Advances in gas fumigation technologies for postharvest fruit preservation.

This work summarizes the application of gas fumigation technology in postharvest fruit quality management and related biochemical mechanisms in recent years. Gas fumigants mainly include SO2, ClO2, ozone, NO, CO, 1-MCP, essential oils, H2S and ethanol. This work indicated that gas fumigation preservatives can effectively improve postharvest fruit quality, which is mainly manifested in delaying senescence, inhibiting browning, controlling disease and alleviating chilling injury. Gas preservatives are mainly involved in postharvest fruit quality control in the roles of antifungal agent, anti-browning agent, redox agent, ethylene inhibitors, elicitor and pesticide remover. Different gas preservatives have different roles, but most of them have multiple roles at the same time in postharvest fruit quality management. In addition, the role of some gas preservatives with direct antifungal activity in the control of postharvest fruit diseases can also activate defense systems to improve fruit resistance. It should be noted that some gas fumigation treatments with slow-release effects have been developed recently, which may allow gas fumigation gases to perform better. Moreover, some gas fumigants can cause irrational side effects on the fruit and some combined treatments need to be found to counteract such side effects.

An update of aurones: food resource, health benefit, biosynthesis and application.

Aurones are a subclass of active flavonoids characterized with a scaffold of 2-benzylidene-3(2H)-benzofuranone. This type of chemicals are widely distributed in fruit, vegetable and flower, and contribute to human health. In this review, we summarize the natural aurones isolated from dietary plants. Their positive effects on immunomodulation, antioxidation, cancer prevention as well as maintaining the health status of cardiovascular, nervous system and liver organs are highlighted. The biosynthesis strategies of plant-derived aurones are elaborated to provide solutions for their limited natural abundance. The potential application of natural aurones in food coloration are also discussed. This paper combines the up-to-date information and gives a full image of dietary aurones.

Systematic review and meta-analysis of the efficacy of olprinone and MEFV gene in treating heart failure.

Cardiovascular failure is the main cause of death in industrialized societies. The results of recent studies have shown that some mutations in the MEFV gene are common in heart failure patients. For this reason, the study of mutations and genetic factors has been of great help in the treatment of this disease, but despite this, due to the heterogeneity of clinical symptoms, multiple pathophysiological processes, and environmental genetic factors, the complete understanding of the genetic causes of this disease is very complicated. As the new generation of phosphodiesterase (PDE) III inhibitor, olprinone, the inhibition of human heart PDE III by olprinone is highly selective. It is suitable for the treatment of acute heart failure (HF) and acute cardiac insufficiency after cardiac surgery. In this study Olprinone, milrinone, PDE inhibitors, cardiac failure, and HF were selected as the search terms to retrieve articles published between January 1999 and March 2022. RevMan5.3 and Stata were employed to analyze and evaluate the risk bias of the included articles. Besides, the Q test and heterogeneity were utilized to evaluate the heterogeneity between articles. The results of this research showed No heterogeneity was found between each research group. The sensitivity (Sen) and specificity (Spe) of the two methods were compared. Olprinone showed more significant therapeutic effects than other PDE inhibitors. Besides, the therapeutic effect on the patients with HF in the two groups was obvious. The incidence of postoperative adverse reactions among the patients without relieving HF was low. The influences on urine flow of the two group's demonstrated heterogeneity, and its effect revealed no statistical meaning. The meta-analysis confirmed that the Spe and Sen of olprinone treatment were higher than those of other PDE inhibitors. In terms of hemodynamics, there was little difference between various treatment methods.

Regulation of Embden-Meyerhof-Parnas (EMP) Pathway and Tricarboxylic Acid (TCA) Cycle Concerning Aberrant Chilling Injury Behavior in Postharvest Papaya (Carica papaya L.).

Postharvest abnormal chilling injury (CI) behavior in papaya (Carica papaya L.) fruit is a rare phenomenon that may be associated with respiratory metabolism. This study thus aimed to investigate the impacts of storage temperatures (1 and 6 °C) on the respiratory metabolism of postharvest papaya and its impact on CI development. Results demonstrated that 1 °C storage reduced the activities of hexokinase (HK), phosphofructokinase (PFK), pyruvate kinase (PK), citrate synthase (CS), and α-ketoglutarate dehydrogenase (α-KGDH) and regulated the expression of corresponding enzymes in the Embden-Meyerhof-Parnas (EMP) pathway and tricarboxylic acid (TCA) cycle compared with 6 °C storage, resulting in a lower respiration rate of the EMP-TCA pathway and mitigating the development of CI. Meanwhile, lower contents of nicotinamide adenine dinucleotide (hydrogen) (NAD(H)) were observed in papaya fruit stored at 1 °C. Notably, papaya fruit stored at 1 °C maintained higher activity and transcriptional levels of SDH and IDH during the whole storage period. These findings suggest that 1 °C storage reduced the respiration rate of the EMP-TCA pathway by reducing the expression level and activity of related enzymes, which is conducive to the reduction of respiration substrate consumption and finally alleviating the occurrence of CI.

Pathway Analysis and Metabolites Identification by Metabolomics of Etiolation Substrate from Fresh-Cut Chinese Water Chestnut (Eleocharis tuberosa).

Fresh-cut Chinese water chestnuts (CWC) turn yellow after being peeled, reducing their shelf life and commercial value. Metabolomics, the systematic study of the full complement of small molecular metabolites, was useful for clarifying the mechanism of fresh-cut CWC etiolation and developing methods to inhibit yellowing. In this study, metabolic alterations associated with etiolation at different growth stages (0 day, 2 days, 3 days, 4 days, 5 days) from fresh-cut CWC were investigated using LC-MS and analyzed by pattern recognition methods (principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), and orthogonal projection to latent structures-discriminant analysis (OPLS-DA)). The metabolic pathways of the etiolation molecules were elucidated. The main metabolic pathway appears to be the conversion of phenylalanine to p-coumaroyl-CoA, followed by conversion to naringenin chalcone, to naringenin, and naringenin then following different pathways. Firstly, it can transform into apigenin and its derivatives; secondly, it can produce eriodictyol and its derivatives; and thirdly it can produce dihydrokaempferol, quercetin, and myricetin. The eriodictyol can be further transformed to luteolin, cyanidin, dihydroquercetin, dihydrotricetin, and others. This is the first reported use of metabolomics to study the metabolic pathways of the etiolation of fresh-cut CWC.

Tert-Butylhydroquinone retards longan fruit deterioration by regulating membrane lipid and energy metabolisms.

Longan fruit deteriorates rapidly after harvest, which limits its storability. This study aimed to investigate the effect of tert-butylhydroquinone (TBHQ) on quality maintenance, membrane lipid metabolism, and energy status of longan fruit during 25 °C storage. Compared with control fruit, TBHQ treatment maintained better marketable fruit rate and suppressed activities of phospholipase D (PLD), lipase, and lipoxygenase (LOX), and downregulated expressions of DlPLD, DlLOX, and Dllipase. TBHQ also increased the ratio of unsaturated fatty acids to saturated fatty acids (U/S) and the index of unsaturated fatty acids (IUFA). In addition, higher levels of ATP, ADP, energy charge, NADP+/ NADPH as well as higher activities of H+-ATPase, Ca2+-ATPase and NADK were also observed in TBHQ-treated fruit. These results suggested that TBHQ may maintain postharvest quality of longan fruit by regulating membrane lipid and energy metabolisms.

Investigation on epidermal structure and water migration of postharvest passion fruit during storage.

Passion fruit is a tropical fruit that has plenty of fruit fragrance. During storage, passion fruit quickly loses water, resulting in its poor quality. Researching the mechanism of water loss contributes to prolonging the storage time. In this study, passion fruit was stored at 7 or 25°C to analyze the relationship between epidermal structure and water migration. The epidermal wax and structure of passion fruit began to show signs of destruction from the middle stage (day 8) during storage. The mobility of free water was decreased at 7°C and increased at 25°C in passion fruit from the middle stage of storage (day 8). The migration rate of free water in passion fruit stored at 7°C was lower than that at 25°C. The mobility of immobile water was weaker in the late storage period but that of bound water changed barely. These results showed that the migration of free, immobile, and bound water had a connection with the epidermal structure. Incomplete epidermal structure promoted water loss in passion fruit, with the most pronounced loss of free water. PRACTICAL APPLICATION: Maintaining the epidermal structure of passion fruit well can decrease the water loss ratio. Passion fruit stored at low temperatures could better sustain the integrity of epidermal wax and structure; it was able to change the water migration rate in the epidermis of passion fruit, which was conducive to maintaining the water content.

Eco-friendly simultaneous extraction of pectins and phenolics from passion fruit (Passiflora edulis Sims) peel: Process optimization, physicochemical properties, and antioxidant activity.

The objective of this study was to simultaneously extract passion fruit (Passiflora edulis) peel pectins and phenolics using deep eutectic solvents, to evaluate their physicochemical properties and antioxidant activity. By taking L-proline: citric acid (Pro-CA) as the optimal solvent, the effect of extraction parameters on the yields of extracted passion fruit peel pectins (PFPP) and total phenolic content (TPC) was explored by response surfaces methodology (RSM). A maximum pectin yield (22.63%) and the highest TPC (9.68 mg GAE/g DW) were attained under 90 °C, extraction solvent pH = 2, extraction time of 120 min and L/S ratio of 20 mL/g. In addition, Pro-CA-extracted pectins (Pro-CA-PFPP) and HCl-extracted pectins (HCl-PFPP) were subjected to high performance gel permeation chromatography (HPGPC), Fourier transform infrared spectroscopy (FT-IR), thermogram analysis (TG/DTG) and rheological measurements. Results verified that the Mw and thermal stability of Pro-CA-PFPP were higher than those of HCl-PFPP. The PFPP solutions featured a non-Newtonian behavior, and compared with commercially pectin solution, PFPP solution exhibited a stronger antioxidant activity. Additionally, passion fruit peel extract (PFPE) exhibited stronger antioxidant effects than PFPP. The results of ultra-performance liquid chromatography hybrid triple quadrupole-linear ion trap mass spectrometry (UPLC-Qtrap-MS) and high performance liquid chromatography (HPLC) analysis showed that (-)-epigallocatechin, gallic acid, epicatechin, kaempferol-3-O-rutin and myricetin were the main phenolic compounds in PFPE and PFPP. Our results suggest that Pro-CA can be considered as an eco-friendly solvent for high-efficient extraction of high-value compounds from agricultural by-products.

Stability and bioactivity evaluation of black pepper essential oil nanoemulsion.

Black pepper essential oil has the same disadvantages as other plant essential oils, such as volatilization, high sensitivity to light and heat and poor water solubility, which leads to great limitations in application. This study improved the stability and antibacterial properties of black pepper essential oil (BPEO) based on a nano-emulsification process. Tween 80 was selected as the emulsifier to prepare the BPEO nanoemulsion. Gas chromatograph - mass spectrometer (GC-MS) was used to analyze the composition of BPEO, of which d-limonene was the main component (37.41%). After emulsification, black pepper nanoemulsion was obtained (droplet size was 11.8 nm). The water solubility and stability of the emulsions at 25 °C were also improved with decreasing particle size. Antimicrobial properties of plant pathogens (Colletotrichum gloeosporioides, Botryodiplodia theobromae) and foodborne pathogens (Staphylococcus aureus, Escherichia coli) were evaluated by disk diffusion and other techniques for determining minimum inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). With 12.5 mg mL-1 MIC and 25 mg mL-1 MBC, BPEO inhibited the growth of two tested plant pathogens and two foodborne pathogens. Essential oils (EO) were encapsulated in a nanoemulsion system to enhance the bacteriostatic effect of essential oils and reduce MIC and MBC concentrations. After emulsification, the biological activity (antimicrobial and antioxidant) of the BPEO nanoemulsion was considerably improved, nano-emulsification had certain significance for the study of EOs.

Ultrasonic-assisted binding of canistel (Lucuma nervosa A.DC) seed starch with quercetin.

In order to provide a reference for improving the physicochemical properties of starch, the study of starch polyphenol complex interaction has aroused considerable interest. As a common method of starch modification, ultrasound can make starch granules have voids and cracks, and make starch and polyphenols combine more closely. In this research, canistel seed starch was modified by ultrasonic treatment alone or combined with quercetin. The molecular structure, particle characteristics and properties of starch were evaluated. With the increase of ultrasonic temperature, the particle size of the dextrinized starch granules increased, but the addition of quercetin could protect the destruction of starch granule size by ultrasonic; X-ray diffraction and infrared spectra indicated that quercetin was bound to the surface of canistel seed starch through hydrogen bonding, and the complex and the original starch had the same crystal structure and increased crystallinity; by molecular simulation, quercetin bound inside the starch molecular helix preserved the crystalline helical configuration of starch to some extent and inhibited the complete unhelicalization of starch molecules. Meanwhile, hydrogen bonding was the main driving force for the binding of starch molecules to quercetin, and van der Waals interactions also promoted the binding of both. In the physicochemical properties, as the temperature increased after the combination of ultrasonic modified starch combined with quercetin, the solubility, swelling force and apparent viscosity of the compound increased significantly, and it has higher stability and shear resistance.

Abnormal chilling injury of postharvest papaya is associated with the antioxidant response.

Generally, the lower the temperature and/or the longer the duration of low temperature, the more serious chilling injury (CI) symptom appears in fruit. However, our previous study showed that the higher storage temperature (6°C) resulted in a more serious CI in papaya fruit compared to that stored at 1°C, which could be viewed as an abnormal CI behavior. This study investigated the antioxidant responses that existed in abnormal CI behavior of papaya fruit. Compared to 6°C, antioxidant enzyme activities of papaya fruit which was stored at 1°C were maintained at a higher level while the circulatory metabolism of the ascorbate-glutathione cycle (AsA-GSH) was more vigorous in papaya fruit, as indicated by higher superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX), dehydroascorbate reductase (DHAR), and monodehydroascorbate reductase (MDHAR) activities and higher AsA and GSH levels, which could reduce the superoxide anion (·O2 - ) production rate and the hydrogen peroxide (H2 O2 ) content. Suppressed reactive oxygen species (ROS) generation in papaya fruit at 1°C resulted in reduced membrane permeability and malondialdehyde (MDA) accumulation when compared to that at 6°C, thus the development of CI was restricted during storage at 1°C. This study deepened the understanding of differential antioxidant responses during cold storage at 1°C and 6°C in papaya fruit and provided a theoretical basis for further study on the mechanism of the abnormal CI behavior in papaya fruit. PRACTICAL APPLICATIONS: Low-temperature storage is one of the most effective methods to preserve fruit and vegetable products. While, inappropriate low temperature could induce CI, and the damage caused by CI is often more serious than estimated. Therefore, it is necessary to study the physiological and biochemical characteristics of different postharvest fruits and vegetables to prolong storage period, improve storage quality and reduce the loss of products. This study analyzed the antioxidant reaction in abnormal CI behavior of papaya, which could contribute to the further study on the mechanism of CI in papaya fruit and provide theoretical basis for the development of preservation technology of papaya fruit.

The Diuretic Effects of Coconut Water by Suppressing Aquaporin and Renin-Angiotensin-Aldosterone System in Saline-Loaded Rats.

The acute and prolonged diuretic effects of coconut water (CW) and the underlying mechanism were investigated with a saline-loaded rat model. In an acute diuretic experiment, CW could significantly increase urine excretion. In addition, the treatment of CW significantly increased urinary sodium and chloride ions, thereby considerably increasing the excretion of NaCl. However, the calcium concentration and pH value were not affected. In the prolonged diuretic experiment, CW dramatically increased the urine output and urine electrolyte concentrations (Na+, K+, and Cl-). Furthermore, CW could suppress the activation of renin-angiotensin-aldosterone system by decreasing serum antidiuretic hormone, angiotensin II, and aldosterone levels, and significantly increasing the serum atriopeptin level. CW treatment significantly reduced the mRNA expressions and protein levels of aquaporin 1 (AQP1), AQP2, and AQP 3. This report provided basic data for explaining the natural tropical beverage of CW as an alternative diuretic agent.

Attenuation of Postharvest Browning in Rambutan Fruit by Melatonin Is Associated With Inhibition of Phenolics Oxidation and Reinforcement of Antioxidative Process.

Rambutan is a famous tropical fruit with a unique flavor and considerable economic value. However, the high vulnerability to postharvest browning leads to a short shelf life of rambutan fruit. Melatonin (MT) is an excellent bioactive molecule that possesses the potential to improve the storability of the harvested crops. In this study, the physiological mechanism of exogenous MT in affecting pericarp browning and senescence of postharvest rambutan fruit was investigated. Experimental results showed that the application of MT at 0.125 mmol L-1 appreciably retarded the advancement of pericarp browning and color parameters (L*, a*, and b*). MT treatment inhibited the increase in membrane relative electrolytes leakage (REL) while lowering the accumulation of reactive oxygen species (ROS) (■O2 - and H2O2) and malonaldehyde (MDA). Reduced phenolics oxidation, as indicated by higher contents of total phenolics, flavonoids, and anthocyanins along with fewer activities of peroxidase (POD) and polyphenol oxidase (PPO), was detected in MT fruit compared with control fruit. MT treatment maintained the cellular redox state by inducing antioxidant enzyme activity and reinforcing the ascorbate-glutathione (AsA-GSH) cycle. Furthermore, the ultrastructural observation revealed that the spoilage of cellular and subcellular structures was milder in MT fruit than that in control fruit. The results suggest that MT could ameliorate the browning and senescence of rambutan fruit by inhibiting phenolic oxidation and enhancing the antioxidative process.

Abnormal behavior of chilling injury in postharvest papaya fruit is associated with sugar metabolism.

In the most chilling-sensitive fruits and vegetables, usually, the lower the storage temperature, the more serious the symptoms of chilling injury (CI). As one of the special cases, papaya fruits at 1℃ show slighter CI symptoms than those at higher storage temperature. Such abnormal CI phenomenon has not received enough attention and its mechanism is not clear. The present study investigated the difference of CI severity and sugar metabolism in papaya fruits when stored between 1℃ and 6℃. The results showed that CI index in papaya fruits preserved at 1°C was markedly lower than that in fruit at 6°C, which was accompanied by higher content of glucose, fructose, and sucrose. In addition, compared to 6°C, 1°C promoted higher activities of sucrose synthase, sucrose-phosphate synthase, and neutral invertase, but lowered acid invertase activity. RT-qPCR analysis showed that 1°C upregulated the CpSPS expression and downregulated the CpAI expression when compared to 6°C. The present results indicate that higher chilling tolerance in papaya fruit at 1°C could be attributed to more accumulation of sucrose and reducing sugars in relation to more advantageous sugar metabolism. These results provided a basis for explaining the abnormal behavior of papaya fruits in response to varying low temperatures. PRACTICAL APPLICATION: For most chilling-sensitive fruits and vegetables, in the range of temperatures that induce chilling injury (CI), the lower storage temperature may lead to more severe CI. However, as one of the special cases, papaya fruits at 1℃ show slighter CI symptoms than those at higher storage temperature. The reason for this abnormal CI symptom in papaya fruits is that 1°C storage can regulated enzyme activities and changes in gene expression related to sugar metabolism, which could result in more accumulation of sucrose and slower degradation of hexose and contribute to alleviation of CI. Our results provided a basis for explaining the abnormal behavior of papaya fruit in response to varying low temperatures.

Physiological and Transcriptome Analyses of CaCl2 Treatment to Alleviate Chilling Injury in Pineapple.

The post-harvest ripening of pineapples can be effectively postponed by refrigerated storage. Nevertheless, internal browning (IB) frequently appears in pineapples after refrigerated storage during the course of the shelf life at room temperature, which is known as chilling injury (CI). In this study, the chilling injury of pineapple fruit was induced by a low temperature (6 °C) and transferred to normal-temperature storage; the best concentration of 50 µmol/L of CaCl2 was selected by the IB appearance and electrical conductivity. Fruit quality, reactive oxygen species (ROS), antioxidants, and transcription factors were investigated. The physiological data results indicated that pineapples treated with 50 µmol/L of CaCl2 maintained fruit quality, decreased reactive oxygen species (ROS), and enhanced the antioxidant activity of fruits, alleviating internal browning (IB) symptoms in pineapple fruit. The expressions of related genes were also consistent with the physiological changes by the transcriptome data analysis. In addition, we focused on some related metabolic pathways, including phenylpropanoid biosynthesis, MAPK pathway, plant hormone, plant-pathogen interaction, tricarboxylic acid cycle (TAC), and fatty acid biosynthesis. We performed integrative analyses of transcriptome data combined with a series of physiology and experimental analyses on the internal browning of pineapples, which will be of great significance to extending the shelf life of pineapples through molecular biology in the future.

SlBEL11 affects tomato carotenoid accumulation by regulating SlLCY-b2.

Extensive data have demonstrated that carotenoid accumulation in tomato fruit is influenced by environmental cues and hormonal signals. However, there is insufficient information on the mechanism of its transcriptional regulation, as many molecular roles of carotenoid biosynthetic pathways remain unknown. In this work, we found that the silence of the BEL1-like family transcription factor (TF) BEL1-LIKE HOMEODOMAIN 11 (SlBEL11) enhanced carotenoid accumulation in virus induced gene silencing (VIGS) analysis. In its RNA interference (RNAi) transgenic lines, a significant increase in the transcription level for the lycopene beta cyclase 2 (SlLCY-b2) gene was detected, which encoded a key enzyme located at the downstream branch of the carotenoid biosynthetic pathway. In Electrophoretic mobility shift assay (EMSA), SlBEL11 protein was confirmed to bind to the promoter of SlLCY-b2 gene. In addition, the dual-luciferase reporter assay showed its intrinsic transcriptional repression activity. Collectively, our findings added a new member to the carotenoid transcriptional regulatory network and expanded the functions of the SlBEL11 transcription factor.

Enzymatic browning in relation to permeation of oxygen into the kernel of postharvest areca nut under different storage temperatures.

Previous study indicates that kernel of areca nut is susceptible to enzymatic browning caused by phenolic oxidation, which involves the ingression of oxygen into interior tissue. However, the reason for permeation of oxygen into the interior of areca nut and its possible influencing factors (e.g., temperatures) are little known. In the present study, we set three storage temperatures (25, 10, and 5°C) and investigated the effects on kernel browning and related physic-biochemical and tissue morphological changes. The results showed that the most severe kernel browning was observed in areca nut stored at 25°C, followed by 5°C. Comparatively, a slower browning development was found in areca nut stored at 10°C. More serious kernel browning at 25 and 5°C might be attributed to increased membrane permeability and aggravated tissue damage in view of morphological observations on pericarp, mesocarp, and kernel shell. Higher lignin content and phenylalanine ammonia-lyase activity were observed in mesocarp of areca nuts stored at 25 and 5°C as compared to 10°C, indicating that mesocarp lignification could facilitate the permeability of oxygen. Furthermore, the data showed that storage at 25 and 5°C induced the higher polyphenol oxidase activity while accelerating the decline in total phenolic content in areca nut kernel, which could contribute to higher occurrence of enzymatic browning reaction compared to that at 10°C. These results suggest that natural senescence at 25°C and severe chilling stress at 5°C could be influencing factors triggering the permeation of oxygen, leading to internal kernel browning in areca nut.

The Potential Prebiotic Berberine Combined With Methimazole Improved the Therapeutic Effect of Graves' Disease Patients Through Regulating the Intestinal Microbiome.

Graves' disease, a typical metabolism disorder, causes diffuse goiter accompanied by ocular abnormalities and ocular dysfunction. Although methimazole (MI) is a commonly used drug for the treatment of GD, the efficacy of methimazole is only limited to the control of clinical indicators, and the side effects of MI should be seriously considered. Here, we designed a 6-month clinical trial that divided the patients into two groups: a methimazole group (n=8) and a methimazole combined with potential prebiotic berberine group (n=10). The effects of both treatments on thyroid function and treatment outcomes in patients with GD were assessed by thyroid index measurements and gut microbiota metagenomic sequencing. The results showed that the addition of berberine restored the patients' TSH and FT3 indices to normal levels, whereas MI alone restored only FT3. In addition, TRAb was closer to the healthy threshold at the end of treatment with the drug combination. MI alone failed to modulate the gut microbiota of the patients. However, the combination of berberine with methimazole significantly altered the microbiota structure of the patients, increasing the abundance of the beneficial bacteria Lactococcus lactis while decreasing the abundance of the pathogenic bacteria Enterobacter hormaechei and Chryseobacterium indologenes. Furthermore, further mechanistic exploration showed that the addition of berberine resulted in a significant upregulation of the synthesis of enterobactin, which may have increased iron functioning and thus restored thyroid function. In conclusion, methimazole combined with berberine has better efficacy in patients with GD, suggesting the potential benefit of berberine combined with methimazole in modulating the composition of intestinal microbes in the treatment of GD, providing new strong evidence for the effectiveness of combining Chinese and Western drugs from the perspective of modulating the intestinal microbiota.

Probiotic Bifidobacterium longum supplied with methimazole improved the thyroid function of Graves' disease patients through the gut-thyroid axis.

Graves' disease (GD) is an autoimmune disorder that frequently results in hyperthyroidism and other symptoms. Here, we designed a 6-month study with patients divided into three treatment groups, namely, methimazole (MI, n = 8), MI + black bean (n = 9) and MI + probiotic Bifidobacterium longum (n = 9), to evaluate the curative effects of probiotics supplied with MI on thyroid function of patients with GD through clinical index determination and intestinal microbiota metagenomic sequencing. Unsurprisingly, MI intake significantly improved several thyroid indexes but not the most important thyrotropin receptor antibody (TRAb), which is an indicator of the GD recurrence rate. Furthermore, we observed a dramatic response of indigenous microbiota to MI intake, which was reflected in the ecological and evolutionary scale of the intestinal microbiota. In contrast, we did not observe any significant changes in the microbiome in the MI + black bean group. Similarly, the clinical thyroid indexes of patients with GD in the probiotic supplied with MI treatment group continued to improve. Dramatically, the concentration of TRAb recovered to the healthy level. Further mechanistic exploration implied that the consumed probiotic regulated the intestinal microbiota and metabolites. These metabolites impacted neurotransmitter and blood trace elements through the gut-brain axis and gut-thyroid axis, which finally improved the host's thyroid function.

Melatonin Regulates the Neurotransmitter Secretion Disorder Induced by Caffeine Through the Microbiota-Gut-Brain Axis in Zebrafish (Danio rerio).

Melatonin has been widely used as a "probiotic agent" capable of producing strong neurotransmitter secretion regulatory effects, and the microbiota-gut-brain axis-related studies have also highlighted the role of the gut microbiota in neuromodulation. In the present study, a zebrafish neural hyperactivity model was established using caffeine induction to explore the regulatory effects of melatonin and probiotic on neurotransmitter secretion disorder in zebrafish. Disorders of brain neurotransmitter secretion (dopamine, γ-aminobutyric acid, and 5-hydroxytryptamine) caused by caffeine were improved after interference treatment with melatonin or probiotic. Shotgun metagenomic sequencing demonstrated that the melatonin-treated zebrafish gradually restored their normal intestinal microbiota and metabolic pathways. Germ-free (GF) zebrafish were used to verify the essential role of intestinal microbes in the regulation of neurotransmitter secretion. The results of the neurotransmitter and short-chain fatty acid determination revealed that the effect on the zebrafish in the GF group could not achieve that on the zebrafish in the melatonin group after adding the same dose of melatonin. The present research revealed the potential mode of action of melatonin through the microbiota-gut-brain axis to regulate the disruption of neurotransmitter secretion, supporting the future development of psychotropic drugs targeting the intestinal microbiota.