Identification of a novel aromatic-turmerone analog that activates chaperone-mediated autophagy through the persistent activation of p38.

Introduction: Aromatic (Ar)-turmerone is a bioactive component of turmeric oil obtained from Curcuma longa. We recently identified a novel analog (A2) of ar-turmerone that protects dopaminergic neurons from toxic stimuli by activating nuclear factor erythroid 2-related factor 2 (Nrf2). D-cysteine increases Nrf2, leading to the activation of chaperone-mediated autophagy (CMA), a pathway in the autophagy-lysosome protein degradation system, in primary cultured cerebellar Purkinje cells. In this study, we attempted to identify novel analogs of ar-turmerone that activate Nrf2 more potently and investigated whether these analogs activate CMA. Methods: Four novel analogs (A4-A7) from A2 were synthesized. We investigated the effects of A2 and novel 4 analogs on Nrf2 expression via immunoblotting and CMA activity via fluorescence observation. Results: Although all analogs, including A2, increased Nrf2 expression, only A4 activated CMA in SH-SY5Y cells. Additionally, A4-mediated CMA activation was not reversed by Nrf2 inhibition, indicating that A4 activated CMA via mechanisms other than Nrf2 activation. We focused on p38, which participates in CMA activation. Inhibition of p38 significantly prevented A4-mediated activation of CMA. Although all novel analogs significantly increased the phosphorylation of p38 6 h after drug treatment, only A4 significantly increased phosphorylation 24 h after treatment. Finally, we revealed that A4 protected SH-SY5Y cells from the cytotoxicity of rotenone, and that this protection was reversed by inhibiting p38. Conclusion: These findings suggest that the novel ar-turmerone analog, A4, activates CMA and protects SH-SY5Y cells through the persistent activation of p38.

Synthesis of Selenoesters via Aldol Condensation and/or Conjugate Reduction and Their Antiviral Activities.

A variety of unsaturated selenoesters (including phenolic ones) were produced in good to high yields and with high E/Z ratios using TiCl4-promoted aldol condensation between Se-phenyl selenoacetate and their respective aldehydes without aqueous workup. A representative phenolic unsaturated selenoester was applied to acylation of tyrosine methyl ester without protection of the phenolic hydroxy groups to furnish the corresponding amino acid conjugate. The conjugate reduction of the unsaturated selenoesters including phenolic ones and selenocoumarin with HSiEt3 was catalyzed by B(C6F5)3 to afford the corresponding saturated selenoesters in good to high yields. This method was also applicable to the reduction of a saturated selenoester to the corresponding O-silyl hemiselenoacetal in a high yield. Moreover, most acyclic unsaturated selenoesters were found to show good multiple antiviral activities against HIV-1, HBV, and SARS-CoV-2.

Acute uterine inversion following an induced abortion.

Acute uterine inversion is a rare and potentially life-threatening obstetric emergency. Its occurrence as a result of a mid-trimester abortion is an even rarer consequence. We report a case of a 32-year-old woman who presented with complete acute uterine inversion and hemorrhagic shock following an incomplete medical abortion at 14 weeks of gestation. Our attempts at non-operative reversal of the inversion failed. Therefore, we resorted to the manual replacement of the uterus via laparotomy without using surgical instruments or an incision in the cervical ring. The laparotomic manual replacement served as a successful alternative with minimal immediate or long-term morbidity that may have resulted from trauma and scarring of the uterus.

Identification of molecular determinants of antibiotic resistance in some fish farms of Ghana.

Antimicrobial resistance is a global health challenge caused by the ability of microorganisms including bacteria, fungi, protozoans and viruses to survive the effects of drugs that hitherto were effective against them. This study sought to investigate the presence of antibiotic-resistant bacteria and their corresponding molecular determinants in fish farms of the Central and Western Regions of Ghana. Management practices and antibiotic use at the fish farms were obtained through the administration of a questionnaire. Coliform and Gram-positive bacterial loads of catfish (Clarias gariepinus), tilapia (Oreochromis niloticus) intestinal microbiota, and pond water samples recovered on MacConkey Agar and Mannitol Salt Agar were determined. Bacterial isolates were identified using various biochemical assays. Antibiotic resistance profiles and possible responsible genes of bacterial isolates were determined using the disc diffusion and Polymerase Chain Reaction (PCR) methods respectively. The study revealed that none of the fish farm managers admitted using antibiotics for prevention and treatment of diseases and no major disease outbreak had ever been recorded. Bacterial loads of pond water exceeded the acceptable level of ≤100 E. coli and <10 coliforms per mL for wastewater recommended for use in fish farming. In all, 145 bacterial isolates comprising 99 Gram negative and 46 Gram-positive bacteria were stored and identified. Most isolates were resistant to at least an antibiotic. Both Gram-negative and Gram-positive bacteria were highly resistant to beta-lactam antibiotics with a corresponding high percentage detection of the bla TEM gene compared to other classes of antibiotics. This study has revealed the presence of various molecular determinants of antibiotic resistance including bla TEM, cmIA, qnrS, tetB and bla CTX-M, in multidrug-resistant bacteria at some fish farms in Ghana. There is the need to increase awareness about risks associated with the misuse and overuse of antibiotics by humans and the potential risk of spread of multi-drug resistant-bacteria in the environment.

Health risk and source assessment of semi-volatile phenols, p-chloroaniline and plasticizers in plastic packaged (sachet) drinking water.

The presence of U.S. EPA priority organic contaminants in drinking water poses a dire health risk on consumers. Packaged drinking water such as plastic sachet drinking water has significantly gained market in both developed and developing countries, especially, its dominance in the Ghanaian market. The treatment process, packaging, and storage of the sachet drinking water contribute to the levels of genotoxic semi-volatile phenols, p-chloroaniline, and plasticizers contamination in the drinking water. The study thus sought to investigate the levels of semi-volatile phenols, p-chloroaniline, and plasticizer contaminants in sachet drinking water on the Ghanaian market and the associated health risk of exposure. The study also investigated the possible sources of the contaminants. A total of thirty (30) different brands of sachet water on the Ghanaian market were studied. The samples were extracted in replicates (n = 3) using Solid Phase Extraction (SPE) cartridges and further analysed with GC-MS (SIM mode). The source apportionment was conducted using absolute principal component analysis coupled with multiple, linear regression (APCA-MLR) and automatic linear regression (APCA-MALR) modelling. The mean total levels for the phenols, p-chloroaniline, and plasticizers were between 210.2 and 18,914.9, 11.2 and 18,871.0, and 21.2 and 69,834.1 ng/L respectively. The cumulative non-cancer risk (hazard quotient) and cancer risk upon exposure were computed to range between 2.1 × 10-3 and 1.2 and 1.5 × 10-7 and 1.3 × 10-4 respectively. About 37% of the samples had elevated cancer risk (>10-6) which may contribute to the existing incidence, cause for concern. The five sources found for the contaminants were apportioned as "environmental background (major)", "water treatment/disinfectant", "plastic/plasticizers", "storage and preservation", and "residual inter-conversion/degradation sources".

Aromatic-Turmerone Analogs Protect Dopaminergic Neurons in Midbrain Slice Cultures through Their Neuroprotective Activities.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra. The inflammatory activation of microglia participates in dopaminergic neurodegeneration in PD. Therefore, chemicals that inhibit microglial activation are considered to have therapeutic potential for PD. Aromatic (ar)-turmerone is a main component of turmeric oil extracted from Curcuma longa and has anti-inflammatory activity in cultured microglia. The aims of the present study are (1) to investigate whether naturally occurring S-enantiomer of ar-turmerone (S-Tur) protects dopaminergic neurons in midbrain slice cultures and (2) to examine ar-turmerone analogs that have higher activities than S-Tur in inhibiting microglial activation and protecting dopaminergic neurons. R-enantiomer (R-Tur) and two analogs showed slightly higher anti-inflammatory effects in microglial BV2 cells. S- and R-Tur and these two analogs reversed dopaminergic neurodegeneration triggered by microglial activation in midbrain slice cultures. Unexpectedly, this neuroprotection was independent of the inhibition of microglial activation. Additionally, two analogs more potently inhibited dopaminergic neurodegeneration triggered by a neurotoxin, 1-methyl-4-phenylpyridinium, than S-Tur. Taken together, we identified two ar-turmerone analogs that directly and potently protected dopaminergic neurons. An investigation using dopaminergic neuronal precursor cells suggested the possible involvement of nuclear factor erythroid 2-related factor 2 in this neuroprotection.

Primary osteosarcoma of the uterus: a report of two cases.

Primary extraskeletal osteosarcoma is an uncommon disease and has been reported to affect the uterus only rarely. Less than 20 cases have so far been reported in the English literature. The common clinical presentation is heavy bleeding per vaginam, and in virtually all cases, the diagnosis has been made at an advanced stage of the disease. Various authors have recommended adjuvant chemotherapy, but outcomes have so far been uniformly poor, with survival extended by months rather than years. We present two cases of this rare condition, which were diagnosed four months apart within our histopathology laboratory andconfirmed the very late presentation of the disease in one and the poor survival of both patients. Funding: None declared.

Multiple Antibiotic Resistance-Coliform Bacteria in Some Selected Fish Farms of the Central Region of Ghana.

This study aimed at assessing the quality of water and fishery products as well as the antibiotic resistance status of some selected fish farms of the Central Region of Ghana. Interview guides were administered to farmers to get data on farming practices and antibiotic use. Total coliform loads of catfish (Clarias gariepinus), tilapia (Oreochromis niloticus), and water samples were determined. Coliforms were identified through various biochemical assays, and their antibiotic resistance patterns were determined. Generally, the total coliform loads of water samples significantly surpassed those of fish samples (p < 0.05). The maximum and minimum antibiotic resistance percentages were recorded for ampicillin (96.83%) and gentamicin (6.35%), respectively. Although farmers stated that antibiotics were sparingly used, coliform bacteria isolated exhibited various antibiotic resistance patterns. Four out of six fish farms harboured some coliforms with multiple antibiotic resistance (MAR) indices above 0.2, an indication that these bacteria originated from potentially dangerous sources where antibiotics are regularly used.

Fast, easy, cheap, robust and safe method of analysis of Sudan dyes in chilli pepper powder.

Illicit use of Sudan dyes, a group of harmful and carcinogenic azo dyes, in the food industry has taken a surge in various parts of the world, especially in Africa. Their use in food as additives pose a dire health risk to consumers and have been banned by various food regulatory bodies worldwide. To help increase surveillance, various methods have been proposed for their analysis in literature. This study also sought to experiment and propose an alternative method for quick, easy, cheap, robust and ecologically safe analysis of Sudan dyes in chilli pepper powder and similar matrices. The optimized method used a 6.0 mL mixture of acetone:acetonitrile (1:5 v/v) solvent in a modified QuEChERs method for extraction of Sudan dyes I-IV. The simultaneous analysis of the dyes were achieved on Shimadzu prominence UFLC 20AD coupled with SPD 20AX UV detector operated at dual wavelength of 500 and 480 nm. A total of twenty four (24) chilli pepper powder samples from eight different vendors on the Ghana market were analysed using the optimized method. Quantitation of analytes were done using the external standard calibration method with determination coefficient, R2 > 0.9999. The limit of detection (LOD) and limit of quantitation (LOQ) of the method were 0.02-0.04 mg/kg and 0.05-0.13 mg/kg respectively. A good recovery range between 85.3 - 121.2% were obtained for a spike level of 1.0 mg/kg in real samples. ANOVA analysis at 95% CL showed statistically no significant difference (p > 0.05) in the recoveries between samples and also between the individual compounds. The method experimented and proposed in this study is fast, easy, cheap, robust and ecologically safe, presenting an alternative method for routine analysis for increased rate of surveillance against the illicit use of Sudan dyes as food additives.