inhibiting the Organic Cation Transporter 2.

Diabetes mellitus (DM) has become a major health problem in most countries of the world. DM causes many complications, including hyperglycemia, diabetic ketoacidosis, and death. In Asia, mulberry has been used widely in the treatment of DM. Combination of drugs with herbal medicine may reduce the unwanted side effects caused by drugs. In this study, the influence of extended mulberry leaves extract (MLE) intake on metformin (Met) was evaluated in terms of pharmacokinetics and pharmacodynamics in DM-induced rats. Three week-treatment of MLE alone produced the anti-hyperglycemic effect (around 24%) if compared to the control. Interestingly, Met administration after MLE treatment for 3 weeks enhanced about 49% of the anti-hyperglycemic effect of Met. In addition, the extended intake of MLE potentiated the anti-hyperglycemic effect of Met on various concentrations. This potentiated anti-hyperglycemic effect of Met appears to be due to the pharmacokinetic change of Met. In this study, 3 week-treatment of MLE reduced the elimination of Met in DM-induced rats. In addition, MLE reduced the human organic cation transporter 2 (hOCT2) activity in a concentration-dependent manner. Thus, these findings suggest that MLE lowered the elimination of Met via inhibiting the hOCT2.

Thread-embedding acupuncture for lumbar herniated intervertebral disc: Protocol for a systematic review and meta-analysis.

BACKGROUND: Lumbar herniated intervertebral disc (LHIVD) is a frequent disease among patients attending Korean medicine hospitals, and it is associated with considerable medical expenses for the patients. Although several recent randomized clinical trials (RCTs) have reported that thread-embedding acupuncture (TEA) has a more favorable therapeutic effect on LHIVD than other types of acupuncture or other treatments, the evidence remains limited because these trials used poor assessment methods and had a high risk of bias. This study aims to evaluate the evidence for the effectiveness and safety of TEA for LHIVD. In this article, we describe our methods and plan for a systematic review. METHODS: We will conduct an electronic search of the following databases from their inception to May 2018: MEDLINE; EMBASE; COCHRANE; China National Knowledge Infrastructure (CNKI) (a Chinese database); CiNii and J-STAGE (Japanese databases); and KoreaMed, Korean Medical Database (KMbase), Korean Studies Information Service System (KISS), National Digital Science Library (NDSL), Korea Institute of Science and Technology Information (KISTI), Oriental Medicine Advanced Searching Integrated System (OASIS). RCTs investigating any type of TEA will be included. The risk of bias in each study will be evaluated using the Cochrane risk of bias tool. Risk ratios or mean differences with 95% confidence intervals will be used to show the effects of TEA if it will be possible to conduct a meta-analysis. Sensitivity analyses will also be conducted in this study. ETHICS AND DISSEMINATION: Ethical approval is not necessary as this paper does not involve patient data. The review will be published in a peer-reviewed journal or presented in a conference. TRIAL REGISTRATION NUMBER: PROSPERO CRD42019133060.

Traditional Korean Medicine Treatment for Patients with Wilting Disorder: A Literature Review of In Vivo Studies.

Wilting disorder is an abnormal condition characterized by weakness and paralysis of the upper and lower extremities. Pathogenesis and treatment target of the disorder are unclear; hence, allopathic treatment is generally used to relieve the symptoms. To investigate the treatment mechanism and effect of Traditional Korean Medicine (TKM) in patients with wilting disorder, we reviewed in vivo studies that focused on the effect of TKM on the main symptoms of wilting disorder and treatment of the diseases that can cause these symptoms. We electronically searched the PubMed, Cochrane, and CNKI (China National Knowledge Infrastructure) databases using the following search terms: (weakness OR motor function disorder) (myasthenia gravis OR Guillain-Barre syndrome OR amyotrophic lateral sclerosis OR paralysis OR polymyositis OR muscular dystrophy) AND (herbal medicine OR acupuncture OR bee-venom OR pharmacoacupuncture OR electro-acupuncture OR moxibustion). We selected 11 studies that demonstrated the effect of TKM treatment on the main symptoms of wilting disorder. In these studies, inducted models of amyotrophic lateral sclerosis, myasthenia gravis, Duchenne muscular atrophy, polymyositis, and Guillain-Barre syndrome were used. With regard to treatment, herbal medicine was used in five studies, and acupuncture and bee-venom pharmacoacupuncture were used in three studies each. Future research is needed to determine the effectiveness of TKM treatment in patients with diseases that can cause the main symptoms of wilting disorder.

Clinical research on the efficacy and safety of Bosinji for low back pain with radiculopathy caused by herniated intervertebral disc of the lumbar spine: A protocol for a multicenter, randomized, controlled equivalence trial.

BACKGROUND: A lumbar herniated intervertebral disc (LHIVD) is a common problem that usually causes low back pain and radiating pain. The effectiveness of Bosinji, one of the herbal medicines used for low back pain and radiating pain in patient with LHIVD, has been reported in several studies; however, little clinical evidence is available owing to the methodological limitations in previous studies. Hence, the present study aims to establish the clinical evidence regarding the efficacy and safety of Bosinji in improving pain, function, and quality of life in LHIVD patients. METHOD/DESIGN: This is a multicenter, open-label, randomized, controlled, and equivalence trial with 2 parallel arms. A total of 74 patients who have low back pain and radiating pain due to LHIVD will be recruited and randomly allocated to the experimental group and control group. The patients in the experimental group and control group will take 2.5 g of Bosinji granule (1.523 g of Bosinji extract) or Loxonin tablet (60 mg of loxoprofen) 3 times a day for 6 weeks. Additionally, both groups will receive the same acupuncture treatment once a week for 6 weeks as a concurrent treatment. Changes in the 100-mm visual analogue scale (VAS) for low back pain after 6 weeks from baseline will be assessed as the primary outcome. Furthermore, the 100-mm VAS for radiating pain, Oswestry disability index (ODI), Roland-Morris disability questionnaire (RMDQ), EuroQol 5 Dimensions 5 Levels (EQ-5D-5L), global perceived effect (GPE), and deficiency syndrome of kidney index (DSKI) will be used to evaluate secondary outcomes. Outcomes will be assessed at baseline and at 3, 6, and 10 weeks after screening. For the safety evaluation, laboratory examinations including complete blood count, liver function test, renal function test, blood coagulation test, inflammation test, and urine analysis will be conducted before and after taking the medications. DISCUSSION: The results of this trial will be used to establish clinical evidence regarding the use of Bosinji with acupuncture treatment in the treatment of patients with LHIVD. TRIAL REGISTRATION NUMBER: NCT03386149 (clinicaltrials.gov) and KCT0002848 (Clinical Research Information Service of the Republic of Korea).

Inhibition of inducible nitric oxide synthase and osteoclastic differentiation by Atractylodis Rhizoma Alba extract.

BACKGROUND: Atractylodis Rhizoma Alba (ARA) has been used in Korean folk medicine for constipation, dizziness, and anticancer agent. In the present study, we performed to test whether the methanolic extract of ARA has antioxidant and antiosteoclastogenesis activity in RAW 264.7 macrophage cells. MATERIALS AND METHODS: Antioxidant capacities were tested by measuring free radical scavenging activity, nitric oxide (NO) levels, reducing power, and inducible nitric oxide synthase (iNOS) expression in response to lipopolysaccharides (LPS). Antiosteoclastogenesis activity was evaluated by performing tartrate-resistant acid phosphatase assay in RAW 264.7 macrophage cells. RESULTS: The extract exerted significant 1,1-diphenyl-2-picrylhydrazyl and NO radical scavenging activity, and it exerted dramatic reducing power. Induction of iNOS and NO by LPS in RAW 264.7 cells was significantly inhibited by the extract, suggesting that the ARA extract inhibits NO production by suppressing iNOS expression. Strikingly, the ARA extracts substantially inhibited the receptor activator of NF-κB ligand-induced osteclastic differentiation of LPS-activated RAW 264.7 cells. The ARA extract contains a significant amount of antioxidant components, including phenolics, flavonoids and anthocyanins. CONCLUSION: These results suggest that the methanolic extract of ARA exerts significant antioxidant activities potentially via inhibiting free radicals and iNOS induction, thereby leading to the inhibition of osteoclastogenesis.

Development of late blight resistant potatoes by cisgene stacking.

BACKGROUND: Phytophthora infestans, causing late blight in potato, remains one of the most devastating pathogens in potato production and late blight resistance is a top priority in potato breeding. The introduction of multiple resistance (R) genes with different spectra from crossable species into potato varieties is required. Cisgenesis is a promising approach that introduces native genes from the crops own gene pool using GM technology, thereby retaining favourable characteristics of established varieties. RESULTS: We pursued a cisgenesis approach to introduce two broad spectrum potato late blight R genes, Rpi-sto1 and Rpi-vnt1.1 from the crossable species Solanum stoloniferum and Solanum venturii, respectively, into three different potato varieties. First, single R gene-containing transgenic plants were produced for all varieties to be used as references for the resistance levels and spectra to be expected in the respective genetic backgrounds. Next, a construct containing both cisgenic late blight R genes (Rpi-vnt1.1 and Rpi-sto1), but lacking the bacterial kanamycin resistance selection marker (NPTII) was transformed to the three selected potato varieties using Agrobacterium-mediated transformation. Gene transfer events were selected by PCR among regenerated shoots. Through further analyses involving morphological evaluations in the greenhouse, responsiveness to Avr genes and late blight resistance in detached leaf assays, the selection was narrowed down to eight independent events. These cisgenic events were selected because they showed broad spectrum late blight resistance due to the activity of both introduced R genes. The marker-free transformation was compared to kanamycin resistance assisted transformation in terms of T-DNA and vector backbone integration frequency. Also, differences in regeneration time and genotype dependency were evaluated. CONCLUSIONS: We developed a marker-free transformation pipeline to select potato plants functionally expressing a stack of late blight R genes. Marker-free transformation is less genotype dependent and less prone to vector backbone integration as compared to marker-assisted transformation. Thereby, this study provides an important tool for the successful deployment of R genes in agriculture and contributes to the production of potentially durable late blight resistant potatoes.

Clinical efficacy of targeted biologic agents as second-line therapy of advanced thyroid cancer.

UNLABELLED: Targeted biologic agents showed clinically meaningful efficacy as front-line therapy for advanced radioiodine-refractory and medullary thyroid cancer. The clinical benefit of these agents beyond the front line has yet to be established. METHODS: We assessed the clinical benefit of targeted agents in patients with advanced differentiated and medullary thyroid cancer treated at a single academic cancer center. We determined efficacy and compared front-line and second-line benefit using biochemical and anatomic response, time to treatment failure, and progression-free survival (PFS). Statistical differences were assessed by t test and chi-square test. Survival curves were generated by the Kaplan-Meier method. Differences in survival were assessed using the log-rank test, and a p value <.05 was considered significant. RESULTS: We identified 39 patients with advanced differentiated and medullary thyroid cancer treated with targeted biologic agents. Median age was 56.3 years. Overall, 25 men and 14 women participated. Histology showed 23% medullary and 77% differentiated cancer. Nineteen patients progressed on front-line therapy and subsequently received second-line therapy. Targeted agents conferred clinically meaningful benefit in the second-line setting in terms of biochemical response (13.3%), clinical benefit (83.3%), median time to treatment failure (4.0 months; 95% confidence interval: 2.6-8.2), and median PFS (4.6 months; 95% confidence interval: 3.2-8.2). Second-line benefit (median PFS) was more modest in comparison to the front-line setting in both genders (women: 3 months vs. 12.2 months; men: 6 months vs. 19.7 months), in differentiated cancers (4.1 months vs. 15.7 months), and with vascular targeting agents (4.4 months vs. 20.1 months). CONCLUSION: Patients with advanced thyroid cancer derived meaningful clinical benefit from additional therapy with a biologic agent following disease progression on front-line targeted therapy.

Evaluation of the antioxidant activities and nutritional properties of ten edible plant extracts and their application to fresh ground beef.

In this study, we assessed the antioxidant efficacy and nutritional value of 10 leafy edible plants and evaluated their potential as natural antioxidants for meat preservation. We measured total phenolic content, 2,2-diphenyl-1-picryl-hydrazil (DPPH) radical scavenging activity, and vitamin C, chlorophyll, and carotenoid contents of 70% ethanol and water extracts of the edible plants. Based on these results, we investigated the effects of butterbur and broccoli extracts on lipid oxidation in ground beef patties. Plant extracts and butylated hydroxytoluene (BHT) were individually added to patties at both 0.1% and 0.5% (w/w) concentrations. Thiobarbituric acid reactive substance (TBARS) values and color parameters were tested periodically during 12 days of refrigerated storage. TBARS levels were significantly lower (p≤0.05) in the samples containing plant extracts or BHT than the non-treated control. In addition, the beef patties formulated with the selected plant extracts showed significantly (p≤0.05) better color stability than those without antioxidants. These results indicate that edible plant extracts are promising sources of natural antioxidants and can potentially be used as functional preservatives in meat products.

A single-center, randomized double-blind placebo-controlled study evaluating the effects of poly-gamma-glutamate on human NK cell activity after an 8-week oral administration in healthy volunteers.

A randomized double-blind placebo-controlled immunity study involving 99 healthy volunteers was performed to investigate the effect of poly- γ -glutamate ( γ -PGA) on human natural killer (NK) cell activity in peripheral blood. The volunteers were randomly assigned to one of three groups and orally treated with solutions (25 mL) containing 0 mg (placebo), 250 mg (low dosage), or 500 mg (high dosage) of γ -PGA. Each volunteer took one dose every 12 hours for 8 weeks. Blood samples were drawn before the initial treatment and at the 4th and the 8th weeks of treatment. NK cell activity was assessed by measuring its degranulation, cytokine production, and cytotoxicity against the K562 cell line. Our results revealed that the cytotoxic activities of NK cells from the high-dosage γ -PGA group were significantly higher (P < 0.05 for all comparisons) compared to the low dosage and placebo groups at weeks 4 and 8 after the initial treatment. This increase in the NK cell activity among peripheral blood mononuclear cells (PBMCs) of healthy individuals was also confirmed in vitro (as assessed by the degranulation and cytokine production). These results suggest that the oral administration of γ -PGA induces a cell-mediated immunity by increasing the NK cell activity in humans.

Subacute toxicological evaluation of Asiasari radix methanol extract.

Asiasari radix, a traditional herbal medicine commonly used to treat various diseases, currently has a lack of information about adverse effects. Safety information of A. radix and its extract is limited to its historical use. The safety of A. radix methanol extract was tested in an oral subacute 28-day toxicity study in both male and female Sprague-Dawley (SD) rats at doses of 50, 250, and 500 mg/kg/day. No mortality and significant signs of toxicity were observed in either the control or treated groups of both sexes. There were no significant differences in the body and organ weights or in food and water consumption. Hematological and biochemical parameters showed no changes in either the control or treated groups of both sexes. Pathologically, neither gross abnormalities nor histopathological changes were observed. Therefore, methanolic extract of A. radix appears to be safe and nontoxic in these studies, and a no observed adverse effect level in rats is established at 500 mg/kg/day, the highest dose tested.