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Abstract Alcohol use disorder has been associated with the development of neurodegenerative diseases, including Alzheimer’s disease (AD). However, recent studies demonstrate that moderate alcohol consumption may be protective against dementia and cognitive decline. We examined astrocyte function, low-density lipoprotein (LDL) receptor-related protein 1 (LRP1), and the NF-κB p65 and IKK-α/β signaling pathways in modulating neuroinflammation and amyloid beta (Aβ) deposition. We assessed apolipoprotein E (ApoE) in the brain of APP/PS1 mice using IHC and ELISA in response to low to moderate ethanol exposure (MEE). First, to confirm the intracerebral distribution of ApoE, we co-stained with GFAP, a marker for astrocytes that biosynthesize ApoE. We sought to investigate whether the ethanol-induced upregulation of LRP1 could potentially inhibit the activity of IL-1β and TNF-α induced IKK-α/β towards NF-κB p65, resulting in a reduction of pro-inflammatory cytokines. To evaluate the actual Aβ load in the brains of APP/PS1 mice, we performed with a specific antibody Aβ (Thioflavin S) on both air- and ethanol-exposed groups, subsequently analyzing Aβ levels. We also measured glucose uptake using 18F- fluorodeoxyglucose (FDG)-positron emission tomography (PET). Finally, we investigated whether MEE induced cognitive and memory changes using the Y maze, noble object recognition test, and Morris water maze. Our findings demonstrate that MEE reduced astrocytic glial fibrillary acidic protein (GFAP) and ApoE levels in the cortex and hippocampus in presymptomatic APP/PS1 mice. Interestingly, increased LRP1 protein expression was accompanied by dampening the IKK-α/β-NF-κB p65 pathway, resulting in decreased IL-1β and TNF-α levels in male mice. Notably, female mice show reduced levels of anti-inflammatory cytokines IL-4, and IL-10 without altering IL-1β and TNF-α concentrations. In both males and females, Aβ plaques, a hallmark of AD, were reduced in the cortex and hippocampus of APP/PS1 mice exposed to ethanol starting at pre-symptomatic stage. Consistently, MEE increased FDG-PET-based brain activities and normalized cognitive and memory deficits in the APP/PS1 mice. Our findings suggest that MEE may benefit AD pathology via modulating LRP1 expression, potentially reducing neuroinflammation and attenuating Aβ deposition. Our study implies that reduced astrocyte-derived ApoE and LDL cholesterol levels are critical for attenuating AD pathology.

Abstract Impaired ion channels regulating Golgi pH lead to structural alterations in the Golgi apparatus, such as fragmentation, which is found, along with cognitive impairment, in Alzheimer’s disease. However, the causal relationship between altered Golgi structure and cognitive impairment remains elusive due to the lack of understanding of ion channels in the Golgi apparatus of brain cells. Here, we identify that a transmembrane protein TMEM87A, renamed Golgi-pH-regulating cation channel (GolpHCat), expressed in astrocytes and neurons that contributes to hippocampus-dependent memory. We find that GolpHCat displays unique voltage-dependent currents, which is potently inhibited by gluconate. Additionally, we gain structural insights into the ion conduction through GolpHCat at the molecular level by determining three high-resolution cryogenic-electron microscopy structures of human GolpHCat. GolpHCat-knockout mice show fragmented Golgi morphology and altered protein glycosylation and functions in the hippocampus, leading to impaired spatial memory. These findings suggest a molecular target for Golgi-related diseases and cognitive impairment.

Abstract Background Transmembrane 4 L six family member 5 (TM4SF5) translocates subcellularly and functions metabolically, although it is unclear how intracellular TM4SF5 translocation is linked to metabolic contexts. It is thus of interests to understand how the traffic dynamics of TM4SF5 to subcellular endosomal membranes are correlated to regulatory roles of metabolisms. Methods Here, we explored the metabolic significance of TM4SF5 localization at mitochondria‐lysosome contact sites (MLCSs), using in vitro cells and in vivo animal systems, via approaches by immunofluorescence, proximity labelling based proteomics analysis, organelle reconstitution etc. Results Upon extracellular glucose repletion following depletion, TM4SF5 became enriched at MLCSs via an interaction between mitochondrial FK506‐binding protein 8 (FKBP8) and lysosomal TM4SF5. Proximity labeling showed molecular clustering of phospho‐dynamic‐related protein I (DRP1) and certain mitophagy receptors at TM4SF5‐enriched MLCSs, leading to mitochondrial fission and autophagy. TM4SF5 bound NPC intracellular cholesterol transporter 1 (NPC1) and free cholesterol, and mediated export of lysosomal cholesterol to mitochondria, leading to impaired oxidative phosphorylation but intact tricarboxylic acid (TCA) cycle and β‐oxidation. In mouse models, hepatocyte Tm4sf5 promoted mitophagy and cholesterol transport to mitochondria, both with positive relations to liver malignancy. Conclusions Our findings suggested that TM4SF5‐enriched MLCSs regulate glucose catabolism by facilitating cholesterol export for mitochondrial reprogramming, presumably while hepatocellular carcinogenesis, recapitulating aspects for hepatocellular carcinoma metabolism with mitochondrial reprogramming to support biomolecule synthesis in addition to glycolytic energetics.

Abstract Background Malignant glioma is among the most lethal and frequently occurring brain tumors, and the average survival period is 15 months. Existing chemotherapy has low tolerance and low blood-brain barrier (BBB) permeability; therefore, the required drug dose cannot be accurately delivered to the tumor site, resulting in an insufficient drug effect. Methods Herein, we demonstrate a precision photodynamic tumor therapy using a photosensitizer (ZnPcS) capable of binding to albumin in situ, which can increase the permeability of the BBB and accurately target glioma. Albumin-binding ZnPcS was designed to pass through the BBB and bind to secreted protein acidic and rich in cysteine (SPARC), which is abundant in the glioma plasma membrane. Results When the upper part of a mouse brain was irradiated using a laser (0.2 W cm− 2) after transplantation of glioma and injection of ZnPcS, tumor growth was inhibited by approximately 83.6%, and the 50% survival rate of the treatment group increased by 14 days compared to the control group. In glioma with knockout SPARC, the amount of ZnPcS entering the glioma was reduced by 63.1%, indicating that it can target glioma through the SPARC pathway. Conclusion This study showed that the use of albumin-binding photosensitizers is promising for the treatment of malignant gliomas. Graphical Abstract

G-protein coupled receptors (GPCRs) present specific activation pathways and signaling among receptor subtypes. Hence, an extensive knowledge of the structural dynamics of the receptor is critical for the development of therapeutics. Here, we target the adenosine A1 receptor (A1R), for which a negligible number of drugs have been approved. We combine molecular dynamics simulations, enhanced sampling techniques, network theory, and pocket detection to decipher the activation pathway of A1R, decode the allosteric networks, and identify transient pockets. The A1R activation pathway reveals hidden intermediate and pre-active states together with the inactive and fully-active states observed experimentally. The protein energy networks computed throughout these conformational states successfully unravel the extra and intracellular allosteric centers and the communication pathways that couple them. We observe that the allosteric networks are dynamic, being increased along activation and fine-tuned in the presence of the trimeric G-proteins. Overlap of transient pockets and energy networks uncovers how the allosteric coupling between pockets and distinct functional regions of the receptor is altered along activation. Through an in-depth analysis of the bridge between the activation pathway, energy networks, and transient pockets, we provide a further understanding of A1R. This information can be useful to ease the design of allosteric modulators for A1R.

Ototoxicity is the drug-induced damage of the inner ear, causing bilateral irreversible sensorineural hearing loss. Cisplatin is a widely used chemotherapeutic agent which causes ototoxicity as its side effect. Pretreatment with metformin prior to the application of cisplatin significantly decreased the late apoptosis and attenuated the cisplatin-induced increase in ROS. To understand the molecular mechanisms that are involved in the preventive effect of metformin, we evaluated the change of gene expression induced by cisplatin at several different time points (0 h, 6 h, 15 h, 24 h and 48 h) and the alteration of gene expression according to pretreatment with metformin in HEI-OC1 cells through microarray analysis. Cisplatin exposure induced a total of 89 DEGs (differentially expressed genes) after 6 h, with a total of 433 DEGs after 15 h, a total of 941 DEGs after 24 h, and a total of 2764 DEGs after 48 h. When cells were pretreated with metformin for 24 h, we identified a total of 105 DEGs after 6 h of cisplatin exposure, a total of 257 DEGs after 15 h, a total of 1450 DEGs after 24 h, and a total of 1463 DEGs after 48 h. The analysis was performed based on the gene expression, network analyses, and qRT-PCR, and we identified several genes (CSF2, FOS, JUN, TNFα, NFκB, Txnip, ASK1, TXN2, ATF3, TP53, IL6, and IGF1) as metformin-related preventive biomarkers in cisplatin ototoxicity.

Background: Organized hematoma in the sphenoid sinus is rare, but serious complications, such as visual deficits, can occur. Three such case reports have been published previously in the literature; however, none have achieved complete recovery of the vision. Case presentation: A 69-year-old male patient was referred to the ear, nose, and throat department with an expansile soft tissue mass filling the right sphenoid sinus and blurry vision in his right eye. Complete mass removal was achieved by a wide opening of the sphenoid sinus via an endoscopic transsphenoidal approach, followed by cauterization of the feeding artery and coverage by a nasoseptal flap. The patient’s vision was restored after the operation, and he declared no visual symptoms until the latest follow-up (one year after the surgery). Conclusions: Complete excision with an endoscopic endonasal transsphenoidal approach can restore visual deterioration caused by a sphenoid sinus organized hematoma.

Alcohol use disorder (AUD) is characterized as a chronic, relapsing disease with a pattern of excessive drinking despite negative consequences to an individual’s life. Severe chronic alcohol use impairs the function of the medial prefrontal cortex (mPFC), which contributes to alcohol-induced cognitive and executive dysfunction. The mPFC contains more mitochondria compared to other cortical areas, which suggests mitochondrial damage may occur in AUD and trigger subsequent behavior change. Here, we identified morphological and functional changes in mitochondria in the mPFC in C57BL6/J mice after 8 h of withdrawal from chronic intermittent alcohol (CIA) exposure. Three-dimensional serial block-face scanning electron microscopy (SBFSEM) reconstruction revealed that CIA exposure elongated mPFC mitochondria and formed mitochondria-on-a-string (MOAS). Furthermore, alcohol significantly affected mitochondrial bioenergetics, including oxidative phosphorylation and electron transport, with inhibited aerobic respiration in mPFC mitochondria after CIA exposure. We also found decreased expression of fusion (mitofusin 2, Mfn2) and increased fission (mitochondrial fission 1 protein, Fis1) proteins in the mPFC of alcohol-treated mice. In sum, our study suggests that CIA exposure impairs mitochondrial dynamics and function in the mPFC.

The new advances in deep learning methods have influenced many aspects of scientific research, including the study of the protein system. The prediction of proteins’ 3D structural components is now heavily dependent on machine learning techniques that interpret how protein sequences and their homology govern the inter-residue contacts and structural organization. Especially, methods employing deep neural networks have had a significant impact on recent CASP13 and CASP14 competition. Here, we explore the recent applications of deep learning methods in the protein structure prediction area. We also look at the potential opportunities for deep learning methods to identify unknown protein structures and functions to be discovered and help guide drug–target interactions. Although significant problems still need to be addressed, we expect these techniques in the near future to play crucial roles in protein structural bioinformatics as well as in drug discovery.

G protein-coupled receptor (GPCR) oligomerization, while contentious, continues to attract the attention of researchers. Numerous experimental investigations have validated the presence of GPCR dimers, and the relevance of dimerization in the effectuation of physiological functions intensifies the attractiveness of this concept as a potential therapeutic target. GPCRs, as a single entity, have been the main source of scrutiny for drug design objectives for multiple diseases such as cancer, inflammation, cardiac, and respiratory diseases. The existence of dimers broadens the research scope of GPCR functions, revealing new signaling pathways that can be targeted for disease pathogenesis that have not previously been reported when GPCRs were only viewed in their monomeric form. This review will highlight several aspects of GPCR dimerization, which include a summary of the structural elucidation of the allosteric modulation of class C GPCR activation offered through recent solutions to the three-dimensional, full-length structures of metabotropic glutamate receptor and γ-aminobutyric acid B receptor as well as the role of dimerization in the modification of GPCR function and allostery. With the growing influence of computational methods in the study of GPCRs, we will also be reviewing recent computational tools that have been utilized to map protein–protein interactions (PPI).

Molecular dynamics (MD) simulation is a rigorous theoretical tool that when used efficiently could provide reliable answers to questions pertaining to the structure-function relationship of proteins. Data collated from protein dynamics can be translated into useful statistics that can be exploited to sieve thermodynamics and kinetics crucial for the elucidation of mechanisms responsible for the modulation of biological processes such as protein-ligand binding and protein-protein association. Continuous modernization of simulation tools enables accurate prediction and characterization of the aforementioned mechanisms and these qualities are highly beneficial for the expedition of drug development when effectively applied to structure-based drug design (SBDD). In this review, current all-atom MD simulation methods, with focus on enhanced sampling techniques, utilized to examine protein structure, dynamics, and functions are discussed. This review will pivot around computer calculations of protein-ligand and protein-protein systems with applications to SBDD. In addition, we will also be highlighting limitations faced by current simulation tools as well as the improvements that have been made to ameliorate their efficiency.

G protein-coupled receptors (GPCRs) are major drug targets due to their ability to facilitate signal transduction across cell membranes, a process that is vital for many physiological functions to occur. The development of computational technology provides modern tools that permit accurate studies of the structures and properties of large chemical systems, such as enzymes and GPCRs, at the molecular level. The advent of multiscale molecular modeling permits the implementation of multiple levels of theories on a system of interest, for instance, assigning chemically relevant regions to high quantum mechanics (QM) level of theory while treating the rest of the system using classical force field (molecular mechanics (MM) potential). Multiscale QM/MM molecular modeling have far-reaching applications in the rational design of GPCR drugs/ligands by affording precise ligand binding configurations through the consideration of conformational plasticity. This enables the identification of key binding site residues that could be targeted to manipulate GPCR function. This review will focus on recent applications of multiscale QM/MM molecular simulations in GPCR studies that could boost the efficiency of future structure-based drug design (SBDD) strategies.

The primary goal of rational drug discovery is the identification of selective ligands which act on single or multiple drug targets to achieve the desired clinical outcome through the exploration of total chemical space. To identify such desired compounds, computational approaches are necessary in predicting their drug-like properties. G Protein-Coupled Receptors (GPCRs) represent one of the largest and most important integral membrane protein families. These receptors serve as increasingly attractive drug targets due to their relevance in the treatment of various diseases, such as inflammatory disorders, metabolic imbalances, cardiac disorders, cancer, monogenic disorders, etc. In the last decade, multitudes of three-dimensional (3D) structures were solved for diverse GPCRs, thus referring to this period as the “golden age for GPCR structural biology.” Moreover, accumulation of data about the chemical properties of GPCR ligands has garnered much interest toward the exploration of GPCR chemical space. Due to the steady increase in the structural, ligand, and functional data of GPCRs, several cheminformatics approaches have been implemented in its drug discovery pipeline. In this review, we mainly focus on the cheminformatics-based paradigms in GPCR drug discovery. We provide a comprehensive view on the ligand– and structure-based cheminformatics approaches which are best illustrated via GPCR case studies. Furthermore, an appropriate combination of ligand-based knowledge with structure-based ones, i.e., integrated approach, which is emerging as a promising strategy for cheminformatics-based GPCR drug design is also discussed.

Background: Accumulating evidence indicates that cognitive remediation (CR) is effective for improving various cognitive deficits in adult patients with schizophrenia. Although reports of brain plasticity in older adults and the service needs for chronic patients with schizophrenia are increasing, very few randomized controlled trials of CR have been conducted in middle-aged or older inpatients with chronic schizophrenia. We investigated the efficacy of individualized CR on the cognitive impairments of middle-aged or older inpatients with chronic schizophrenia within the context of comprehensive psychiatric rehabilitation (PR) by comparing the results obtained with PR only and treatment as usual (TAU).Method: Fifty-seven middle-aged and older individuals with chronic schizophrenia and mild to moderate cognitive deficits were enrolled. Thirty-eight who were undergoing PR were randomly assigned to CR + PR (N = 19) or PR-only (N = 19) groups. Nineteen participants who were undergoing TAU without CR or PR were evaluated pre- and post-treatment.Results: CR was easily provided and well received (drop-out rates = 5.3%) by middle-aged or older psychiatric inpatients. Compared to the PR-Only or TAU patients, patients in the CR + PR group showed greater improvement in executive functioning. Compared to TAU patients, CR + PR and PR-only patients showed greater improvement in logical memory. More patients in the CR + PR group improved clinically significantly in executive functioning and logical memory, compared with the PR-only and TAU patients.Conclusions: These results suggested that CR improved some cognitive deficits in middle-aged or older inpatients with chronic schizophrenia and that it was effective as an adjunctive treatment to the usual PR services provided in inpatient settings.Clinical Registration: KCT0002609

The advent of advanced molecular modeling software, big data analytics, and high-speed processing units has led to the exponential evolution of modern drug discovery and better insights into complex biological processes and disease networks. This has progressively steered current research interests to understanding protein-protein interaction (PPI) systems that are related to a number of relevant diseases, such as cancer, neurological illnesses, metabolic disorders, etc. However, targeting PPIs are challenging due to their “undruggable” binding interfaces. In this review, we focus on the current obstacles that impede PPI drug discovery, and how recent discoveries and advances in in silico approaches can alleviate these barriers to expedite the search for potential leads, as shown in several exemplary studies. We will also discuss about currently available information on PPI compounds and systems, along with their usefulness in molecular modeling. Finally, we conclude by presenting the limits of in silico application in drug discovery and offer a perspective in the field of computer-aided PPI drug discovery.

Dynamics and functions of G-protein coupled receptors (GPCRs) are accurately regulated by the type of ligands that bind to the orthosteric or allosteric binding sites. To glean the structural and dynamical origin of ligand-dependent modulation of GPCR activity, we performed total ~ 5 μsec molecular dynamics simulations of A2A adenosine receptor (A2AAR) in its apo, antagonist-bound, and agonist-bound forms in an explicit water and membrane environment, and examined the corresponding dynamics and correlation between the 10 key structural motifs that serve as the allosteric hotspots in intramolecular signaling network. We dubbed these 10 structural motifs "binary switches" as they display molecular interactions that switch between two distinct states. By projecting the receptor dynamics on these binary switches that yield 2(10) microstates, we show that (i) the receptors in apo, antagonist-bound, and agonist-bound states explore vastly different conformational space; (ii) among the three receptor states the apo state explores the broadest range of microstates; (iii) in the presence of the agonist, the active conformation is maintained through coherent couplings among the binary switches; and (iv) to be most specific, our analysis shows that W246, located deep inside the binding cleft, can serve as both an agonist sensor and actuator of ensuing intramolecular signaling for the receptor activation. Finally, our analysis of multiple trajectories generated by inserting an agonist to the apo state underscores that the transition of the receptor from inactive to active form requires the disruption of ionic-lock in the DRY motif.

DNA methylation is an epigenetic modification that regulates gene expression by DNA methyltransferases (DNMTs). Inhibition of DNMTs is a promising approach for cancer therapy. Recently, novel classes of the quinolone-based compound, SGI-1027, and RG108-procainamide conjugates, CBC12, have been identified as potent DNMT inhibitors. In this work, we report comprehensive studies using induced-fit docking of SGI-1027 and CBC12 with human DNMT1 and DNMT3A. The docking was performed in the C-terminal MTase catalytic domain, which contains the substrate and cofactor binding sites, in the presence and absence of other domains. Induced-fit docking predicts possible binding modes of the ligands through the appropriate structural changes in the receptor. This work suggests a hypothesis of the inhibitory mechanisms of the new inhibitors which is in agreement with the reported autoinhibitory mechanism. The insights obtained in this work can be used to design DNMT inhibitors with novel scaffolds.

Capsaicin is the most predominant and naturally occurring alkamide found in Capsicum fruits. Since its discovery in the 19th century, the therapeutic roles of capsaicin have been well characterized. The potential applications of capsaicin range from food flavorings to therapeutics. Indeed, capsaicin and few of its analogues have featured in clinical research covered by more than a thousand patents. Previous records suggest pleiotropic pharmacological activities of capsaicin such as an analgesic, anti-obesity, anti-pruritic, anti-inflammatory, anti-apoptotic, anti-cancer, anti-oxidant, and neuro-protective functions. Moreover, emerging data indicate its clinical significance in treating vascular-related diseases, metabolic syndrome, and gastro-protective effects. The dearth of potent drugs for management of such disorders necessitates the urge for further research into the pharmacological aspects of capsaicin. This review summarizes the historical background, source, structure and analogues of capsaicin, and capsaicin-triggered TRPV1 signaling and desensitization processes. In particular, we will focus on the therapeutic roles of capsaicin and its analogues in both normal and pathophysiological conditions.

Human leukotriene A4 hydrolase (hLTA4H), which is the final and rate-limiting enzyme of arachidonic acid pathway, converts the unstable epoxide LTA4 to a proinflammatory lipid mediator LTB4 through its hydrolase function. The LTA4H is a bi-functional enzyme that also exhibits aminopeptidase activity with a preference over arginyl tripeptides. Various mutations including E271Q, R563A, and K565A have completely or partially abolished both the functions of this enzyme. The crystal structures with these mutations have not shown any structural changes to address the loss of functions. Molecular dynamics simulations of LTA4 and tripeptide complex structures with functional mutations were performed to investigate the structural and conformation changes that scripts the observed differences in catalytic functions. The observed protein-ligand hydrogen bonds and distances between the important catalytic components have correlated well with the experimental results. This study also confirms based on the structural observation that E271 is very important for both the functions as it holds the catalytic metal ion at its location for the catalysis and it also acts as N-terminal recognition residue during peptide binding. The comparison of binding modes of substrates revealed the structural changes explaining the importance of R563 and K565 residues and the required alignment of substrate at the active site. The results of this study provide valuable information to be utilized in designing potent hLTA4H inhibitors as anti-inflammatory agents.

Background: The adequate dose of levothyroxine (LT4) for patients who have undergone total thyroidectomy (TT) for differentiated thyroid cancer (DTC) is uncertain. We evaluated the LT4 dose required to achieve mild thyroid-stimulating hormone (TSH) suppression in DTC patients after TT. Methods: The electronic medical records of patients who underwent TT for DTC and received mild TSH suppression therapy were reviewed. Linear regression analysis was performed to evaluate the association between LT4 dose (µg/kg) and an ordinal group divided by body mass index (BMI). We also evaluated the trend in LT4 doses among groups divided by BMI and age. Results: In total, 123 patients achieved mild TSH suppression (0.1 to 0.5 mIU/L). The BMI variable was divided into three categories: <23 kg/m2 (n=46), =23 and <25 kg/m2 (n=30), and =25 kg/m2 (n=47). In the linear regression analysis, BMI was negatively associated with the LT4 dose after adjusting for age and sex (P<0.001). The LT4 doses required to achieve mild TSH suppression based on the BMI categories were 1.86, 1.71, and 1.71 µg/kg, respectively (P for trend <0.001). Further analysis with groups divided by age and BMI revealed that a higher BMI was related to a lower LT4 dose, especially in younger patients aged 20 to 39 (P for trend=0.011). Conclusion: The study results suggest an appropriate LT4 dose for mild TSH suppression after TT based on body weight in patients with DTC. Considering body weight, BMI, and age in estimating LT4 doses might help to achieve the target TSH level promptly. [ABSTRACT FROM AUTHOR]

Background/Aims: This study aims to investigate the effect of a fermented rice drink with Lactiplantibacillus plantarum JSA22 on symptoms, blood tests, microbiomes, and fecal metabolites in patients with irritable bowel syndrome (IBS) who were overweight. Methods: Sixty overweight (body mass index = 23 kg/m2) patients aged between 20 and 65 with IBS were enrolled. Patients were divided into 2 groups and administered either a fermented rice drink or an nonfermented rice drink for a month. The symptom questionnaire, blood samples, and stool samples for microbiome and metabolite were collected before and after the month of rice drink administration. The primary efficacy variable was the subject's global assessment of IBS symptoms. Results:In both groups, global IBS symptoms, including abdominal pain, bowel habit, urgency, and abdominal distension, improved significantly (P < 0.01). The abdominal bloating was more significantly improved in the fermented rice drink group than in the nonfermented rice drink group (P < 0.05). Significant changes were not observed in metabolic syndrome-related blood tests or fecal metabolites in either group. However, microbiome analysis showed significant differences in genus levels before and after consuming fermented rice drink, such as in Blautia in stool (P = 0.020) and Prevotella (P = 0.017) and Oribacterium (P = 0.018) in saliva. Conclusions: The fermented rice drink with L. plantarum JSA22 showed a beneficial effect in reducing abdominal distension in IBS patients. Bacteria that reduce visceral fat accumulation increased in the stool and saliva of patients who consumed fermented rice drinks. [ABSTRACT FROM AUTHOR]

Objective: Some patients with disc herniation who underwent discectomy complain of back pain after surgery and are unsatisfied with the surgical results. This study aimed to evaluate the relationship between preoperative disc height (DH), postoperative DH, and pain score 12 months after surgery in patients who underwent microdiscectomy for herniated lumbar disc. Methods: This study enrolled patients who underwent microdiscectomy at a medical center between January 2012 and December 2020. Patients with X-ray or computed tomography and pain score assessment (visual analog scale score) prior to surgery, immediately post-op, and at 1, 6, and 12 months after surgery were included. The DH index was defined as DH/overlying vertebral width. The DH ratio was defined as the postoperative DH/preoperative DH. Simple linear regression and multivariate linear regression analyses were applied to assess the correlation between DHs and leg pain scores 12 months after surgery. Results: A total of 118 patients who underwent microdiscectomy were included. DH decreased up to 12 months after surgery. The DH ratio at 1, 6, and 12 months after discectomy showed a significant positive correlation with the pain scores at 12 months after discectomy (1 month: p=0.045, B=0.52; 6 months: p=0.008, B=0.78; 12 months: p=0.005, B=0.69). Multivariate linear regression analysis revealed that the level of surgery, sex, age, and body mass index had no significant relationship with back pain scores after 12 months. Conclusion: In patients who underwent microdiscectomy, the DH ratios at 1, 6, and 12 months after surgery were prognostic factors for back pain scores at 12 months after surgery. Aggressive discectomy is recommended for lower postoperative DH ratios and Visual analog scale scores, leading to improved patient satisfaction. [ABSTRACT FROM AUTHOR]