Novel optical coherence tomography findings in a patient with methanol toxicity: a case report

ABSTRACT We report a case of acute methanol toxicity with unique optical coherence tomography findings. A 56-year-old man was referred to our ophthalmology clinic with a history of handmade vodka consumption and vision loss. On ophthalmologic examination, his vision was 20/100 in his right eye and 20/200 in his left eye. Bilateral mild optic disk hyperemia was detected on fundus examination. Because of the severity of systemic symptoms in such cases, it is very difficult to include optical coherence tomography in the ophthalmologic examination. However, we managed to perform optical coherence tomography and recorded shallow subretinal fluid and a prominent middle limiting membrane sign as acute retinal structural changes in the patient. The patient was treated with hemodialysis, intravenous ethanol, and sodium bicarbonate. On the fourth day of treatment, visual acuity improved to 20/20 in both eyes. In addition, the prominent middle limiting membrane sign and subretinal fluid disappeared. In this unusual case, retinal pigment epithelium damage and retinal ischemia may have contributed to the prominent middle limiting membrane and subretinal fluid, which are novel optical coherence tomography findings of methanol toxicity.

Intoxicación por metanol por consumo de bebidas alcohólicas adulteradas. Efectos en el sistema nervioso. Reporte de un caso / Methanol Poisoning by Consumption of Adulterated Alcoholic Beverages. Effects on the Nervous System. A Case Report

Resumen La intoxicación por metanol puede ocurrir de forma inadvertida por la ingesta de bebidas alcohólicas adulteradas. Se trata una entidad poco frecuente, sin embargo, se ha reportado un aumento en la incidencia durante la pandemia de COVID-19. La intoxicación con metanol representa una urgencia médica, ya que puede provocar daño severo en el sistema nervioso central y periférico, además de acidosis metabólica, daño renal agudo e incluso la muerte. En este artículo se presenta el caso de un paciente que cursó con intoxicación por metanol de manera inadvertida al consumir bebidas alcohólicas presumiblemente adulteradas. En el encéfalo se demostró necrosis hemorrágica de ambos núcleos putamen, además de cursar con neuritis óptica bilateral y polineuropatía periférica. Fue manejado con pulsos de esteroides intravenosos, con lo cual, mejoró significativamente su función visual, sensitiva y motora. En el presente caso no existieron complicaciones fatales y presentó una buena respuesta al tratamiento, sin embargo, el caso pone de relieve la necesidad de una mejor regulación en la producción y comercialización de bebidas alcohólicas en nuestro país, y, por otro lado, permite hacer a un llamado a los consumidores a tomar más precauciones en el consumo de bebidas alcohólicas de dudosa calidad o procedencia.

Abstract Methanol poisoning can occur unnoticed, by the ingestion of adulterated alcoholic beverages. In general, it is a rare entity, however, an increase in incidence has been reported during the SARS-CoV-2 pandemic. Methanol poisoning represents a medical emergency as it can cause severe damage to the central and peripheral nervous systems, as well as metabolic acidosis, acute kidney injury, and even death. This article presents the case of a patient who inadvertently developed methanol intoxication after consuming presumably adulterated alcoholic beverages. In the brain, hemorrhagic necrosis of both putamen nuclei was demonstrated, in addition to presenting with bilateral optic neuritis and peripheral polyneuropathy. He was managed with intravenous steroid pulses, which significantly improved his visual, sensory, and motor function. In the present case there were no fatal complications and presented a good response to treatment, however, the case highlights the need for better regulation in the production and marketing of alcoholic beverages in our country, and on the other hand, to invite consumers to take more precautions in the consumption of alcoholic beverages of dubious quality or origin.

Advances in biotransformation of methanol into chemicals / 生物工程学报

Methanol has become an attractive substrate for the biomanufacturing industry due to its abundant supply and low cost. The biotransformation of methanol to value-added chemicals using microbial cell factories has the advantages of green process, mild conditions and diversified products. These advantages may expand the product chain based on methanol and alleviate the current problem of biomanufacturing, which is competing with people for food. Elucidating the pathways involving methanol oxidation, formaldehyde assimilation and dissimilation in different natural methylotrophs is essential for subsequent genetic engineering modification, and is more conducive to the construction of novel non-natural methylotrophs. This review discusses the current status of research on methanol metabolic pathways in methylotrophs, and presents recent advances and challenges in natural and synthetic methylotrophs and their applications in methanol bioconversion.

Protective effects of Zizyphus oxyphyla on liver and kidney related serum biomarkers in (CCl4) intoxicate rabbits / Efeitos protetores de Zizyphus oxyphyla em biomarcadores de soro relacionados ao fígado e rim em (CCl4) intoxicam rabbtis

The study was aimed to evaluate the therapeutic effects of Zizyphus oxyphyla leaves methanolic (ZOX-LME), on serum liver, kidney and hematology along with other serum parameters in Carbon tetrachloride (CCl4) intoxicated rabbits. Experimental animals were divided into five groups, six rabbits in each. These were: group NC (normal control), group, TC (toxic control) and group ST i.e. silymarine administered group at dose rate (50) mg/kg body weight (BW). Group ET1 and group ET2 treated with (ZOX-LME) at dose 200 mg/kg BW and 400 mg/kg BW. CCl4 administration caused significant (P> 0.05) impairment in serum liver enzymes, blood factors and other serum indices. Treatment with (ZOX-LME) significantly (P<0.05) reduced and normalized the levels of serum alanine transaminase (ALT) aspartate transaminase (AST) and alkaline phosphatase (ALP) and hematological indices. Also significant (P< 0.05) reduction was observed in creatinine, urea, uric acid, blood urea nitrogen (BUN), and albumin and glucose concentrations. The altered levels of lipid profile and serum electrolytes (Ca, Mg, Cl, Na, K, and P) were significantly (P<0.05) change toward normal levels with (ZOX-LME) feeding. In addition (ZOX-LME) ingestion caused significant improvement in GSH, GST and CAT levels, while reducing the TBARS levels, exhibited antioxidant capacity. Also (ZOX-LME) showed increase inhibition against percent scavenging of 2, 2-diphenile-1-picrylehydrazyle (DPPH) free radical. Significant (P<0.05) normalizing effects were observed with high dose 400 mg/kg BW of (ZOX-LME and were equivalent to silymarine administered groups. The histological study of liver supported the hepatoprotective and renal curative activity of (ZOX-LME).

O estudo teve como objetivo avaliar os efeitos terapêuticos das folhas metanólicas de Zizyphus oxyphyla (ZOX-LME) no fígado, rim e hematologia séricos, juntamente com outros parâmetros séricos em coelhos intoxicados com tetracloreto de carbono (CCl4). Os animais experimentais foram divididos em cinco grupos, seis coelhos em cada. Estes foram: grupo NC (controle normal), grupo TC (controle tóxico) e grupo ST, isto é, grupo administrado com silimarina na taxa de dose (50) mg / kg de peso corporal (PC). Grupo ET1 e grupo ET2 tratado com (ZOX-LME) na dose de 200 mg / kg de peso corporal e 400 mg / kg de peso corporal. A administração de CCl4 causou prejuízo significativo (P > 0,05) nas enzimas hepáticas séricas, fatores sanguíneos e outros índices séricos. O tratamento com (ZOX-LME) reduziu significativamente (P < 0,05) e normalizou os níveis de alanina transaminase (ALT), aspartato transaminase (AST) e fosfatase alcalina (ALP) e os índices hematológicos. Também foi observada redução significativa (P < 0,05) nas concentrações de creatinina, ureia, ácido úrico, nitrogênio ureico no sangue (BUN), albumina e glicose. Os níveis alterados de perfil lipídico e eletrólitos séricos (Ca, Mg, Cl, Na, K e P) foram significativamente (P < 0,05) mudando em direção aos níveis normais com a alimentação (ZOX-LME). Além disso, a ingestão de (ZOX-LME) causou melhora significativa nos níveis de GSH, GST e CAT, enquanto reduzia os níveis de TBARS, exibindo capacidade antioxidante. Também (ZOX-LME) mostrou inibição aumentada contra a eliminação percentual do radical livre 2, 2-difenila-1-picrilehidrazila (DPPH). Efeitos de normalização significativos (P < 0,05) foram observados com altas doses de 400 mg / kg de peso corporal de (ZOX-LME) e foram equivalentes aos grupos administrados com silimarina. O estudo histológico do fígado confirmou a atividade hepatoprotetora e curativa renal de (ZOX-LME).

Protective effects of Zizyphus oxyphyla on liver and kidney related serum biomarkers in (CCl4) intoxicate rabbits

Abstract The study was aimed to evaluate the therapeutic effects of Zizyphus oxyphyla leaves methanolic (ZOX-LME), on serum liver, kidney and hematology along with other serum parameters in Carbon tetrachloride (CCl4) intoxicated rabbits. Experimental animals were divided into five groups, six rabbits in each. These were: group NC (normal control), group, TC (toxic control) and group ST i.e. silymarine administered group at dose rate (50) mg/kg body weight (BW). Group ET1 and group ET2 treated with (ZOX-LME) at dose 200 mg/kg BW and 400 mg/kg BW. CCl4 administration caused significant (P> 0.05) impairment in serum liver enzymes, blood factors and other serum indices. Treatment with (ZOX-LME) significantly (P 0.05) reduced and normalized the levels of serum alanine transaminase (ALT) aspartate transaminase (AST) and alkaline phosphatase (ALP) and hematological indices. Also significant (P 0.05) reduction was observed in creatinine, urea, uric acid, blood urea nitrogen (BUN), and albumin and glucose concentrations. The altered levels of lipid profile and serum electrolytes (Ca, Mg, Cl, Na, K, and P) were significantly (P 0.05) change toward normal levels with (ZOX-LME) feeding. In addition (ZOX-LME) ingestion caused significant improvement in GSH, GST and CAT levels, while reducing the TBARS levels, exhibited antioxidant capacity. Also (ZOX-LME) showed increase inhibition against percent scavenging of 2, 2-diphenile-1-picrylehydrazyle (DPPH) free radical. Significant (P 0.05) normalizing effects were observed with high dose 400 mg/kg BW of (ZOX-LME and were equivalent to silymarine administered groups. The histological study of liver supported the hepatoprotective and renal curative activity of (ZOX-LME).

Resumo O estudo teve como objetivo avaliar os efeitos terapêuticos das folhas metanólicas de Zizyphus oxyphyla (ZOX-LME) no fígado, rim e hematologia séricos, juntamente com outros parâmetros séricos em coelhos intoxicados com tetracloreto de carbono (CCl4). Os animais experimentais foram divididos em cinco grupos, seis coelhos em cada. Estes foram: grupo NC (controle normal), grupo TC (controle tóxico) e grupo ST, isto é, grupo administrado com silimarina na taxa de dose (50) mg / kg de peso corporal (PC). Grupo ET1 e grupo ET2 tratado com (ZOX-LME) na dose de 200 mg / kg de peso corporal e 400 mg / kg de peso corporal. A administração de CCl4 causou prejuízo significativo (P > 0,05) nas enzimas hepáticas séricas, fatores sanguíneos e outros índices séricos. O tratamento com (ZOX-LME) reduziu significativamente (P 0,05) e normalizou os níveis de alanina transaminase (ALT), aspartato transaminase (AST) e fosfatase alcalina (ALP) e os índices hematológicos. Também foi observada redução significativa (P 0,05) nas concentrações de creatinina, ureia, ácido úrico, nitrogênio ureico no sangue (BUN), albumina e glicose. Os níveis alterados de perfil lipídico e eletrólitos séricos (Ca, Mg, Cl, Na, K e P) foram significativamente (P 0,05) mudando em direção aos níveis normais com a alimentação (ZOX-LME). Além disso, a ingestão de (ZOX-LME) causou melhora significativa nos níveis de GSH, GST e CAT, enquanto reduzia os níveis de TBARS, exibindo capacidade antioxidante. Também (ZOX-LME) mostrou inibição aumentada contra a eliminação percentual do radical livre 2, 2-difenila-1-picrilehidrazila (DPPH). Efeitos de normalização significativos (P 0,05) foram observados com altas doses de 400 mg / kg de peso corporal de (ZOX-LME) e foram equivalentes aos grupos administrados com silimarina. O estudo histológico do fígado confirmou a atividade hepatoprotetora e curativa renal de (ZOX-LME).

Mechanism of Indole-3-Methanol in Treatment of Obesity Based on Network Pharmacology and in Vitro Experiment / 中国实验方剂学杂志

ObjectiveTo preliminarily predict the targets and signaling pathways of indole-3-methanol in the treatment of obesity based on molecular docking technology and network pharmacology， and then verify the prediction results by the experiment in vitro. MethodThe pharmacological targets of indole-3-methanol were obtained from SwissTargetPrediction and literature review. Obesity-related targets were obtained from Online Mendelian Inheritance in Man （OMIM）， GeneCards， and Comparative Toxicogenomics Database （CTD）. The protein-protein interaction network of the targets of indole-3-methanol and obesity was built by STRING. Cytoscape 3.8.2 was used for target screening. Gene ontology （GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment were performed for the common targets shared by obesity and indole-3-methanol in DAVID 6.8. AutoDock Vina 1.1.2 was employed to perform the molecular docking between indole-3-methanol and disease targets. Finally， the in vitro experiment was carried out to verify the anti-obesity effect of indole-3-methanol. ResultIndole-3-methanol and obesity shared 80 common targets， which included matrix metalloproteinase （MMP）-9， Janus kinase （JAK） 2， etc. KEGG enrichment predicted that indole-3-methanol mainly acted on tumor necrosis factor （TNF）， vascular endothelial growth factor （VEGF）， tyrosine kinase receptor 2 （ErbB2）， and epidermal growth factor receptor （EGFR） signaling pathways in the treatment of obesity. Molecular docking showed that indole-3-methanol had good binding activity with fat mass and obesity-associated protein （FTO）. The results of Western blot， MTT assay， and oil-red O staining showed that indole-3-methanol down-regulated the expression of FTO in 3T3-L1 cells （P<0.05）. ConclusionIndole-3-methanol may treat obesity by down-regulating the expression of FTO protein and further inhibiting adipocyte proliferation. This study provides an experimental basis for deciphering the anti-obesity mechanism of indole-3-methanol.

The preventive effect of exogenous adenosine triphosphate on methanol-induced cardiotoxicity in rats

Abstract Exposure to methanol can cause serious consequences such as permanent visual disturbances and death. The heart tissue is highly vulnerable to ATP deficiency. Our study aimed to investigate whether exogenous ATP administration may alleviate methanol-induced ATP deficiency and subsequent oxidative damage in rat heart tissue. A total of 30 rats were divided into equal five groups; Healthy Group (HG), Methotrexate (MXG), Methanol (MeOH), Methotrexate+Methanol (MXM), and Methotrexate+Methanol+ATP (MMA) groups. We inhibited tetrahydrofolate synthesis by methotrexate to induce methanol toxicity. Methotrexate was administered to MXG, MXM, and MMA group animals for seven days with a catheter directly to the stomach at a 0,3 mg/kg dose per day. At the end of this period, % 20 methanol at a dose of 3 g/kg was administered to MeOH, MMA and MXM group animals. Immediately after methanol application, MMA group animals were injected with ATP at a 4 mg/kg dose intraperitoneally. Blood samples and heart tissues were used for biochemical analysis and histopathological examination. Co-exposure to methanol and methotrexate substantially exacerbated cardiac damage, indicating the potent cardiotoxic effects of methanol. However, the administration of exogenous ATP to MMA group animals brought biochemical oxidative damage parameters and histopathological findings closer to HG.

Simulation of density, viscosity and ultrasonic velocity data of 3-bromoanisole + methanol mixtures at different temperatures

SUMMARY Aim: To represent mathematically the reported physico-chemical properties (PCPs) of binary mixtures of 3-bromoanisol + methanol at various temperatures by using a single model with seven curve-fit parameters. Results: Besides the correlation models, the applicability of training the proposed model using a minimum number of experimental data and prediction of the rest of data points with acceptable prediction error is also shown.

Objetivo: representar matemáticamente las propiedades fisicoquímicas (PCP) de mezclas binarias de 3-bromoanisol + metanol a varias temperaturas, utilizando un modelo único con siete parámetros de ajuste de curva. Resultados: además de los modelos de correlación, también se muestra la aplicabilidad del entrenamiento del modelo propuesto utilizando un número mínimo de datos experimentales y la predicción del resto de puntos de datos con un error de predicción aceptable.

Objetivo: representar matematicamente as propriedades físico-químicas reportadas (PCPs) de misturas binárias de 3-bromoanisol + metanol em várias temperaturas usando um único modelo com sete parâmetros de ajuste de curva. Resultados: além dos modelos de correlação, a aplicabilidade do treinamento do modelo proposto usando um número mínimo de dados experimentais e previsão do restante dos pontos de dados com erro de previsão aceitável também é mostrada.

Anticarcinogenic activity of methanol extract of Melastoma malabathricum leaves is attributed to the presence of phenolics compounds and the activation of endogenous antioxidant system / Actividad anticancerígena del extracto metanólico de hojas de Melastoma malabathricum atribuida a la presencia de compuestos fenólicos y a la activación del sistema antioxidante endógeno

Melastoma malabathricum (M. malabathricum) extracts have been reported to exert various pharmacological activities including antioxidants, anti-inflammatory and antiproliferative activities. The objective of the present study was to determine the anticarcinogenic activity of its methanol extract (MEMM) against the azoxymethane (AOM)-induced early colon carcinogenesis in rats. Rats were randomly assigned to five groups (n=6) namely normal control, negative control, and treatment (50, 250 or 500 mg/kg of MEMM) groups. Colon tissues were harvested for histopathological analysis and endogenous antioxidant system determination. MEMM was also subjected to HPLC analysis. Findings showed that MEMM significantly (p<0.05) reversed the AOM-induced carcinogenicity by: i) reducing the formation of aberrant crypt foci (ACF) in colon tissues, and; ii) enhancing the endogenous antioxidant activity (catalase, superoxide dismutase and glutathione peroxidase). Moreover, various phenolics has been identified in MEMM. In conclusion, MEMM exerts the in vivo anticarcinogenic activity via the activation of endogenous antioxidant system and synergistic action of phenolics.

Se ha informado que los extractos de Melastoma malabathricum (M. malabathricum) ejercen diversas actividades farmacológicas, incluidas actividades antioxidantes, antiinflamatorias y antiproliferativas. El objetivo del presente estudio fue determinar la actividad anticancerígena de su extracto de metanol (MEMM) contra la carcinogénesis de colon temprana inducida por azoximetano (AOM) en ratas. Las ratas se asignaron al azar a cinco grupos (n=6), a saber, los grupos de control normal, control negativo y tratamiento (50, 250 o 500 mg/kg de MEMM). Tejidos de colon fueron recolectados para análisis histopatológico y determinación del sistema antioxidante endógeno. MEMM también se sometió a análisis de HPLC. Los hallazgos mostraron que MEMM invirtió significativamente (p<0.05) la carcinogenicidad inducida por AOM al: i) reducir la formación de focos de criptas aberrantes (ACF) en los tejidos del colon, y; ii) potenciar la actividad antioxidante endógena (catalasa, superóxido dismutasa y glutatión peroxidasa). Además, se han identificado varios fenólicos en MEMM. En conclusión, MEMM ejerce la actividad anticancerígena in vivo mediante la activación del sistema antioxidante endógeno y la acción sinérgica de los fenólicos.

Clinical features and follow-up outcomes of optic nerve injury induced by acute methanol poisoning / 中华劳动卫生职业病杂志

Acute methanol poisoning harms the optic nerve and central nervous system, can cause irreversible damage, even coma or death in severe cases. This article reported four cases of methanol poisoning. 3 patients mistakenly ingested industrial alcohol containing methanol, the most serious patient suffered from coma, vision loss and other symptoms, the blood methanol concentration was 869.3 μg/ml. Another patient was poisoning caused by inhalation of methanol, with symptoms such as total blindness in the right eye and decreased visual acuity in the left eye. After active supportive treatment, 2 patients had partial recovery of visual acuity, and 2 patients had no sequelae. This article discussed the clinical features, treatment and prognosis of optic nerve damage caused by methanol poisoning, in order to raise awareness of this disease.

Research status of occupational methanol poisoning based on literature bibliometrics / 中国职业医学

@#Objective To analyze the research status and hotspot of occupational methanol poisoning at home and abroad. Methods ， The China National Knowledge Resource Database Wanfang Data Knowledge Service Platform and Web of Science were used as the data sources. The relevant literatures on occupational methanol poisoning published in domestic and foreign ， Results journals up to June 30 2021 were searched. The bibliometrics was used to analyzed the literatures. A total of 255 literatures were included in analysis. There were 187 Chinese articles and 68 English articles. Most of Chinese articles were ， ， published from 2001 to 2005 with an average of 26.7 literatures per five years until June 2021. Among them 72 literatures （ ）， ， were published in core journals 38.5% and 176 authors from 27 provinces autonomous regions and municipality directly ， under the central government published relevant literatures. The research contents mainly focused on the classification ， ， poisoning mode clinical manifestations visual impairment and poisoning prevention and treatment of occupational methanol - ， poisoning. Most of the English literatures were published in 2016 2020 with an average of 4.9 articles per five years until June ， （ ）， 2021. Among them 36 were published in SCI journals 52.9% and 57 authors from 11 countries published relevant ， ， ， literatures. The research contents mainly focused on the clinical diagnosis drug treatment intoxication mechanism visual Conclusion sequelae and brain injury of occupational methanol poisoning. The research on occupational methanol poisoning ， ， ， mainly focuses on clinical diagnosis clinical manifestations treatment and prognosis and pathogenesis. The focus of relevant research at home and abroad is different.

Composition, Antioxidant and Anti-inflammatory activities of Hexane and Methanol extracts of Acmella uliginosa from Terai region of Uttarakhand

Abstract Acmella uliginosa, an edible herb belonging to Asteraceae family, was collected from the Terai region of Uttarakhand, India. Methanol and hexane extracts of the whole plant were prepared using soxhlet apparatus. The GC-MS analysis of plant extracts identifies 22 and 35 major compounds of methanol and hexane extracts which comprises of 74.21% and 73.20% of the total composition of extracts, respectively. The major compound in hexane was 2, 4-heptadienal (7.99%) whereas trans, trans-9, 12-octadecadienoic acid propyl ester (16.96%) was major compound in methanol extract. The extracts were evaluated for antioxidant and anti-inflammatory properties. Methanol extract showed higher free radical scavenging and reducing power activities with IC50 value 153.82±1.69 µg/mL and RP50 value of 152.28±0.41 µg/mL, respectively. The metal chelating activity was higher in hexane extract as compared to methanol extract i.e., 62.08±0.25 µg/mL. The anti-inflammatory activity assessed by its ability to inhibit denaturation was higher in methanol having IB50 value 87.33±0.15 µg/mL. The total phenolic content (TPC), total flavonoid content (TFC) and ortho-dihydric phenol content (ODP) of methanol and hexane extracts were also evaluated. TPC, TFC and ODP was higher in methanol extract having value of 122.23±0.22, 35.01±0.29 and 8±0.86 mg/mL, respectively. Acmella uliginosa, might be considered as a natural source for antioxidant and anti-inflammatory properties

A proline derivative-enriched methanol fraction from Sideroxylon obtusifolium leaves (MFSOL) stimulates human keratinocyte cells and exerts a healing effect in a burn wound model

It was previously demonstrated that the methanol fraction of Sideroxylon obtusifolium (MFSOL) promoted anti-inflammatory and healing activity in excisional wounds. Thus, the present work investigated the healing effects of MFSOL on human keratinocyte cells (HaCaT) and experimental burn model injuries. HaCaT cells were used to study MFSOL's effect on cell migration and proliferation rates. Female Swiss mice were subjected to a second-degree superficial burn protocol and divided into four treatment groups: Vehicle, 1.0% silver sulfadiazine, and 0.5 or 1.0% MFSOL Cream (CrMFSOL). Samples were collected to quantify the inflammatory mediators, and histological analyses were performed after 3, 7, and 14 days. The results showed that MFSOL (50 μg/mL) stimulated HaCaT cells by increasing proliferation and migration rates. Moreover, 0.5% CrMFSOL attenuated myeloperoxidase (MPO) activity and also stimulated the release of interleukin (IL)-1β and IL-10 after 3 days of treatment. CrMFSOL (0.5%) also enhanced wound contraction, promoted improvement of tissue remodeling, and increased collagen production after 7 days and VEGF release after 14 days. Therefore, MFSOL stimulated human keratinocyte (HaCaT) cells and improved wound healing via modulation of inflammatory mediators of burn injuries.

Advances in metabolic engineering of methylotrophic yeasts / 生物工程学报

Methylotrophic yeasts are considered as promising cell factories for bio-manufacturing due to their several advantages such as tolerance to low pH and high temperature. In particular, their methanol utilization ability may help to establish a methanol biotransformation process, which will expand the substrate resource for bio-refinery and the product portfolio from methanol. This review summarize current progress on engineering methylotrophic yeasts for production of proteins and chemicals, and compare the strengths and weaknesses with the model yeast Saccharomyces cerevisiae. The challenges and possible solutions in metabolic engineering of methylotrophic yeasts are also discussed. With the developing efficient genetic tools and systems biology, the methylotrophic yeasts should play more important roles in future green bio-manufacturing.

Methanol dehydrogenase, a key enzyme of one-carbon metabolism: a review / 生物工程学报

One-carbon compounds such as methanol and methane are cheap and readily available feedstocks for biomanufacturing. Oxidation of methanol to formaldehyde catalyzed by methanol dehydrogenase (MDH) is a key step of microbial one-carbon metabolism. A variety of MDHs that depend on different co-factors and possess different enzymatic properties have been discovered from native methylotrophs. Nicotinamide adenine dinucleotide (NAD)-dependent MDHs are widely used in constructing synthetic methylotrophs, whereas this type of MDH usually suffers from low methanol oxidation activity and low affinity to methanol. Consequently, methanol oxidation is considered as a rate-limiting step of methanol metabolism in synthetic methylotrophs. To accelerate methanol oxidation, thereby improving the methanol utilization efficiency of synthetic methylotrophs, massive researches have focused on discovery and engineering of MDHs. In this review, we summarize the ongoing efforts to discover, characterize, and engineer various types of MDHs as well as the applications of MDHs in synthetic methylotrophs. Directed evolution of MDH and construction of multi-enzyme complexes are described in detail. In the future prospective part, we discuss the potential strategies of growth-coupled protein evolution and rational protein design for acquisition of superior MDHs.

Determination of formic acid in urine by automatic headspace-gas chromatography-mass spectrometry / 中国职业医学

OBJECTIVE: To establish a method for the determination of formic acid in urine by automatic headspace-gas chromatography-mass spectrometry. METHODS: The urine sample was added with 3 mL 15.00%(V/V) sulfuric acid ethanol and heated in an automatic headspace sampler. The formic acid and ethanol underwent an esterification reaction to produce ethyl formate which was separated by gas chromatographic column and detected by mass spectrometer. The quantification was based on external standard method. RESULTS: The linear range of the method was 2.93-97.60 mg/L, with the regression equation correlation coefficient of 0.999 5. The detection limit was 0.65 mg/L and the minimum quantitative limit was 2.17 mg/L, with the recoveries of 95.61%-106.47%. The within-run relative standard deviation(RSD) ranged from 2.52% to 8.05% and the between-run RSD ranged from 6.58% to 8.42%. CONCLUSION: The method has simple pretreatment, good specificity, high precision and has little interference. It is suitable for large scale rapid determination of formic acid in urine in occupational contact population, patients with acute methanol poisoning and general population.

Release of formaldehyde during the biofiltration of methanol vapors in a peat biofilter inoculated with Pichia pastoris GS115

BACKGROUND: Methanol can be effectively removed from air by biofiltration (Shareefdeen et al., 1993; Babbitt et al., 2009 [1,2]). However, formaldehyde is one of the first metabolic intermediates in the consumption of methanol in methylotrophic microorganisms (Negruta et al., 2010 [3]), and it can be released out of the cell constituting a secondary emission. RESULTS: The total removal of methanol was achieved up to input loads of 263 g m−3 h−1 and the maximum elimination capacity of the system was obtained at an empty bed residence times of 90 s and reached 330 g m−3 h−1 at an input methanol load of 414 g m−3 h−1 and 80% of removal efficiency. Formaldehyde was detected inside the biofilter when the input methanol load was above 212 g m−3 h−1 . Biomass in the filter bed was able to degrade the formaldehyde generated, but with the increase of the methanol input load, the unconsumed formaldehyde was released outside the biofilter. The maximum concentration registered at the output of the system was 3.98 g m−3 when the methanol load was 672 g m−3 h−1 in an empty bed residence times of 60 s. CONCLUSIONS: Formaldehyde is produced inside a biofilter when methanol is treated in a biofiltration system inoculated with Pichia pastoris. Biomass present in the reactor is capable of degrading the formaldehyde generated as the concentration of methanol decreases. However, high methanol loads can lead to the generation and release of formaldehyde into the environment.

Mikania cordata leaves extract promotes activity against pathogenic bacteria and anticancer activity in EAC cell-bearing swiss albino mice

This study was aimed to screen the activity of the methanolic extract of Mikania cordata leaves (MLME) againstpathogenic bacteria and Ehrlich ascites carcinoma (EAC)-induced cancer in mice. Antibacterial activity was testedagainst some Gram-positive (Bacillus subtilis IFO 3026 and Sarcina lutea IFO 3232) and Gram-negative (Klebsiellapneumoniae ATTC 10031, Proteus vulgaris MTTC 321, Pseudomonas denitrificans KACC 32026, and Xanthomonascampestris IAM 1671) bacteria by disk diffusion and liquid microdilution assay. The anticancer activity wasassessed by EAC cell death, apoptosis, hematological parameters determination, and 3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide test. The MLME exhibited prominent antibacterial activity against the test strains.The minimum inhibitory concentrations were ranged from 1.25 to 20 mg/ml for the bacterial strains that were foundampicillin resistant. The MLME exhibited remarkable anticancer activity on EAC in a dose-dependent manner. Oralintake of MLME at the dosage of 400 mg/kg body weight (b.w) exhibited the highest EAC cell death with remarkableapoptotic features including chromatin condensation, nuclear fragmentation, and accumulation of apoptotic bodies.The MLME-treated EAC-bearing mice showed dose-dependently restored altered hematological parameters towardthe normal level. The IC50 value was 6.6 ± 1.91 µg/ml. These findings suggest that the M. cordata leaves have strongantibacterial and anticancer properties.

Investigation of Paidu Qingzhi Tablets Based on UPLC-Q-TOF-MS and Network Pharmacology / 中国实验方剂学杂志

Objective::To identify the active constituents of Paidu Qingzhi tablets by UPLC-Q-TOF-MS technique, and to reveal its potential targets and molecular mechanisms by network pharmacology. Method::Chromatography separation was achieved on an ACQUITY UPLC HSS T3 column (2.1 mm×100 mm, 1.8 μm) with mobile phase consisted of 0.1% formic acid aqueous solution and acetonitrile for gradient elution (0-17 min, 95%-5%A; 17-17.01 min, 5%-95%A; 17.01-20 min, 95%A), the flow rate was 0.3 mL·min-1, the column temperature was 40 ℃. Data acquisition was carried out in electrospray ionization (ESI) under the negative ion mode, the scanning range was 50-1 200.Ingredients in Paidu Qingzhi tablets were identified according to reference substance, relative molecular weight, mass spectrometric cleavage rule and literature information. Multiple databases were used to retrieve the targets of these identified ingredients and related diseases treated by the tablets, and metabolic pathways. A visual network of " herbs-compounds-targets-pathways-diseases" was constructed by Cytoscape 3.7.1. Result::A total of 33 active compounds in methanol extract of Paidu Qingzhi tablets were identified by UPLC-Q-TOF-MS, including 27 compounds from Rhei Radix et Rhizoma, 4 compounds from Panacis Quinquefolii Radix, 2 compounds from Ophiopogonis Radix. Totally 18 direct targets and 58 indirect targets corresponding to 31 ingredients were obtained, 7 metabolic pathways including steroid hormone biosynthesis pathway, arachidonic acid metabolic pathway, insulin signaling pathway were strongly correlated with the treatment of hyperlipidemia, acne and simple obesity by Paidu Qingzhi tablets. Conclusion::Ingredients of Paidu Qingzhi tablets are revealed by UPLC-Q-TOF-MS, based on these identified ingredients, targets and related metabolic pathways are visualized by network pharmacology. The current research can provide theoretical basis for quality control and clinical application of Paidu Qingzhi tablets.

Comparative Analysis of Chemical Composition in Methanol and Petroleum Ether Fractions from Curcuma longa of Different Habitats / 中国药房

OBJECTIVE：To compare the chemical compo sition difference in methanol and petroleum ether fraction from Curcuma longa of different habitats. METHODS ：The ultrasonic method was used to extract C. longa from 7 defferent producingareas（S1-S7），and methanol and petroleum ether fraction were obtained and calculated yield. The curcumin compounds in methanol fraction were determined by LC-MS ；The chemical components in petroleum ether fraction were analyzed by GC-MS ， and the relative percentage content was determined by peak area normalization method after determining its structure by comparing NIST 2005 standard mass spectra and Wiley 275 standard mass spectra. SPSS 25.0 software was used for principle component analysis（PCA）and cluster analysis of relative percentage content of common components in petroleum ether fraction from C. longa of different habitats. At the same time ，the influence of latitude of the habitats on the content of total tumerone （by tumerone and ar-tumerone ）was analyzed. RESULTS ：The yield of methanol fraction were 1.35％-8.90％ from C. longa of 7 habitats；the yield of petroleum ether fraction were 0.81％-4.90％，which were the highest in C. longa from Longyan of Fujian Province. There was no significant difference in the relative content of curcumin compounds（reference peak area ）from S 1，S3-S7，which was in descending order as follows as curcumin ＞desmethoxycurcumin＞bisdemethoxycurcumin. There was slightly different in curcumin compounds of C. longa from S 2，mainly manifesting as the content of bisdemethoxycurcumin was higher than that from other producing areas. Totally 48 chemical compositions were identified from petroleum ether fraction in C. longa from different habitats ， mainly being sesquiterpenoids and monoterpenoids. 23，10，15，18，11，14，15 chemical compositions were identified from S1-S7，accounting for 94.49％，96.09％，95.66％，98.98％，99.24％，89.05％ and 97.27％. There were 4 common compositions in C. longa from different habitats ，which were tumerone （17.90％-43.07％），ar-tumerone（6.97％-33.66％），（6R，7R）-bisabolone （1.60％-4.28％），curlone（6.80％-20.63％）. PCA analysis showed that accumulative contribution rate of former 6 principle components was 100％. Cluster analysis showed that S1，S2， S6 was clustered into a category ，respecrively；and others intoa category. Total content of total tumerone decreased first and then increased as the increase of latitude ，which was the highest in Mianyang of Sichuan province （64.28％）and the lowest in Zhangzhou of Fujian province （26.92％）. CONCLUSIONS ： There are difference in composition and content of methanol and petroleum ether fractions in C. longa from different habitats.