Neprilysin inhibitors and risk of Alzheimer's disease: A future perspective.

Alzheimer's disease (AD) is a heterogeneous neurodegenerative disease with multifaceted neuropathological disorders. AD is characterized by intracellular accumulation of phosphorylated tau proteins and extracellular deposition of amyloid beta (Aß). Various protease enzymes, including neprilysin (NEP), are concerned with the degradation and clearance of Aß. Indeed, a defective neuronal clearance pathway due to the dysfunction of degradation enzymes might be a possible mechanism for the accumulation of Aß and subsequent progression of AD neuropathology. NEP is one of the most imperative metalloproteinase enzymes involved in the clearance of Aß. This review aimed to highlight the possible role of NEP inhibitors in AD. The combination of sacubitril and valsartan which is called angiotensin receptor blocker and NEP inhibitor (ARNI) may produce beneficial and deleterious effects on AD neuropathology. NEP inhibitors might increase the risk of AD by the inhibition of Aß clearance, and increase brain bradykinin (BK) and natriuretic peptides (NPs), which augment the pathogenesis of AD. These verdicts come from animal model studies, though they may not be applied to humans. However, clinical studies revealed promising safety findings regarding the use of ARNI. Moreover, NEP inhibition increases various neuroprotective peptides involved in inflammation, glucose homeostasis and nerve conduction. Also, NEP inhibitors may inhibit dipeptidyl peptidase 4 (DPP4) expression, ameliorating insulin and glucagon-like peptide 1 (GLP-1) levels. These findings proposed that NEP inhibitors may have a protective effect against AD development by increasing GLP-1, neuropeptide Y (NPY) and substance P, and deleterious effects by increasing brain BK. Preclinical and clinical studies are recommended in this regard.

Cerebrospinal fluid immunoglobulins in primary progressive multiple sclerosis are pathogenic.

Multiple sclerosis is clinically characterized by relapses and remissions (relapsing-remitting multiple sclerosis) that over time may evolve to a progressive course (secondary progressive multiple sclerosis) or as having a progressive course from disease onset (primary progressive multiple sclerosis). At present, it is not definitively known whether these clinical entities constitute a single pathological disease or whether these manifestations represent two distinct disease entities sharing inflammatory demyelination as a pathological feature. Here we show using a novel mouse model that CSF of primary progressive multiple sclerosis patients is unique in its capacity to induce motor disability and spinal cord pathology including demyelination, impaired remyelination, reactive astrogliosis and axonal damage. Notably, removal of immunoglobulin G from primary progressive multiple sclerosis CSF via filtration or immunodepletion attenuates its pathogenic capacity. Furthermore, injection of recombinant antibodies derived from primary progressive multiple sclerosis CSF recapitulates the pathology. Our findings suggest that the clinical and pathological features of primary progressive multiple sclerosis are antibody-mediated and pathogenically distinct from relapsing-remitting and secondary progressive multiple sclerosis. Our study has potentially important implications for the development of specific therapies for patients with primary progressive multiple sclerosis.

Machine learning-based classification of structured light modes under turbulence and eavesdropping effects.

This paper considers the classification of multiplexed structured light modes, aiming to bolster communication reliability and data transfer rates, particularly in challenging scenarios marked by turbulence and potential eavesdropping. An experimental free-space optic (FSO) system is established to transmit 16 modes [8-ary Laguerre Gaussian (LG) and 8-ary superposition LG (Mux-LG) mode patterns] over a 3-m FSO channel, accounting for interception threats and turbulence effects. To the best of authors' knowledge, this paper is the first to consider both factors concurrently. We propose four machine/deep learning algorithms-artificial neural network, support vector machine, 1D convolutional neural network, and 2D convolutional neural network-for classification purposes. By fusing the outputs of these methods, we achieve promising classification results exceeding 92%, 81%, and 69% in cases of weak, moderate, and strong turbulence, respectively. Structured light modes exhibit significant potential for a variety of real-world applications where reliable and high-capacity data transmission is crucial.

Synergistic Effect of Nilavembu Choornam-Gold Nanoparticles on Antibiotic-Resistant Bacterial Susceptibility and Contact Lens Contamination-Associated Infectious Pathogenicity.

Antibiotic-resistant bacterial colonies mitigate rapid biofilm formation and have complex cell wall fabrications, making it challenging to penetrate drugs across their biofilm barriers. The objective of this study was to investigate the antibacterial susceptibility of antibiotic-resistant bacteria and contact lens barrenness. Nilavembu Choornam-Gold Nanoparticles (NC-GNPs) were synthesized using NC polyherbal extract and characterized by UV-visible spectrophotometer, SEM-EDX, XRD, Zeta sizer, FTIR, and TEM analysis. Contact lenses with overnight cultures of antibiotic-resistant bacteria K. pneumoniae and S. aureus showed significant differences in growth, biofilm formation, and infection pathogenicity. The NC-GNPs were observed in terms of size (average size is 57.6 nm) and surface chemistry. A zone of inhibition was calculated for K. pneumoniae 18.8 ± 1.06, S. aureus 23.6 ± 1.15, P. aeruginosa 24.16 ± 0.87, and E. faecalis 24.5 ± 1.54 mm at 24 h of NC-GNPs alone treatment. In electron microscopy studies, NC-GNP-treated groups showed nuclear shrinkage, nuclear disintegration, degeneration of cell walls, and inhibited chromosomal division. In contrast, normal bacterial colonies had a higher number of cell divisions and routinely migrated toward cell multiplications. NC-GNPs exhibited antibacterial efficacy against antibiotic-resistant bacteria when compared to NC extract alone. We suggest that NC-GNPs are highly valuable to the population of hospitalized patients and other people to reduce the primary complications of contact lens contamination-oriented microbial infection and the therapeutic efficiency of antibiotic-resistant bacterial pathogenicity.

Endovascular thrombectomy for acute ischemic stroke in Saudi Arabia: A single-center experience.

PURPOSE: This study aimed to investigate the outcomes of endovascular thrombectomy-treated patients in King Fahad Medical City, Riyadh, Saudi Arabia. METHODS: A retrospective cohort study of acute ischemic stroke patients treated with endovascular thrombectomy. Patients were included in the study between January 2015 and December 2022. Good outcomes were defined as a modified Rankin Scale (mRS) of 0-2 at 90 days. Multivariate logistic regression analysis was performed to identify the independent factors associated with good outcomes. RESULTS: During the study period, 369 patients with acute ischemic stroke (mean ± SD age, 61/- 15.1 yrs; 55.4 % male) underwent mechanical thrombectomy. Median National Institute of Health Stroke Scale (NIHSS) 15. Intravenous thrombolysis was administered to 34.5 % of the patients. Successful recanalization in the anterior circulation was achieved in 84.8 % of patients. Data from mRS performed after 90 days in the anterior circulation were available for 71.2 % of the patients. Of these, 41 % showed a good outcome, and the mortality rate was 22.4 %. The significant factors associated with good outcomes were age, NIHSS score, Alberta Stroke Program Early Computed Tomography Score (ASPECTS), and short arterial puncture to recanalization. CONCLUSION: The number of patients who underwent endovascular thrombectomy has increased over time. The treatment outcomes and mortality were comparable with those of previous endovascular thrombectomy registries despite the high prevalence of DM, lower ASPECT score, and prolonged onset-to-recanalization time.

New insights on the potential anti-epileptic effect of metformin: Mechanistic pathway.

Epilepsy is a chronic neurological disease characterized by recurrent seizures. Epilepsy is observed as a well-controlled disease by anti-epileptic agents (AEAs) in about 69%. However, 30%-40% of epileptic patients fail to respond to conventional AEAs leading to an increase in the risk of brain structural injury and mortality. Therefore, adding some FDA-approved drugs that have an anti-seizure activity to the anti-epileptic regimen is logical. The anti-diabetic agent metformin has anti-seizure activity. Nevertheless, the underlying mechanism of the anti-seizure activity of metformin was not entirely clarified. Henceforward, the objective of this review was to exemplify the mechanistic role of metformin in epilepsy. Metformin has anti-seizure activity by triggering adenosine monophosphate-activated protein kinase (AMPK) signalling and inhibiting the mechanistic target of rapamycin (mTOR) pathways which are dysregulated in epilepsy. In addition, metformin improves the expression of brain-derived neurotrophic factor (BDNF) which has a neuroprotective effect. Hence, metformin via induction of BDNF can reduce seizure progression and severity. Consequently, increasing neuronal progranulin by metformin may explain the anti-seizure mechanism of metformin. Also, metformin reduces α-synuclein and increases protein phosphatase 2A (PPA2) with modulation of neuroinflammation. In conclusion, metformin might be an adjuvant with AEAs in the management of refractory epilepsy. Preclinical and clinical studies are warranted in this regard.

PRSS8, encoding prostasin, is mutated in patients with autosomal recessive ichthyosis.

Ichthyosis is a genetically heterogeneous genodermatosis characterized by severely rough, dry and scaly skin. We report two consanguineous families with congenital ichthyosis. Combined positional mapping and exome sequencing of the two families revealed novel homozygous likely deleterious variants in PRSS8 (encoding prostasin) within a linkage locus on chromosome 16. One variant involved a canonical splice site and was associated with reduced abundance of the normal transcript, while the other was a missense variant that altered a highly conserved residue. The phenotype of Prss8 knockout mouse bears a striking resemblance to the one we describe in human patients, including the skin histopathology. Our data suggest a novel PRSS8-related ichthyosis disorder.

Autophagy and autophagy signaling in Epilepsy: possible role of autophagy activator.

Autophagy is an explicit cellular process to deliver dissimilar cytoplasmic misfolded proteins, lipids and damaged organelles to the lysosomes for degradation and elimination. The mechanistic target of rapamycin (mTOR) is the main negative regulator of autophagy. The mTOR pathway is involved in regulating neurogenesis, synaptic plasticity, neuronal development and excitability. Exaggerated mTOR activity is associated with the development of temporal lobe epilepsy, genetic and acquired epilepsy, and experimental epilepsy. In particular, mTOR complex 1 (mTORC1) is mainly involved in epileptogenesis. The investigation of autophagy's involvement in epilepsy has recently been conducted, focusing on the critical role of rapamycin, an autophagy inducer, in reducing the severity of induced seizures in animal model studies. The induction of autophagy could be an innovative therapeutic strategy in managing epilepsy. Despite the protective role of autophagy against epileptogenesis and epilepsy, its role in status epilepticus (SE) is perplexing and might be beneficial or detrimental. Therefore, the present review aims to revise the possible role of autophagy in epilepsy.

Primary Hypothyroidism and Alzheimer's Disease: A Tale of Two.

Hypothyroidism (HPT) HPT could be a risk factor for the development and progression of Alzheimer's disease (AD). In addition, progressive neurodegeneration in AD may affect the metabolism of thyroid hormones (THs) in the brain causing local brain HPT. Hence, the present review aimed to clarify the potential association between HPT and AD. HPT promotes the progression of AD by inducing the production of amyloid beta (Aß) and tau protein phosphorylation with the development of synaptic plasticity and memory dysfunction. Besides, the metabolism of THs is dysregulated in AD due to the accumulation of Aß and tau protein phosphorylation leading to local brain HPT. Additionally, HPT can affect AD neuropathology through various mechanistic pathways including dysregulation of transthyretin, oxidative stress, ER stress, autophagy dysfunction mitochondrial dysfunction, and inhibition of brain-derived neurotrophic factor. Taken together there is a potential link between HPT and AD, as HPT adversely impacts AD neuropathology and the reverse is also true.

Molecular mechanisms on how FABP5 inhibitors promote apoptosis-induction sensitivity of prostate cancer cells.

Previous work showed that FABP5 inhibitors suppressed the malignant progression of prostate cancer cells, and this suppression might be achieved partially by promoting apoptosis. But the mechanisms involved were not known. Here, we investigated the effect of inhibitors on apoptosis and studied the relevant mechanisms. WtrFABP5 significantly reduced apoptotic cells in 22Rv1 and PC3 by 18% and 42%, respectively. In contrast, the chemical inhibitor SB-FI-26 produced significant increases in percentages of apoptotic cells in 22Rv1 and PC3 by 18.8% (±4.1) and 4.6% (±1.1), respectively. The bio- inhibitor dmrFABP5 also did so by 23.1% (±2.4) and 15.8% (±3.0), respectively, in these cell lines. Both FABP5 inhibitors significantly reduced the levels of the phosphorylated nuclear fatty acid receptor PPARγ, indicating that these inhibitors promoted apoptosis-induction sensitivity of the cancer cells by suppressing the biological activity of PPARγ. Thus, the phosphorylated PPARγ levels were reduced by FABP5 inhibitors, the levels of the phosphorylated AKT and activated nuclear factor kapper B (NFκB) were coordinately altered by additions of the inhibitors. These changes eventually led to the increased levels of cleaved caspase-9 and cleaved caspase-3; and thus, increase in the percentage of cells undergoing apoptosis. In untreated prostate cancer cells, increased FABP5 suppressed the apoptosis by increasing the biological activity of PPARγ, which, in turn, led to a reduced apoptosis by interfering with the AKT or NFκB signaling pathway. Our results suggested that the FABP5 inhibitors enhanced the apoptosis-induction of prostate cancer cells by reversing the biological effect of FABP5 and its related pathway.

Effects of prenatal exercise on gestational weight gain, obstetric and neonatal outcomes: FitMum randomized controlled trial.

BACKGROUND: To investigate the effects of two different exercise interventions during pregnancy on gestational weight gain (GWG) and obstetric and neonatal outcomes compared to standard care. Additionally, we aimed to improve standardization of GWG measurements by developing a model to estimate GWG for a standardized pregnancy period of 40 weeks and 0 days accounting for individual differences in gestational age (GA) at delivery. METHODS: In a randomized controlled trial we compared the effects of structured supervised exercise training (EXE) three times per week throughout pregnancy versus motivational counselling on physical activity (MOT) seven times during pregnancy with standard care (CON) on GWG and obstetric and neonatal outcomes. Uniquely, to estimate GWG for a standardized pregnancy period, we developed a novel model to predict GWG based on longitudinally observed body weights during pregnancy and at admission for delivery. Observed weights were fitted to a mixed effects model that was used to predict maternal body weight and estimate GWG at different gestational ages. Obstetric and neonatal outcomes, among them gestational diabetes mellitus (GDM) and birth weight, were obtained after delivery. GWG and the investigated obstetric and neonatal outcomes are secondary outcomes of the randomized controlled trial, which might be underpowered to detect intervention effects on these outcomes. RESULTS: From 2018-2020, 219 healthy, inactive pregnant women with median pre-pregnancy BMI of 24.1 (21.8-28.7) kg/m2 were included at median GA 12.9 (9.4-13.9) weeks and randomized to EXE (n = 87), MOT (n = 87) or CON (n = 45). In total 178 (81%) completed the study. GWG at GA 40 weeks and 0 days did not differ between groups (CON: 14.9 kg [95% CI, 13.6;16.1]; EXE: 15.7 kg [14.7;16.7]; MOT: 15.0 kg [13.6;16.4], p = 0.538), neither did obstetric nor neonatal outcomes. For example, there were no differences between groups in the proportions of participants developing GDM (CON: 6%, EXE: 7%, MOT: 7%, p = 1.000) or in birth weight (CON: 3630 (3024-3899), EXE: 3768 (3410-4069), MOT: 3665 (3266-3880), p = 0.083). CONCLUSIONS: Neither structured supervised exercise training nor motivational counselling on physical activity during pregnancy affected GWG or obstetric and neonatal outcomes compared to standard care. TRIAL REGISTRATION: ClinicalTrials.gov; NCT03679130; 20/09/2018.

Cervical Osmotic Dilators versus Dinoprostone for Cervical Ripening during Labor Induction: A Systematic Review and Meta-analysis of 14 Controlled Trials.

OBJECTIVE: This study aimed to conduct a systematic review and meta-analysis of all randomized and nonrandomized controlled trials (RCTs and NCTs, respectively) that explored the maternal-neonatal outcomes of cervical osmotic dilators versus dinoprostone in promoting cervical ripening during labor induction. STUDY DESIGN: Six major databases were screened until August 27, 2022. The quality of included studies was evaluated. The data were summarized as mean difference or risk ratio (RR) with 95% confidence interval (CI) in a random-effects model. RESULTS: Overall, 14 studies with 15 arms were analyzed (n = 2,380 patients). Ten and four studies were RCTs and NCTs, respectively. The overall quality for RCTs varied (low risk n = 2, unclear risk n = 7, and high risk n = 1), whereas all NCTs had good quality (n = 4). For the primary endpoints, there was no significant difference between both groups regarding the rate of normal vaginal delivery (RR = 1.04, 95% CI: 0.95-1.14, p = 0.41) and rate of cesarean delivery (RR = 1.04, 95% CI: 0.93-1.17, p = 0.51). Additionally, there was no significant difference between both groups regarding the mean change in Bishop score and mean time from intervention to delivery. The rate of uterine hyperstimulation was significantly lower in the cervical osmotic dilator group. For the neonatal outcomes, during cervical ripening, the rate of fetal distress was significantly lower in the cervical osmotic dilator group. There was no significant difference between both groups regarding the mean Apgar scores, rate of meconium-stained amniotic fluid, rate of umbilical cord metabolic acidosis, rate of neonatal infection, and rate of neonatal intensive care unit admission. CONCLUSION: During labor induction, cervical ripening with cervical osmotic dilators and dinoprostone had comparable maternal-neonatal outcomes. Cervical osmotic dilators had low risk of uterine hyperstimulation compared with dinoprostone. Overall, cervical osmotic dilators might be more preferred over dinoprostone in view of their analogous cervical ripening effects, comparable maternal-neonatal outcomes, and lack of drug-related adverse events. KEY POINTS: · This is the first analysis of cervical osmotic dilators versus PGE2 for cervical ripening during labor.. · There was no difference between both arms regarding the rates of normal vaginal/cesarean deliveries.. · There was no difference between both arms regarding the rates of neonatal adverse events.. · Cervical osmotic dilators had significant lower risk of uterine hyperstimulation compared with PGE2.. · Cervical osmotic dilators may be superior to PGE2 in view of their similar efficacy and better safety..

Sulfation of hyperoside by the human cytosolic sulfotransferases (SULTs): impact of genetic polymorphisms on hyperoside-sulfating activity of SULT1C4 allozymes.

This study aimed to identify human cytosolic sulfotransferases (SULTs) that are capable of mediating hyperoside sulfation and examine the impact of genetic polymorphisms on their sulfating activity. Of the thirteen known human SULTs analyzed, five (1A1, 1A2, 1A3, 1C2, and 1C4) displayed sulfating activity toward hyperoside. Kinetic parameters of SULT1C4 that showed the strongest sulfating activity were determined. Ten SULT1C4 allozymes previously prepared were shown to display differential sulfating activities toward hyperoside, revealing clearly the functional impact of SULT1C4 genetic polymorphisms. These findings provided a robust biochemical foundation for further studies on the metabolism of hyperoside by sulfation.

Biogenic Preparation and Characterization of Silver Nanoparticles from Seed Kernel of Mangifera indica and Their Antibacterial Potential against Shigella spp.

Shigellosis is a serious foodborne diarrheal disease caused by the Shigella species. It is a critical global health issue. In developing countries, shigellosis causes most of the mortality in children below 5 years of age. Globally, around 165 million cases of diarrhea caused by Shigella are reported, which accounts for almost 1 million deaths, in which the majority are recorded in Third World nations. In this study, silver nanoparticles were synthesized using Mangifera indica kernel (MK-AgNPs) seed extracts. The biosynthesized M. indica silver nanoparticles (MK-AgNPs) were characterized using an array of spectroscopic and microscopic tools, such as UV-Vis, scanning electron microscopy, particle size analyzer, Fourier transform infrared spectroscopy, and X-ray diffractometer. The nanoparticles were spherical in shape and the average size was found to be 42.7 nm. The MK-AgNPs exhibited remarkable antibacterial activity against antibiotic-resistant clinical Shigella sp. The minimum inhibitory concentration (MIC) value of the MK-AgNPs was found to be 20 µg/mL against the multi-drug-resistant strain Shigella flexneri. The results clearly demonstrate that MK-AgNPs prepared using M. indica kernel seed extract exhibited significant bactericidal action against pathogenic Shigella species. The biosynthesized nanoparticles from mango kernel could possibly prove therapeutically useful and effective in combating the threat of shigellosis after careful investigation of its toxicity and in vivo efficacy.

Exploring the role of Islam on the lived experience of patients with Long QT Syndrome in Saudi Arabia.

Genetic services are rapidly growing in the Arab world leading to increasing number of patients being diagnosed with genetic disorders. Islam is the only/major religion of the local population in these countries. Muslim patients integrate religion in virtually every aspect of their lives, and it is vital to understand the role of Islam on their coping and decision-making in the context of genetic counseling. This will help provide patients with the most appropriate services aligned to their religious beliefs and will improve outcomes. Increasing numbers of patients are being diagnosed with Long QT syndrome in Saudi Arabia. Using semi-structured interviews, this study explored the role of Islam on the lived experience of 13 Saudi participants diagnosed with autosomal dominant Long QT syndrome (3/13) or who are carriers of Jervell and Lange-Nielsen syndrome (10/13). The interviews investigated how they made sense of living with the condition in light of their religion/spirituality. The data were analyzed using interpretative phenomenological analysis and produced four superordinate themes: 1) Common belief and idiosyncratic interpretation; 2) Using religion to justify positive reframing of current illnesses; 3) Interplay between belief in medicine and in religion; and 4) Complex impact of diagnosis on religiosity. The results show that the participants' idiosyncratic interpretations of the religious principles, not the principles themselves, had an important influence on their coping, medical decision-making, perceptions regarding the cause of their disease, and compliance with medical advice. A novel insight of the current study is that the personal understanding and interpretation of medical information played the greatest role in the decision-making process, and not the religious beliefs. Thus, it is important for health professionals to give patients' information in a manner that is clear and detailed in order for them to facilitate an informed decision, and to ensure that they fully understand the implications.

Economic optimization to guide climate water stress adaptation.

Allocation of water over its six dimensions of quantity, quality, timing, location, price, and cost remains an ongoing challenge facing water resource planning worldwide. This challenge is magnified with growing evidence of climate change and related water supply stressors. This stress will challenge food, energy, and water systems as climate adaptation policy measures see continued debate. Despite numerous achievements made many by previous works, few attempts have scanned the literature on economic optimization analysis for water resources planning to discover affordable climate adaptation measures. This paper aims to fill that gap by reviewing the literature on water resource optimization analysis at the basin scale to guide discovery of affordable climate adaptation measures. It does so by posing the question "What principles, practices, and recent developments are available to guide discovery of policy measures to improve water resource system adaptions to growing evidence of climate water stress?" It describes past achievements and identifies improvements needed for optimization analysis to inform policy debates for crafting plans to improve climate resilience. It describes an economic conceptual framework as well as identifying data needs for conducting economic optimization exercises to support river basin planning faced by the challenge of managing the six water dimensions described above. It presents an example from an ongoing issue facing water planners in the Middle East. Conclusions find considerable utility in the use of economic optimization exercises to guide climate water stressadaptation. Any use of trade, firm, or product names is for descriptive purposes only and does not imply endorsement by the U.S. Government.

Correction: Rubnawaz et al. Polyphenol Rich Ajuga bracteosa Transgenic Regenerants Display Better Pharmacological Potential. Molecules 2021, 26, 4874.

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Protective Effects of Green Tea Supplementation against Lead-Induced Neurotoxicity in Mice.

The use of natural products as therapeutic agents is rapidly growing recently. In the current study, we investigated the protective effects of green tea supplementation on lead-induced toxicity in mice. Forty albino mice were divided into four groups as follows: A: control group; B: green tea receiving group; C: lead-intoxicated group; and D: lead-intoxicated group supplemented with green tea. At the end of the experiment, the animals were tested for neurobehavioral and biochemical alterations. Green tea was analyzed through Gas Chromatography-Mass Spectrometry (GC/MS) analysis. We found that supplementation with green tea ameliorated the lead-associated increase in body weight and blood glucose. Green tea supplementation also changed the blood picture that was affected due to lead toxicity and ameliorated lead-induced dyslipidemia. The group of mice that were supplemented with green tea has shown positive alterations in locomotory, anxiety, memory, and learning behaviors. The GC/MS analysis revealed many active ingredients among which the two most abundant were caffeine and 1,2-benzenedicarboxylic acid, mono(2-ethylhexyl) ester. We concluded that green tea supplementation has several positive effects on the lead-induced neurotoxicity in mice and that these effects may be attributed to its main two active ingredients.

Sulfation of Quercitrin, Epicatechin and Rutin by Human Cytosolic Sulfotransferases (SULTs): Differential Effects of SULT Genetic Polymorphisms.

Radix Bupleuri is one of the most widely used herbal medicines in China for the treatment of fever, pain, and/or chronic inflammation. Quercitrin, epicatechin, and rutin, the flavonoids present in Radix Bupleuri, have been reported to display anti-inflammatory, antitumor, and antioxidant biological activities among others. Sulfation has been reported to play an important role in the metabolism of flavonoids. In this study, we aimed to systematically identify the human cytosolic sulfotransferase enzymes that are capable of catalyzing the sulfation of quercitrin, epicatechin, and rutin. Of the thirteen known human cytosolic sulfotransferases, three (cytosolic sulfotransferase 1A1, cytosolic sulfotransferase 1C2, and cytosolic sulfotransferase 1C4) displayed sulfating activity toward quercitrin, three (cytosolic sulfotransferase 1A1, cytosolic sulfotransferase 1A3, and cytosolic sulfotransferase 1C4) displayed sulfating activity toward epicatechin, and six (cytosolic sulfotransferase 1A1, cytosolic sulfotransferase 1A2, cytosolic sulfotransferase 1A3, cytosolic sulfotransferase 1B1, cytosolic sulfotransferase 1C4, and cytosolic sulfotransferase 1E1) displayed sulfating activity toward rutin. The kinetic parameters of the cytosolic sulfotransferases that showed the strongest sulfating activities were determined. To investigate the effects of genetic polymorphisms on the sulfation of quercitrin, epicatechin, and rutin, individual panels of cytosolic sulfotransferase allozymes previously prepared were analyzed and shown to display differential sulfating activities toward each of the three flavonoids. Taken together, these results provided a biochemical basis underlying the metabolism of quercitrin, epicatechin, and rutin through sulfation in humans.

Tubed Temporalis Fascia for Nasal Dorsal Contouring: A Novel Technique.

INTRODUCTION: Nasal dorsum irregularities may occur after nasal trauma or as a postrhinoplasty complication. Here, we present a novel technique using temporalis fascia (TF) grafting for primary and revision rhinoplasty to repair the nasal dorsum, hide nasal irregularities, and improve nasal contouring. METHODS: This prospective cohort study was conducted from January 2019 to June 2019 and evaluated nasal dorsal contouring using the TF in a tubed form. The outcome variables were patient satisfaction, dorsal irregularity, and contour definition. The predictor variable was the use of tubed TF for dorsal augmentation. Other associated variables were age, sex, indication for surgery, surgery type, and graft size. Patient satisfaction was evaluated using the Rhinoplasty Outcome Evaluation questionnaire. A rhinoplasty specialist other than the surgeon who performed the procedure evaluated the dorsal augmentation outcomes by inspection and palpation of the dorsum. All statistical analyses were performed using the SPSS software. RESULTS: Seventy-four patients (21.6% men and 78.4% women) were treated with the tubed TF. The mean age was 28.97 years. Thin skin was the most common indication (48.6%) for using TF. The graft size was 2-5 cm; inspection and palpation revealed no irregularities. No reception site complications occurred. One patient had a mild hematoma at the donor site. The mean patient satisfaction score was 10.14 preoperatively and 19.95 postoperatively (p = 0.001). DISCUSSION/CONCLUSIONS: Our novel technique of using the TF graft in a tubed form was easy to perform. Furthermore, the tubed TF covers all irregularities, is good for dorsal augmentation, and improves dorsal contouring and definition.