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Journal of Ethnopharmacology Oct 2023Herb-induced liver injury is poorly described for African herbal remedies, such as Acokanthera oppositifolia. Although a commonly used treatment for pain, snake bites...
ETHNOPHARMACOLOGICAL RELEVANCE
Herb-induced liver injury is poorly described for African herbal remedies, such as Acokanthera oppositifolia. Although a commonly used treatment for pain, snake bites and anthrax, it is also a well-known arrow poison, thus toxicity is to be expected.
AIM OF THE STUDY
The cytotoxicity and preliminary mechanisms of toxicity in HepG2 hepatocarcinoma cells were assessed.
MATERIALS AND METHODS
The effect of hot water and methanol extracts were on cell density, oxidative status, mitochondrial membrane potential, fatty acids, caspase-3/7 activity, adenosine triphosphate levels, cell cycling and viability was assessed. Phytochemicals were tentatively identified using ultra-performance liquid chromatography.
RESULTS
The hot water extract displayed an IC of 24.26 μg/mL, and reduced proliferation (S- and G2/M-phase arrest) and viability (by 30.71%) as early as 24 h after incubation. The methanol extract had a comparable IC of 26.16 μg/mL, and arrested cells in the G2/M-phase (by 18.87%) and induced necrosis (by 13.21%). The hot water and methanol extracts depolarised the mitochondrial membrane (up to 0.84- and 0.74-fold), though did not generate reactive oxygen species. The hot water and methanol extracts decreased glutathione (0.42- and 0.62-fold) and adenosine triphosphate (0.08- and 0.26-fold) levels, while fatty acids (2.00- and 4.61-fold) and caspase-3/7 activity (1.98- and 5.82-fold) were increased.
CONCLUSION
Extracts were both cytostatic and cytotoxic in HepG2 cells. Mitochondrial toxicity was evident and contributed to reducing adenosine triphosphate production and fatty acid accumulation. Altered redox status perturbed proliferation and promoted necrosis. Extracts of A. oppositifolia may thus promote necrotic cell death, which poses a risk for inflammatory hepatotoxicity with associated steatosis.
Topics: Humans; Hep G2 Cells; Methanol; Cytostatic Agents; Caspase 3; Plant Extracts; Carcinoma, Hepatocellular; Antineoplastic Agents; Necrosis; Liver Neoplasms; Water; Apocynaceae; Adenosine Triphosphate; Apoptosis
PubMed: 37182674
DOI: 10.1016/j.jep.2023.116617 -
Scientific Reports Jan 2024The COVID-19 pandemic has substantially affected people and healthcare systems. One of the main challenges was the reduction and change in the pattern of non-COVID-19...
The COVID-19 pandemic has substantially affected people and healthcare systems. One of the main challenges was the reduction and change in the pattern of non-COVID-19 diseases and conditions. Moreover, due to the mental burden of the pandemic, the trend of poisonings and abuses changed. In this study, we aimed to assess the trends of poisonings from different agents before and during the COVID-19 pandemic using the interrupted time series method. This study was conducted at one of the main Tehran referral centers for poisoning, Baharloo Hospital. Pre-COVID-19 period was defined as April 2018 to January 2020 while the COVID-19 time was from February 2020 to March 2022. The total number of monthly poisoning cases in addition to eight categories of drugs/substances/agents were identified, including drugs (such as psychiatric drugs, cardiovascular drugs, and analgesics), opioids, stimulants, methanol, ethanol, cannabis, pesticides, and carbon monoxide. Interrupted time series analysis was performed to compare the pre-pandemic trend of total monthly cases from each category in addition to the proportion (%) of each one. In total, 13,020 cases were poisoned during the study period, among which 6088 belonged to the pre-pandemic period and 6932 were admitted during the COVID-19 era. There was no significant difference in terms of demographic characteristics of patients before and during the pandemic (p-value > 0.05). At the beginning of the pandemic, there was a sudden fall in the number of poisoning patients (- 77.2 cases/month, p-value = 0.003), however, there was a significant increasing trend during the COVID time (3.9 cases/month, p-value = 0.006). Most of the categories had a sharp decrease at the beginning of the pandemic except for methanol and ethanol which had increases, although not significant. Cannabis also had a significant change in slope (- 0.6 cases/month, p-value = 0.016), in addition to the sudden decrease at the beginning of the pandemic (- 10 cases/month, p-value = 0.007). Regarding the proportion of each category from total monthly poisoning cases, methanol, and ethanol had immediate rises of 4.2% per month and 10.1% per month, respectively (both significant). The pandemic had significant effects on the pattern of poisonings from different agents in Iran, the most important of which were alcohol (ethanol and methanol). These differences had policy implications that can be helpful for policymakers and healthcare systems in combating similar situations in the future.
Topics: Humans; COVID-19; Methanol; Pandemics; Iran; Ethanol; Cannabis; Hallucinogens; Cannabinoid Receptor Agonists
PubMed: 38267612
DOI: 10.1038/s41598-024-52537-y -
Current Opinion in Biotechnology Feb 2024Single-carbon (C1) biorefinery plays a key role in the consumption of global greenhouse gases and a circular carbon economy. Thereby, we have focused on the valorization... (Review)
Review
Single-carbon (C1) biorefinery plays a key role in the consumption of global greenhouse gases and a circular carbon economy. Thereby, we have focused on the valorization of C1 compounds (e.g. methanol, formaldehyde, and formate) into multicarbon products, including bioplastic monomers, glycolate, and ethylene glycol. For instance, methanol, derived from the oxidation of CH, can be converted into glycolate, ethylene glycol, or erythrulose via formaldehyde and glycolaldehyde, employing C1 and/or C2 carboligases as essential enzymes. Escherichia coli was engineered to convert formate, produced from CO via CO or from CO directly, into glycolate. Recent progress in the design of biotransformation pathways, enzyme discovery, and engineering, as well as whole-cell biocatalyst engineering for C1 biorefinery, was addressed in this review.
Topics: Methanol; Carbon; Carbon Dioxide; Ethylene Glycol; Escherichia coli; Formates; Formaldehyde; Glycolates
PubMed: 38128199
DOI: 10.1016/j.copbio.2023.103047 -
PloS One 2023Pomegranate (Punica granatum) peels have shown numerous health benefits such as antioxidant, anti-inflammatory, and antimicrobial activities. These health activities are...
Pomegranate (Punica granatum) peels have shown numerous health benefits such as antioxidant, anti-inflammatory, and antimicrobial activities. These health activities are owed to the unique phytochemical components present in pomegranate peels. Variations in the pomegranate cultivar, geographical region, and extraction methods significantly affect the phytochemical composition and concentrations of pomegranate fruits and their peels, hence their health outcomes. Therefore, this study aimed to examine the phytochemical contents of pomegranate peels of Jordanian origin and their antioxidant and antimicrobial activities. Among the 6 extracts of pomegranate peels tested, the ethanol extract exhibited the highest total phenolic content (TPC = 297.70 ± 1.73 mg GAE/g DW), highest total flavonoids content (TFC = 116.08 ± 3.46 mg RE/g DW), highest hydrolyzable tannins (HT) contents (688.50 ± 3.54 mg TE/g DW). Whereas the highest condensed tannins (CT) content was found in both the ethanol (13.87 ± 0.58 mg CE/g DW) and methanol (13.84 ± 0.55 mg CE/g DW) extracts. For the antioxidant activities, the water extract of pomegranate peels displayed the highest inhibitory effect on DPPH radicals (9.43 ± 0.06 μmole TE/g DW), while for the ABTS+ assay the methanol and ethanol extracts exhibited the highest activities of 11.09 ± 0.02 and 11.09 ± 0.06 μmole TE/g DW, respectively. For the FRAP assay, the aqueous methanol extract exhibited the highest reducing activity (1.60 ± 0.09 mmole Fe (II)/g DW). As for the antimicrobial activities of various extracts of pomegranate peels, the highest antimicrobial activity against Micrococcus luteus was achieved by the ethanol extract (MIC = 6.25 mg/mL), whereas the lowest antimicrobial activity was observed against Candida krusei using the methanol extract (MIC = 100 mg/mL). These results indicate that pomegranate peels of Jordanian origin are rich in phytochemical content and exhibited strong antioxidant and antimicrobial activities making these agroindustrial by-products potential candidates for various medical applications and possible safe sources for important bioactive components.
Topics: Antioxidants; Fruit; Pomegranate; Plant Extracts; Jordan; Methanol; Phytochemicals; Ethanol; Anti-Infective Agents
PubMed: 38032959
DOI: 10.1371/journal.pone.0295129 -
Molecules (Basel, Switzerland) Nov 2023The search for potent antimicrobial compounds is critical in the face of growing antibiotic resistance. This study explores Poepp. (), a Caribbean plant traditionally...
The search for potent antimicrobial compounds is critical in the face of growing antibiotic resistance. This study explores Poepp. (), a Caribbean plant traditionally used for disease treatment. The dried plant powder was subjected to successive extractions using different solvents: hexane (F1), dichloromethane (F2), methanol (F3), a 50:50 mixture of methanol and water (F4), and water (F5). Additionally, a parallel extraction was conducted using a 50:50 mixture of methanol and chloroform (F6). All the fractions were evaluated for their antimicrobial activity, and the F6 fraction was characterized using untargeted metabolomics using SPME-GC×GC-TOFMS. The extracts of F3, F4, and F5 showed antibacterial activity against ATCC 25923 (5 mg/mL), MRSA BA22038 (5 mg/mL), and ATCC 27853 (10 mg/mL), and fraction F6 showed antibacterial activity against ATCC 29213 (2 mg/mL), ATCC 25922 (20 mg/mL), ATCC 27853 (10 mg/mL), ATCC 29212 (10 mg/mL), 024 (2 mg/mL), and 003 (2 mg/mL). Metabolomic analysis of F6 revealed 2861 peaks with 58 identified compounds through SPME and 3654 peaks with 29 identified compounds through derivatization. The compounds included methyl ester fatty acids, ethyl ester fatty acids, terpenes, ketones, sugars, amino acids, and fatty acids. This study represents the first exploration of metabolomics and its antimicrobial potential, providing valuable insights for plant classification, phytochemical research, and drug discovery.
Topics: Acalypha; Methanol; Microbial Sensitivity Tests; Anti-Bacterial Agents; Anti-Infective Agents; Fatty Acids; Esters; Water; Plant Extracts
PubMed: 38067611
DOI: 10.3390/molecules28237882 -
Current Opinion in Biotechnology Aug 2023Methanol is a promising feedstock for industrial bioproduction: it can be produced renewably and has high solubility and limited microbial toxicity. One of the key... (Review)
Review
Methanol is a promising feedstock for industrial bioproduction: it can be produced renewably and has high solubility and limited microbial toxicity. One of the key challenges for its bio-industrial application is the first enzymatic oxidation step to formaldehyde. This reaction is catalysed by methanol dehydrogenases (MDH) that can use NAD, O or pyrroloquinoline quinone (PQQ) as an electron acceptor. While NAD-dependent MDH are simple to express and have the highest energetic efficiency, they exhibit mediocre kinetics and poor thermodynamics at ambient temperatures. O-dependent methanol oxidases require high oxygen concentrations, do not conserve energy and thus produce excessive heat as well as toxic HO. PQQ-dependent MDH provide a good compromise between energy efficiency and good kinetics that support fast growth rates without any drawbacks for process engineering. Therefore, we argue that this enzyme class represents a promising solution for industry and outline engineering strategies for the implementation of these complex systems in heterologous hosts.
Topics: NAD; Methanol; Hydrogen Peroxide; PQQ Cofactor; Bioengineering
PubMed: 37320962
DOI: 10.1016/j.copbio.2023.102953 -
Molecular Pharmaceutics Nov 2023The antiparasitic drug niclosamide (NCL) is notable for its ability to crystallize in multiple 1:1 channel solvate forms, none of which are isostructural. Here, using a...
The antiparasitic drug niclosamide (NCL) is notable for its ability to crystallize in multiple 1:1 channel solvate forms, none of which are isostructural. Here, using a combination of time-resolved synchrotron powder X-ray diffraction and thermogravimetry, the process-induced desolvation mechanisms of methanol and acetonitrile solvates are investigated. Structural changes in both solvates follow a complicated molecular-level trajectory characterized by a sudden shift in lattice parameters several degrees below the temperature where the desolvated phase first appears. Model fitting of kinetic data obtained under isothermal heating conditions suggests that the desolvation is rate-limited by the nucleation of the solvent-free product. The desolvation pathways identified in these systems stand in contrast to previous investigations of the NCL channel hydrate, where water loss by diffusion initially yields an anhydrous isomorph that converts to the thermodynamic polymorph at significantly higher temperatures. Taking the view that each solvate lattice is a unique "pre-organized" precursor, a comparison of the pathways from different starting topologies to the same final product provides the opportunity to reevaluate assumptions of how various factors (e.g., solvent binding strength, density) influence solid-state desolvation processes.
Topics: Niclosamide; X-Ray Diffraction; Solvents; Water; Methanol
PubMed: 37850910
DOI: 10.1021/acs.molpharmaceut.3c00481 -
Scientific Reports Sep 2023Soy leghemoglobin is one of the most important and key ingredients in plant-based meat substitutes that can imitate the colour and flavour of the meat. To improve the...
Soy leghemoglobin is one of the most important and key ingredients in plant-based meat substitutes that can imitate the colour and flavour of the meat. To improve the high-yield production of leghemoglobin protein and its main component-heme in the yeast Pichia pastoris, glycerol and methanol cultivation conditions were studied. Additionally, in-silico metabolic modelling analysis of growth-coupled enzyme quantity, suggests metabolic gene up/down-regulation strategies for heme production. First, cultivations and metabolic modelling analysis of P. pastoris were performed on glycerol and methanol in different growth media. Glycerol cultivation uptake and production rates can be increased by 50% according to metabolic modelling results, but methanol cultivation-is near the theoretical maximum. Growth-coupled metabolic optimisation results revealed the best feasible upregulation (33 reactions) (1.47% of total reactions) and 66 downregulation/deletion (2.98% of total) reaction suggestions. Finally, we describe reaction regulation suggestions with the highest potential to increase heme production yields.
Topics: Glycerol; Leghemoglobin; Methanol; Heme
PubMed: 37739976
DOI: 10.1038/s41598-023-42865-w -
Microbial Cell Factories Jul 2023Ablynx NV, a subsidiary of Sanofi, has a long-standing focus on the development of Nanobody® molecules as biopharmaceuticals (Nanobody® is a registered trademark of...
BACKGROUND
Ablynx NV, a subsidiary of Sanofi, has a long-standing focus on the development of Nanobody® molecules as biopharmaceuticals (Nanobody® is a registered trademark of Ablynx NV). Nanobody molecules are single variable domains, and they have been met with great success part due to their favorable expression properties in several microbial systems. Nevertheless, the search for the host of the future is an ongoing and challenging process. Komagataella phaffi (Pichia pastoris) is one of the most suitable organisms to produce Nanobody molecules. In addition, genetic engineering of Pichia is easy and an effective approach to improve titers.
RESULTS
Here we report that P. pastoris engineered to co-express genes encoding four auxiliary proteins (HAC1, KAR2, PDI and RPP0), leads to a marked improvement in the expression of Nanobody molecules using the AOX1 methanol induction system. Titer improvement is mainly attributed to HAC1, and its beneficial effect was also observed in a methanol-free expression system.
CONCLUSION
Our findings are based on over a thousand fed-batch fermentations and offer a valuable guide to produce Nanobody molecules in P. pastoris. The presented differences in expressability between types of Nanobody molecules will be helpful for researchers to select both the type of Nanobody molecule and Pichia strain and may stimulate further the development of a more ecological methanol-free expression platform.
Topics: Saccharomycetales; Pichia; Biological Products; Fermentation; Methanol
PubMed: 37481525
DOI: 10.1186/s12934-023-02132-z -
Alcohol (Fayetteville, N.Y.) Dec 2023Methyl alcohol intoxication causes severe morbidity and mortality, especially in developing countries. Formic acid is formed as a result of methanol metabolism. Formic...
BACKGROUND AND AIM
Methyl alcohol intoxication causes severe morbidity and mortality, especially in developing countries. Formic acid is formed as a result of methanol metabolism. Formic acid accumulation and inhibition of adenosine triphosphate synthesis result in ophthalmic issues. This study aimed to demonstrate that the optic nerve sheath diameter (ONSD) measurement is an accurate prognostic marker and can be helpful in the diagnosis of methanol intoxication.
MATERIALS AND METHODS
This prospective study was conducted with 52 patients who were admitted to the emergency department after alcohol consumption and agreed to participate in the study. Age, gender, comorbid diseases, vital signs, ONSD ultrasonography measurements, hospitalization and discharge status, in-hospital mortality status, dialysis need, presence of visual impairment, blood gas parameters, respiratory status, time since alcohol intake, ethanol levels, urea levels, and creatinine levels were analyzed.
RESULTS
ROC curve analysis was performed to evaluate the predictive power of ONSD to diagnose methanol intoxication. The area under the curve was 0.857 for the cut-off value of 5.05 mm (95 % CI: 0.728-0.985; p < 0.001), with a sensitivity of 80.8 % and a specificity of 100 %. In the regression analysis performed to determine the prognostic value of the parameters in estimating mortality in methanol intoxication cases, an increase in ONSD (OR: 3.619; 95 % CI: 0.057-0.199; p = 0.001), an increase in lactate levels (OR: 5.653; 95 % CI: 0.040-0.085; p < 0.001), and increased duration after alcohol intake (OR: 2558; 95 % CI: 0.004-0.034; p = 0.014) were identified as independent predictors of mortality, but pH, HCO, and base deficit levels were not significant predictors.
CONCLUSIONS
We believe that ONSD can be helpful for the differential diagnosis and prognosis of patients with suspected methanol toxicity who presented with alcohol intake.
Topics: Humans; Methanol; Prospective Studies; Optic Nerve; ROC Curve
PubMed: 37481045
DOI: 10.1016/j.alcohol.2023.06.002