Assessment of safety: In vitro reverse mutation and in vivo acute oral toxicity tests of three biomass products from amino acid-producing Corynebacterium glutamicum.

Microbial fermentation has emerged as a pivotal process for sustainable production of essential goods and chemicals. Corynebacterium glutamicum is a proficient platform organism that contributes significantly to amino acid production through microbial fermentation. Despite its recognized safety, challenges persist in efficiently biosynthesizing natural products compared with other organisms. This study evaluated the safety of biomass products from bioengineered C. glutamicum through two different toxicological studies: a bacterial reverse mutation test (AMES test) and an acute oral toxicity test in rats. Three types of dried fermentation biomass products, each engineered for the enhanced production of specific amino acids (L-lysine, L-threonine, and L-tryptophan), were examined. The tests were conducted in compliance with Organization for Economic Co-operation and Development guidelines and revealed no mutagenicity or acute toxicity at the tested doses. These findings suggest the safety of biomass products from bioengineered C. glutamicum as potential feed materials, although further toxicity studies are recommended for comprehensive evaluation. This study underscores the importance of stringent safety assessments for advancing biotechnological applications and provides valuable insights into the potential utilization of microbial fermentation products in various industries. Moreover, this study highlights the significance of regulatory compliance and adherence to international standards to ensure the safety and efficacy of novel biotechnological products.

Extracts of Phlomoides umbrosa Turczaninow alleviate allergic airway inflammation in lipopolysaccharide-stimulated RAW 264.7 cells and ovalbumin-induced hyper-responsiveness mouse model.

Phlomoides umbrosa Turczaninow (PU), a traditional Korean medicinal herb, exhibits osteogenic and anti-inflammatory effects. This research explored the effect of PU extracts on hyperimmune responses within the respiratory tract using lipopolysaccharide-stimulated RAW 264.7 cells and an ovalbumin-induced hyper-responsiveness model. The inflammatory cytokines, protein expression linked to airway inflammation, antioxidant enzyme activity, histopathological observation, and expectorant activity were measured. The results revealed that PU treatment led to a concentration-dependent reduction in Th2 cytokines and the expression of nuclear factor (NF)-κB, phosphatase-tensin homolog, mitogen-activated protein kinase (MAPK), and inducible nitric oxide synthase (iNOS). Simultaneously, antioxidant enzyme activity increased. Furthermore, PU exhibited substantial enhancements in lung tissue condition and expectorant activity relative to the allergic rhinitis-induced group. These findings indicate the potential of PU to mitigate airway inflammation and excessive mucus production by suppressing NF-κB, MAPK, and iNOS pathways. Consequently, PU emerges as a promising anti-inflammatory agent for respiratory tract applications. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-024-01521-3.

Utility of F-18 FDG-PET in detecting primary aldosteronism in patients with bilateral adrenal incidentalomas.

In patients with primary aldosteronism who have bilateral adrenal incidentalomas, it is important to identify which adrenal gland is secreting excess aldosterone. Traditionally, adrenal vein sampling (AVS) has been performed for lateralization despite its invasiveness. Here we report a case of bilateral adrenal incidentaloma in which 18-Fluorodeoxyglucose (FDG)-positron emission tomography (PET) was used to identify the functional adrenal mass. A 53-yr-old man was referred to our clinic due to bilateral adrenal incidentalomas (right: 1 cm, left: 2.5 cm) on computed tomography (CT). Given his history of colon cancer, FDG-PET/CT scanning was used to rule out metastasis. Although there was focal hot uptake lesion in the right adrenal gland, the patient was suspected primary aldosteronism clinically more than metastasis because of the patient's underlying hypertension with hypokalemia. It was consistent with the results of AVS. Based on these findings, we propose that FDG-PET/CT can be used instead of AVS to identify the source of primary aldosteronism between two bilateral adrenal incidentalomas.

Osteopontin levels in patients with papillary thyroid cancer according to the presence of Hashimoto's thyroiditis.

BACKGROUND: Human papillary thyroid carcinoma (PTC) is often associated with Hashimoto's thyroiditis (HT); their coexistence improves PTC prognosis. Osteopontin, a secreted glycoprotein, plays a role in cell survival, immunity, and tumor progression, its expression being associated with a poor prognosis and metastasis in several malignancies. Osteopontin overexpression correlates with aggressive clinicopathological features in PTC. Lymph node metastases and large tumor size positively correlate with osteopontin positivity. This study aimed to: (1) confirm osteopontin overexpression in human PTC samples; (2) compare osteopontin expression levels in PTC cases with and without HT; and (3) identify correlations between tumor aggressiveness and osteopontin expression levels. MATERIALS AND METHODS: Plasma osteopontin was assessed in 45 patients with PTC, 22 patients with PTC and HT, and 24 healthy controls by enzyme-linked immunosorbent assay. Thyroid tissue osteopontin mRNA and protein levels were analyzed by reverse transcription-polymerase chain reaction and Western blotting, respectively. RESULTS: Plasma osteopontin levels were significantly higher in PTC patients than in healthy controls. Plasma osteopontin, tissue osteopontin mRNA, and tissue osteopontin protein levels were significantly lower in patients with PTC and HT than in those with PTC alone. In advanced disease stage cases, osteopontin mRNA and protein expression levels were lower in patients with PTC and HT than in those with PTC alone. However, the osteopontin expression level was not significantly associated with the TNM stage. CONCLUSIONS: Plasma osteopontin, tissue osteopontin mRNA, and tissue osteopontin protein levels were significantly lower in patients with PTC and HT than in those with PTC alone, suggesting that HT attenuates PTC aggressiveness through negative regulation of osteopontin expression.

Acute and 28-Day Subacute Toxicity Studies of Hexane Extracts of the Roots of Lithospermum erythrorhizon in Sprague-Dawley Rats.

Lithospermum erythrorhizon has long been used as a traditional oriental medicine. In this study, the acute and 28-day subacute oral dose toxicity studies of hexane extracts of the roots of L. erythrorhizon (LEH) were performed in Sprague-Dawley rats. In the acute toxicity study, LEH was administered once orally to 5 male and 5 female rats at dose levels of 500, 1,000, and 2,000 mg/kg. Mortality, clinical signs, and body weight changes were monitored for 14 days. Salivation, soft stool, soiled perineal region, compound-colored stool, chromaturia and a decrease in body weight were observed in the extract-treated groups, and no deaths occurred during the study. Therefore, the approximate lethal dose (ALD) of LEH in male and female rats was higher than 2,000 mg/kg. In the subacute toxicity study, LEH was administered orally to male and female rats for 28 days at dose levels of 25, 100, and 400 mg/kg/day. There was no LEH-related toxic effect in the body weight, food consumption, ophthalmology, hematology, clinical chemistry and organ weights. Compound-colored (black) stool, chromaturia and increased protein, ketone bodies, bilirubin and occult blood in urine were observed in the male and female rats treated with the test substance. In addition, the necropsy revealed dark red discoloration of the kidneys, and the histopathological examination showed presence of red brown pigment or increased hyaline droplets in the renal tubules of the renal cortex. However, there were no test substance-related toxic effects in the hematology and clinical chemistry, and no morphological changes were observed in the histopathological examination of the kidneys. Therefore, it was determined that there was no significant toxicity because the changes observed were caused by the intrinsic color of the test substance. These results suggest that the no-observed-adverse-effect Level (NOAEL) of LEH is greater than 400 mg/kg/day in both sexes.

Case of bronchoesophageal fistula with gastric perforation due to multidrug-resistant tuberculosis.

Gastric perforation and tuberculous bronchoesophageal fistula (TBEF) are very rare complications of extrapulmonary tuberculosis (TB). We present a case of pulmonary TB with TBEF and gastric perforation caused by a multidrug-resistant tuberculosis strain in a non-acquired immune deficiency syndrome male patient. The patient underwent total gastrectomy with Roux-en-Y end-to-side esophagojejunostomy and feeding jejunostomy during intravenous treatment with anti-TB medication, and esophageal reconstruction with colonic interposition and jejunocolostomy were performed successfully after a full course of anti-TB medication. Though recent therapies for TBEF have favored medication, patients with severe stenosis or perforation require surgery and medication with anti-TB drugs based upon adequate culture and drug susceptibility testing.

Curcumin Enhances Docetaxel-Induced Apoptosis of 8505C Anaplastic Thyroid Carcinoma Cells.

BACKGROUND: Anaplastic thyroid cancer (ATC) is one of the most aggressive malignancies in humans, and its progression is poorly controlled by existing therapeutic methods. Curcumin has been shown to suppress inflammation and angiogenesis. In this study, we evaluated whether curcumin could augment docetaxel-induced apoptosis of ATC cells. We also analyzed changes in nuclear factor κB (NF-κB) and cyclooxygenase-2 (COX-2) expression levels to delineate possible mechanisms of their combined action. METHODS: ATC cells were cultured and treated with curcumin and docetaxel alone or in combination. The effects on cell viability were determined by MTS assay. Apoptosis was assessed by annexin V staining and confirmed by flow cytometric analysis. Caspase, COX-2, NF-κB levels were assayed by Western blotting. RESULTS: Curcumin combined with docetaxel led to lower cell viability than treatment with docetaxel or curcumin alone. Annexin V staining followed by flow cytometric analysis demonstrated that curcumin treatment enhanced the docetaxel-induced apoptosis of ATC cells. Additionally, curcumin inhibited docetaxel-induced p65 activation and COX-2 expression. CONCLUSION: We conclude that curcumin may enhance docetaxel's antitumor activity in ATC cells by interfering with NF-κB and COX-2. Our results suggest that curcumin may emerge as an attractive therapeutic candidate to enhance the antitumor activity of taxanes in ATC treatment.

Neuroprotective effects of a traditional herbal prescription on transient cerebral global ischemia in gerbils.

AIM OF THE STUDY: Kyung-Ok-Ko (KOK), a traditional herbal prescription composed of Rehmannia glutinosa var. purpurae, Panax ginseng, Poria cocos, Lycium chinense, Aquillaria agallocha and honey, has been used to treat age-related symptoms, such as amnesia or dementia, and has been shown to ameliorate scopolamine-induced memory impairment in mice. However, the effects of KOK on transient cerebral global ischemia-induced brain damage are unclear. MATERIALS AND METHODS: Transient cerebral global ischemia was induced by occluding the bilateral common carotid artery for 5 min followed by reperfusion for 7 days. KOK (0.25, 0.5, 1, or 2 g/kg) was administered orally immediately after reperfusion and once a day over the next 7 days. Y-maze or novel object recognition tasks were to analyze learning and memory capabilities at 4 or 5 days after reperfusion, respectively. Histochemistry and immunohistochemistry were used for evaluation of the effect of KOK on neuronal degeneration. RESULTS: Histochemical studies showed that KOK increased the number of viable cells detected by Nissl staining and decreased the number of degenerated neuronal cells detected by Fluoro-Jade B staining in the hippocampal CA1 region. In the immunohistochemical study, the sub-chronic KOK administration attenuated the ischemia-induced activation of microglia and astrocytes and the increase of cytokine IL-1ß (P<0.05). In addition, KOK administration significantly attenuated the ischemia-induced cognitive impairments observed in the Y-maze and novel object recognition tasks (P<0.05). CONCLUSION: These findings suggest that the neuroprotective effects of KOK may be mediated by its anti-inflammatory activities, resulting in the attenuation of memory impairment.

The effect of external beam radiotherapy volume on locoregional control in patients with locoregionally advanced or recurrent nonanaplastic thyroid cancer.

PURPOSE: We evaluated outcomes of patients treated with external beam radiotherapy (EBRT) for locoregionally advanced or recurrent nonanaplastic thyroid cancer and analyzed the effect of EBRT volume on locoregional control. METHODS: This study included 23 patients with locoregionally advanced or recurrent nonanaplastic thyroid cancer who were treated with EBRT. Two different EBRT target volumes were executed as follows: 1) limited field (LF, n = 11) included the primary (involved lobe) or recurrent tumor bed and the positive nodal area; 2) elective field (EF, n = 12) included the primary (involved lobe) or recurrent tumor bed and the regional nodal areas in the cervical neck and upper mediastinum. Clinical parameters, such as gender, age, histologic type, recurrence, stage, thyroglobulin level, postoperative residuum, radioiodine treatment, and EBRT volume were analyzed to identify prognostic factors associated with locoregional control. RESULTS: There were no significant differences in the clinical parameter distributions between the LF and EF groups. In the LF group, six (55%) patients developed locoregional recurrence and three (27%) developed distant metastasis. In the EF group, one (8%) patient developed locoregional recurrence and one (8%) developed a distant metastasis. There was a significant difference in locoregional control rate at 5 years in the LF and EF groups (40% vs. 89%, p = 0.041). There were no significant differences in incidences of acute and late toxicities between two groups (p >0.05). CONCLUSIONS: EBRT with EF provided significantly better locoregional control than that of LF; however, further larger scaled studies are warranted.

A case of constrictive pericarditis associated with huge epicardial fat volume.

Massive deposits of fat around heart are seen in overweight persons and are associated with coronary artery disease. Investigators have focused on the clinical significance of epicardial fat with respect to metabolic effects such as insulin resistance and inflammation, but the mechanical effects, such as constriction, have been largely ignored. We present an unusual case of a 59-year-old woman with obesity and diabetes mellitus who had been undergoing peritoneal dialysis due to end-stage renal disease, and who developed constrictive pericarditis, possibly secondary to extensive epicardial fatty accumulation.