Osteometabolic profile and bone mass in the transition phase: ethnic differences in Brazilians treated with somatropin during childhood

Abstract Objective: The main growth hormone action is to promote linear growth increasing protein synthesis stimulation and osteoblastic activity. Peak bone mass extends from adolescence to 30 years of age. Several factors may influence this acquisition and prevent fracture risk in adulthood, such as genetic potential, GH, ethnicity, and lifestyle factors. This study aims to compare bone mass and osteometabolic profile of white and Afro-descendant Brazilian adolescents in the transition phase, who were treated with human recombinant growth hormone in childhood. Methods: The authors selected 38 adolescents from the Transition Outpatient Clinic of the University of São Paulo. Lumbar spine and total body bone mineral density (BMD) and bone mineral content (BMC), serum calcium, 25-OH-vitamin D and bone markers were analyzed at the rhGH withdrawal. Results: The mean age was 16.8 ± 1.6 years. There were 21 Afro-descendant and 17 whites. Thirty-four percent of the sample presented vitamin D insufficiency, 66% inadequate calcium intake and 44.7% physical inactivity. The Afro-descendants showed a lower lumbar spine and total body Z scores than those of the whites (p = 0.04 and p = 0.03, respectively), as well as their mean body weight (p = 0.03). There were no differences in the remaining osteometabolic parameters. Conclusion: As most adolescents had vitamin D insufficiency, low calcium intake, and physical inactivity, calcium, and cholecalciferol supplementation and lifestyle changes should be encouraged. The Brazilian Afro-descendant may be a vulnerable group for low bone mass, requiring

Actively separated microneedle patch for sustained-release of growth hormone to treat growth hormone deficiency

Growth hormone deficiency (GHD) has become a serious healthcare burden, and presents a huge impact on the physical and mental health of patients. Here, we developed an actively separated microneedle patch (PAA/NaHCO3-Silk MN) based on silk protein for sustained release of recombinant human growth hormone (rhGH). Silk protein, as a friendly carrier material for proteins, could be constructed in mild full-water conditions and ensure the activity of rhGH. After manually pressing PAA/NaHCO3-Silk MN patch to skin for 1 min, active separation is achieved by absorbing the interstitial fluid (ISF) to trigger HCO3 ‒ in the active backing layer to produce carbon dioxide gas (CO2). In rats, the MN patch could maintain the sustained release of rhGH for more than 7 days, and produce similar effects as daily subcutaneous (S.C.) injections of rhGH in promoting height and weight with well tolerated. Moreover, the PAA/NaHCO3-Silk MN patch with the potential of painless self-administration, does not require cold chain transportation and storage possess great economic benefits. Overall, the PAA/NaHCO3-Silk MN patch can significantly improve patient compliance and increase the availability of drugs, meet current unmet clinical needs, improve clinical treatment effects of GHD patients.

The state of Sergipe contribution to GH research: from Souza Leite to Itabaianinha syndrome

ABSTRACT In the late 19th century, José Dantas de Souza Leite, a physician born in Sergipe, published the first detailed clinical description of acromegaly under the guidance of the French neurologist Pierre Marie. In 2014, the Brazilian Society of Endocrinology and Metabolism created the "José Dantas de Souza Leite Award", which is granted every two years to a Brazilian researcher who has contributed to the development of endocrinology. In 2022, the award was given to another physician from Sergipe, Manuel Hermínio de Aguiar Oliveira, from the Federal University of Sergipe for the description of "Itabaianinha syndrome" in a cohort of individuals with isolated GH deficiency due to a homozygous inactivating mutation in the GH-releasing hormone receptor gene. This research, which was carried out over almost 30 years, was performed in partnership with Roberto Salvatori from Johns Hopkins University and in collaboration with other researchers around the world. This review article tells the story of Souza Leite, some milestones in the history of GH, and summarizes the description of Itabaianinha syndrome.

Expression and characterization of a bifunctional thermal β-glucosidase IuBgl3 from thermophilic archaeon Infirmifilum uzonense / 生物工程学报

β-glucosidase has important applications in food, medicine, biomass conversion and other fields. Therefore, exploring β-glucosidase with strong stability and excellent properties is a research hotspot. In this study, a GH3 family β-glucosidase gene named Iubgl3 was successfully cloned from Infirmifilum uzonense. Sequence analysis showed that the full length of Iubgl3 was 2 106 bp, encoding 702 amino acids, with a theoretical molecular weight of 77.0 kDa. The gene was cloned and expressed in E. coli and the enzymatic properties of purified IuBgl3 were studied. The results showed that the optimal pH and temperature for pNPG hydrolysis were 5.0 and 85 ℃, respectively. The enzyme has good thermal stability, and more than 85% of enzyme activity can be retained after being treated at 80 ℃ for2 h. This enzyme has good pH stability and more than 85% of its activity can be retained after being treated at pH 4.0-11.0 for 1 h. It was found that the enzyme had high hydrolysis ability to p-nitrophenyl β-d-glucoside (pNPG) and p-nitrophenyl β-d-xylopyranoside (pNPX). When pNPG was used as the substrate, the kinetic parameters Km and Vmax were 0.38 mmol and 248.55 μmol/(mg·min), respectively, and the catalytic efficiency kcat/Km was 6 149.20 s-1mmol-1. Most metal ions had no significant effect on the enzyme activity of IuBgl3. SDS completely inactivated the enzyme, while EDTA increased the enzyme activity by 30%. This study expanded the β-glucosidase gene diversity of the thermophilic archaea GH3 family and obtained a thermostable acid bifunctional enzyme with good industrial application potential.

Clinical characteristics of pituitary GH adenomas patients with different responses to oral glucose inhibitory GH test / 中华内分泌代谢杂志

Objective:To analyzed clinical characteristics of pituitary growth hormone(GH) adenomas patients with different responses to oral glucose inhibitory GH test.Methods:The clinical data of 50 patients with pituitary GH adenomas newly diagnosed with complete test data and case data in the Department of Endocrinology of Chinese PLA General Hospital was retrospectively analyzed from 2016 to 2021. The cases were divided into two groups according to the cutoff point of GH elevating to 50% of basaline during oral glucose test: abnormal elevation group(A group, n=16) and non-elevation group(B group, n=34). The clinical features, biochemistry, iconography, and immunohistochemistry of the two groups were analyzed. Results:The serum total cholesterol(TC)[(3.9±0.8) vs (4.6±0.9)mmol/L], 120 minutes insulin after glucose loading [11.2(4.4, 25.0) vs 92.0(10.8, 311.8)mU/L], long [1.0(0.4, 2.1) vs 1.5(0.5, 7.3) cm] and short[0.6(0.3, 1.3) vs 1.0(0.5, 5.8)cm] diameters of adenomas in A group were less than those in B group(all P<0.05) while insulin-like growth factor Ⅰ(IGF-Ⅰ) level was higher [(908.2±233.7) vs (743.1±273.1) ng/mL, P<0.05]. There were no significant differences in sex, age, disease course, clinical features, random GH, homeostasis model assessment of insulin resistance index(HOMA-IR), pituitary adenoma site, and invasive properties between the two groups. The immunohistochemical positive rates of ACTH(33% vs 0%) and prolactin(100% vs 28.6%)in A group were higher than those in B group( P<0.05). Conclusion:Pituitary GH adenomas patients with a paradoxical GH response pattern display lower serum TC and 120 minutes insulin levels as well as higher IGF-Ⅰ concentration and proportion of pituitary microadenomas. " Pure" growth hormone tumors may represent entities of a particular class of diseases in acromegaly.

Management of hypopituitarism: a perspective from the Brazilian Society of Endocrinology and Metabolism

ABSTRACT Hypopituitarism is a disorder characterized by insufficient secretion of one or more pituitary hormones. New etiologies of hypopituitarism have been recently described, including head trauma, cerebral hemorrhage, and drug-induced hypophysitis. The investigation of patients with these new disorders, in addition to advances in diagnosis and treatment of hypopituitarism, has increased the prevalence of this condition. Pituitary hormone deficiencies can induce significant clinical changes with consequent increased morbidity and mortality rates, while hormone replacement based on current guidelines protects these patients. In this review, we will first discuss the different etiologies of hypopituitarism and then address one by one the clinical aspects, diagnostic evaluation, and therapeutic options for deficiencies of TSH, ACTH, gonadotropin, and GH. Finally, we will detail the hormonal interactions that occur during replacement of pituitary hormones.

miRNA-mediated regulation of auxin signaling pathway during plant development and stress responses

Auxin is one of the most important plant growth hormones, playing a crucial role in development as well as instress responses. Auxin biosynthesis and signaling pathway comprises a series of events including auxinperception by the receptor, activation, and function of auxin response factors and control by auxin repressors.All these factors are regulated by several different microRNAs during leaf, flower and fruit development,anther development, nodulation, lateral and adventitious root development, potato tuber development as wellas during heat stress, submergence, boron toxicity, aluminium stress responses, etc., as depicted in the availableliterature. In this review a thorough study on miRNA-mediated regulation of auxin biosynthesis and signalinghas been done in various plant species. The data gathered can be utilized to point out the particular miRNAmediated regulation module which can be utilized to modulate the expression of the miRNA and therebymodulation of the auxin pathway. Information in this review would be beneficial to utilize the miRNAexpression to generate the protocol for engineering plants with altered auxin signaling pathway to obtain betteryield and improved stress tolerance.

Thyroid gland changes in patients with acromegaly

ABSTRACT Objective Acromegaly is characterized by high neoplastic morbidity as a side effect of growth hormone (GH) hypersecretion. Increased incidence of goiter, thyroid carcinoma, and thyroid dysfunction is also reported. The aim of the present study was to find the prevalence of thyroid dysfunction and goiter in patients with acromegaly and determine its relationship to disease activity, disease duration, and the presence of secondary hypothyroidism. Subjects and methods In a cross-sectional study of the period 2008-2012 were included 146 patients with acromegaly (56 men, 90 women) of mean age 50.3 ± 12.4 years. Acromegaly disease activity and thyroid function were evaluated in all patients. Thyroid ultrasonography was performed to calculate thyroid volume and detect the presence of nodular goiter. Results Ninety-one patients were determined to have an active disease, and 55, a controlled disease. The mean thyroid volume in patients without previous thyroid surgery was 37.6 ± 38.8 mL. According to disease activity, thyroid volume was significantly higher in patients with active disease (38.5 ± 45.4 mL vs. 27.2 ± 18.4 mL, p = 0.036). A weak positive correlation was found between thyroid volume and insulin-like growth factor 1 (IGF-1) in the whole group and in females (R = 0.218; p = 0.013, and R = 0.238; p = 0.037, respectively). There was no significant correlation of thyroid volume with disease duration and GH level in the whole group and in both sexes. The patients with secondary hypothyroidism had twofold smaller thyroid volume, relative to the rest of the group. The prevalence of thyroid dysfunction was 39%, with a female to male percentage ratio of 1.73. Goiter was diagnosed in 87% of patients, including diffuse goiter (17.1%) and nodular (69.9%), with no significant difference between patients with active and controlled disease or the presence of secondary hypothyroidism. Conclusions Thyroid volume in patients with acromegaly depends on disease activity and the presence of secondary hypothyroidism as a complication. The increased prevalence of nodular goiter determines the need of regular ultrasound thyroid evaluation in the follow-up of patients with acromegaly. Arch Endocrinol Metab. 2020;64(3):269-75

Maltol total alkaloid inhibits expression and secretion of prolactin by upregulating dopamine D2 receptor / 中草药

Objective: To study the role of dopamine D2 receptor (D2R) on the regulation of prolactin (PRL) secretion by malt total alkaloids. Methods: MMQ and GH3 cells of pituitary adenoma were divided into control group, bromocriptine (5 μg/mL), malt total alkaloids (4.4, 8.8, 35.2, 70.4 μg/mL), haloperidol (10, 20, 40 μg/mL), and combined administration group of total malt alkaloids and haloperidol. Cell viability was detected by CCK-8; The expressions of PRL and D2R were detected by western blotting; The level of PRL was detected by ELISA; The level of PRL and D2R mRNA were detected by qRT-PCR. Results: Compared with control group, malt alkaloids (35.2, 70.4 μg/mL) significantly reduced the expression levels of PRL protein and mRNA, and the level of PRL in the supernatant of MMQ cells (P < 0.05). Malt alkaloids (35.2, 70.4 μg/mL) significantly increased the expression levels of D2R protein and mRNA in MMQ cells. Haloperidol significantly inhibited the downregulation of malt alkaloids on the expression levels of PRL protein and mRNA, and the expression level of PRL in supernatant of MMQ cells (P < 0.05). Haloperidol significantly inhibited the upregulation of malt alkaloids on the levels of D2R protein and mRNA (P < 0.05). The level of PRL in GH3 cells had no change by malt alkaloids. Conclusion: Malt alkaloids could inhibit the expression and secretion of PRL in MMQ cell by upregulating D2R.

Insulin signaling in the whole spectrum of GH deficiency

ABSTRACT GH is one of the insulin counterregulatory hormones which acts in the opposite way to insulin, increasing the glucose production by the liver and kidneys and decreasing glucose uptake from peripheral tissues, thus being a hyperglycemic hormone. When in excess, as in acromegaly, it induces glucose intolerance and diabetes. As expected, patients with GH deficiency (GHD) have hypoglycemia, especially in early childhood, but as GH is also a lipolytic hormone, these patients are becoming obese with higher percentages of body fat. Although obesity in general is directly related to insulin resistance, in patients with GH secretion disorders this relationship may be altered. In acromegaly there is a decrease in fat mass with worsening insulin sensitivity and mice with isolated GHD are characterized by greater insulin sensitivity despite excess fat mass. In humans with GHD, body composition shows increased body fat and decreased free fat mass, but the results regarding insulin sensitivity are still controversial in these patients. These discrepant results regarding insulin sensitivity in patients with GHD suggest the existence of other variables influencing these results. In the present review, we will try to follow the path of the different researches conducted on this subject, both in animal and human models, with the goal of understanding the current knowledge of insulin sensitivity across the spectrum of GHD. Arch Endocrinol Metab. 2019;63(6):582-91

Effects of growth hormone in the central nervous system

ABSTRACT Growth hormone (GH) is best known for its effect stimulating tissue and somatic growth through the regulation of cell division, regeneration and proliferation. However, GH-responsive neurons are spread over the entire central nervous system, suggesting that they have important roles in the brain. The objective of the present review is to summarize and discuss the potential physiological importance of GH action in the central nervous system. We provide evidence that GH signaling in the brain regulates the physiology of numerous functions such as cognition, behavior, neuroendocrine changes and metabolism. Data obtained from experimental animal models have shown that disruptions in GH signaling in specific neuronal populations can affect the reproductive axis and impair food intake during glucoprivic conditions, neuroendocrine adaptions during food restriction, and counter-regulatory responses to hypoglycemia, and they can modify gestational metabolic adaptions. Therefore, the brain is an important target tissue of GH, and changes in GH action in the central nervous system can explain some dysfunctions presented by individuals with excessive or deficient GH secretion. Furthermore, GH acts in specific neuronal populations during situations of metabolic stress to promote appropriate physiological adjustments that restore homeostasis. Arch Endocrinol Metab. 2019;63(6):549-56

Purification and biochemical characterization of a novel thermophilic exo-ß-1, 3-glucanase from the thermophile biomass-degrading fungus Thielavia terrestris Co3Bag1

Background: The aim of this work was to purify and characterize exo-ß-1,3-glucanase, namely, TtBgnA, from the thermophilic fungus Thielavia terrestris Co3Bag1 and to identify the purified enzyme. Results: The thermophilic biomass-degrading fungus T. terrestris Co3Bag1 displayed ß-1,3-glucanase activity when grown on 1% glucose. An exo-ß-1,3-glucanase, with an estimated molecular mass of 129 kDa, named TtBgnA, was purified from culture filtrates from T. terrestris Co3Bag1. The enzyme exhibited optimum activity at pH 6.0 and 70°C and half-lives (t1/2) of 54 and 37 min at 50 and 60°C, respectively. Substrate specificity analysis showed that laminarin was the best substrate studied for TtBgnA. When laminarin was used as the substrate, the apparent KM and Vmax values were determined to be 2.2 mg mL-1 and 10.8 U/mg, respectively. Analysis of hydrolysis products by thin-layer chromatography (TLC) revealed that TtBgnA displays an exo mode of action. Additionally, the enzyme was partially sequenced by tandem mass spectrometry (MS/MS), and the results suggested that TtBgnA from T. terrestris Co3Bag1 could be classified as a member of the GH-31 family. Conclusions: This report thus describes the purification and characterization of TtBgnA, a novel exo-ß-1,3-glucanase of the GH-31 family from the thermophilic fungus T. terrestris Co3Bag1. Based on the biochemical properties displayed by TtBgnA, the enzyme could be considered as a candidate for potential biotechnological applications.

Pegvisomant in acromegaly: a multicenter real-life study in Argentina

ABSTRACT Objective To describe the long term safety and efficacy of pegvisomant (PEGV), and the predictors of treatment response in patients with acromegaly in the real life setting. Subjects and methods We retrospectively reviewed the clinical, hormonal and radiological data of acromegalic patients treated with PEGV in 17 Argentine centers. Results Seventy-five patients (age range 22-77, 51 females) with acromegaly have been treated with PEGV for up to 118 months (median 27 months). Before PEGV, 97.3% of patients had been treated with medical therapy, surgery and/or radiotherapy, two patients had no previous treatment. At that time, all patients had an IGF-1 above the upper normal limit (ULN) (mean 2.4 x ULN ± 0.98, range 1.25-7). At diagnosis of acromegaly 84% presented macroadenomas, prior to PEGV only 23,5% of patients remained with tumor remnant > 1 cm, the remaining showed normal or less than 1 cm images. Disease control (IGF-1 ≤ 1.2 x ULN) was achieved in 62.9% of patients with a mean dose of 11.8 mg/day. Thirty-four patients (45%) received PEGV monotherapy, while 41 (55%) received combined therapy with either somatostatin analogues and/or cabergoline. Adverse events related to PEGV were: local injection site reaction in 5.3%, elevated liver enzymes in 9.3%, and tumor size growth in 9.8%. Pre-PEGV IGF-I level was the only predictor of treatment response: 2.1 x ULN vs 2.8 x ULN in controlled and uncontrolled patients respectively (p < 0.001). Conclusion this long term experience indicates PEGV treatment was highly effective and safe in our series of Argentine patients with acromegaly refractory to standard therapies. Arch Endocrinol Metab. 2019;63(4):320-7

Velocidad de crecimiento en pacientes con síndrome de Turner que recibieron hormona recombinante de crecimiento / Growth rate in patients with Turner syndrome who received recombinant growth hormone

El síndrome de Turner (ST) afecta a uno de cada 2000-2500 recién nacidos vivos y tiene una prevalencia de 50 por cada 100 000 mujeres. Las manifestaciones clínicas son variables, dependiendo del tipo de alteración cromosómica y de la edad de presentación. Una de las características más prevalentes y sobresalientes del síndrome es su estatura extremadamente baja. La hormona de crecimiento humana recombinante (rh-GH) se ha usado para aumentar el crecimiento y la estatura final en las niñas que tienen el síndrome de Turner. Para valorar los efectos de la hormona de crecimiento recombinante en las niñas y adolescentes con ST, hemos tomado en cuenta el efecto de la hGH, considerando la velocidad en la talla de crecimiento como un punto importante del estudio observacional retrospectivo. Resultados principales: El uso de rh-GH tiene una relación estadísticamente significativa (p0.049 <0.05), que se asocia con un factor de influencia positiva en relación con la velocidad de crecimiento, como variable principal. Al comparar a las pacientes que recibieron la hormona de crecimiento con las que no la recibieron, en las primeras existe la tendencia a acercarse a la curva del percentil 10 en comparación con la de aquellas que no recibieron la rh-GH, que estuvieron más lejos de la curva.

Turner syndrome (TS) affects about one in 1500 to 2500 live-born females. One of the most prevalent and salient features of the syndrome is extremely short stature. Recombinant human growth hormone (rh-GH) has been used to increase growth and final height in girls who have Turner syndrome. To assess the effects of recombinant growth hormone in children and adolescents with TS we have evaluated the effect of HGH considering growth rate as an important point through a retrospective observational study. Main results: The use of rh-GH has a statistically significant relationship (p0.049 <0.05) that is associated with an influencing factor in favor of the use of rh-GH in relation to the variable growth rate. When comparing the patients who received growth hormone with those who did not receive, there is the tendency to arrive closer to the 10th percentile curve compared to the curve of the patients who did not receive rh-GH, which is further away.

Uso do hormônio do crescimento associado à fibrina rica em plaquetas e leucócitos injetável (I-PRF) / Use of the growth hormone associated with injectable platelet-rich fibrin (I-PRF)

Objetivo: demonstrar, por meio de uma revisão de literatura, a utilização do hormônio do crescimento (GH) e concentrados plaquetários e sugerir técnica de associação de uso para odontologia em processos de preservação de osso alveolar. Revisão de literatura: enxertos ósseos são uma necessidade na área da saúde, por diversas razões. A utilização de osso autógeno apresenta grande desvantagem em ter um segundo sítio cirúrgico, entretanto, os substitutos ósseos não possuem as características ideais. Assim, existe a busca por alternativas que otimizem a cicatrização e a incorporação dos substitutos ósseos, dentre elas os concentrados sanguíneos, ricos em fatores de crescimento derivados das plaquetas e o hormônio do crescimento. É possível encontrar uma vasta literatura utilizando os concentrados sanguíneos, inclusive utilizando esses como veículos para outras substâncias. Os concentrados sanguíneos são ricos em fatores de crescimento derivados das plaquetas, como fator de crescimento semelhante à insulina (IGF), Fator de crescimento derivado de plaquetas (PDGF) e outros. Além disso, também é possível encontrar, na literatura, o uso tópico de hormônio do crescimento em enxertos ósseos, fraturas e implantes dentários. Entretanto, o GH possui uma meia-vida de 20 minutos, assim, quando utilizado em conjunto com a I-PRF, espera-se um aumento no tempo de ação local. Considerações finais: é possível otimizar os enxertos ósseos utilizando-se L-PRF/I-PRF e hormônio do crescimento. Porém, são necessárias mais pesquisas.(AU)

Objective: this study aims to show through a literature review the use of the growth hormone and platelet concentrates and to suggest an association technique for dentistry use in alveolar bone preservation processes. Literature review: bone grafts are a health requirement for a number of reasons. The use of autogenous bone has the main disadvantage of a second surgical site, while bone substitutes do not present optimal characteristics. Thus, there is a search for alternatives that optimize the healing and incorporation of bone substitutes, which include blood concentrates that are rich in platelet-derived growth factors and the growth hormone. A vast literature can be found on blood concentrates, including their use as vehicles to other substances. Blood concentrates are rich in platelet-derived growth factors such as IGF, PDGF, and others. Moreover, the literature also shows the topical use of the growth hormone in bone grafts, fractures, and dental implants. However, the growth hormone presents a half-life of 20 minutes; therefore, when combined with I-PRF, an increased time in local action is expected. Final considerations: it is possible to optimize bone grafts by using L-PRF/I-PRF and the growth hormone. However, further research is required.(AU)

The sleeping giant: An atypical case of a giant Pituitary Adenoma presenting as Acromegaly with minimal symptoms of mass effect / Journal of the ASEAN Federation of Endocrine Societies

Introduction@#This is a case of patient with giant pituitary adenoma (GPA) presenting with acromegalic features, minimal symptoms of mass effect who underwent surgical resection via transcranial approach with minimal surgical morbidity.@*Case@#A 40-year-old female presented with typical acromegalic features over 14 years, occasional mild frontal headaches and blurred vision. She had elevated growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Cranial MRI revealed a 6.4x7x5.5 cm lobulated pituitary mass with cystic degeneration, areas of necrosis with mass effect on several intracranial structures. Excision via craniotomy reduced mass size to 5.9x5.8x4.7 cm. Histopathology revealed a mixed GH- and prolactin-secreting pituitary adenoma. She was maintained on bromocriptine and underwent radiotherapy. Repeat IGF-1 levels remained elevated but symptoms did not progress@*Conclusion@#This is a case of a patient with GPA with minimal symptom of mass effect, with no hormonal improvement post-surgery and radiotherapy. Ideally, a multi-staged surgery can be done with optimization of medical management. In the absence of these medications locally and reluctance of patient for re-surgery, the team opted to monitor tumor size, hormone levels and maximize management of co-morbidities.

Network pharmacology of Chaihu Shugan Powder for treating post-stroke depression / 中草药

Objective: To assess the effective components of Chaihu Shugan Powder in the treatment of post-stroke depression and its potential mechanisms. Methods: The chemical constituents and targets of Chaihu Shugan Powder were obtained from Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Common targets for stroke and depression were obtained from OMIM, TTD, and PharmGkb databases. Excel was used to filter molecules and targets, so as the Cytoscape software to establish the network between Chinese medicine molecules and target. The biological information annotation database was used to analyze gene function and metabolic pathway. Results: There were 122 Chinese medicine ingredients from databases mteracting with 42 target proteins of post-stroke depression. Finally, five targets including Estrogen receptor (ESR1), prostaglandin G/H synthase 2 (PTGS2), glycogen synthase kinase-3 beta (GSK3β), sodium-dependent dopamine transporter (SLC6A4), and leukotriene A-4 hydrolase (LTA4H) were selected as the action targets for treating post-stroke depression, involved the arachidonic acid metabolism, 5-serotonin ergic synaptic pathway, prolactin signaling pathway, and thyroid hormone signaling pathways, which can treat post-stroke depression by regulating inflammatory response, synapse synthesis, estrogen response, recollection, biosynthesis, drug reaction, and circadian rhythm.Conclusion: The network pharmacology study revealed the underlying mechanisms of Chaihu Shugan Powder for treating the post-stroke depression.

Isolation and characterization of a novel endo-beta-1, 4-glucanase from a metagenomic library of the black-goat rumen

ABSTRACT The various types of lignocellulosic biomass found in plants comprise the most abundant renewable bioresources on Earth. In this study, the ruminal microbial ecosystem of black goats was explored because of their strong ability to digest lignocellulosic forage. A metagenomic fosmid library containing 115,200 clones was prepared from the black-goat rumen and screened for a novel cellulolytic enzyme. The KG35 gene, containing a novel glycosyl hydrolase family 5 cellulase domain, was isolated and functionally characterized. The novel glycosyl hydrolase family 5 cellulase gene is composed of a 963-bp open reading frame encoding a protein of 320 amino acid residues (35.1 kDa). The deduced amino acid sequence showed the highest sequence identity (58%) for sequences from the glycosyl hydrolase family 5 cellulases. The novel glycosyl hydrolase family 5 cellulase gene was overexpressed in Escherichia coli. Substrate specificity analysis revealed that this recombinant glycosyl hydrolase family 5 cellulase functions as an endo-β-1,4-glucanase. The recombinant KG35 endo-β-1,4-glucanase showed optimal activity within the range of 30-50 °C at a pH of 6-7. The thermostability was retained and the pH was stable in the range of 30-50 °C at a pH of 5-7.

Long-term follow-up of patients with elevated IGF-1 and nadir GH > 0 4 µg/L but < 1 µg/L

ABSTRACT Objective To report the results of initial investigation and after 5 years of patients with a suspicious clinical scenario for acromegaly, elevated IGF-1, and nadir GH during an oral glucose tolerance test (OGTT) > 0.4 µg/L but < 1 µg/L. Subjects and methods Seventeen patients who had elevated IGF-1 (outside puberty and pregnancy) in two measurements and GH between 0.4 and 1 µg/L during OGTT were selected. Results During initial assessment, only one patient had microadenoma on magnetic resonance imaging (MRI) of the pituitary. In this patient, IGF-1 returned to normal spontaneously after 5 years. In the remaining 16 patients, spontaneous normalization of IGF-1 was observed in four and IGF-1 continued to be elevated in 12 after 5 years. None of the latter patients developed a phenotype of acromegaly, changes in physiognomy or increase in IGF-1 and no tumor was detected by imaging methods. Two patients had nadir GH < 0.4 µg/L, while the nadir GH remained between 0.4 and 1 µg/L in 10 patients. Conclusion In patients (notably young adult or adult women) without a typical phenotype in whom IGF-1 is measured due to a suspicious clinical scenario and is found to be slightly elevated, even if confirmed and in the absence of other causes, a nadir GH cut-off value of 0.4 µg/L instead of 1 µg/L in the OGTT might be inadequate for the diagnosis.

Eje somatotrópico y marcadores moleculares del metabolismo mineral en niños en diálisis / Somatotropic axis and molecular markers of mineral metabolism in children undergoing chronic peritoneal dialysis

El retraso del crecimiento de los niños con enfermedad renal crónica es de origen multifactorial, incluyendo la resistencia a hormona de crecimiento (GH) y alteraciones en el metabolismo mineral óseo. Objetivos: 1) Caracterizar marcadores del metabolismo mineral: FGF23-Klotho y del eje somatotrópico: IGF1, IGFBP3 y GHBP, en niños en diálisis peritoneal (DP); 2) Evaluar la evolución de la talla en aquellos pacientes tratados con rhGH. Pacientes y Método: Niños prepuberales en DP seguidos durante 12 meses. Criterios exclusión fueron Tanner > 1, síndrome nefrótico activo, tratamiento esteroidal, malabsorción gastrointestinal, enfermedades endocrinas, síndromes genéticos, uso de rhGH al ingreso del estudio. Se evaluaron variables demográficas, antropométricas: Z talla/edad, (ZT/E), velocidad de crecimiento (VC), bioquímicas (calcio, fósforo, PTH), marcadores del metabolismo mineral (25OHvitD, 1,25OHvitD, FGF23, Klotho), y de crecimiento (IGF-1, IGFBP-3, GHBP). Resultados: Quince pacientes, 7 varones, edad 6,9 ± 3,0 años, tiempo en DP 14,33 ± 12,26 meses. Puntaje ZT/E al mes 1= -1,69 ± 1,03. FGF23: 131,7 ± 279,4 y Klotho: 125,9 ± 24,2 pg/ml. Durante los 12 meses de seguimiento no hubo diferencia significativa en el promedio de las variables. El uso de rhGH en 8 pacientes no mostró mejoría significativa del ZT/E ni la VC. El análisis bivariado mostró correlación positiva entre niveles de Klotho y delta ZT/E, y entre GHBP y VC (p < 0,05). Conclusiones: Los valores de FGF23 se encuentran elevados y los de Klotho disminuidos en niños con enfermedad renal crónica en DP en comparación con niños sanos. Las variables de eje somatotrópico, se encuentran normales o elevadas. rhGH tiende a mejorar la talla y GHBP se correlaciona positivamente con VC en estos niños.

Growth failure is one of the most relevant complications in children with chronic kidney disease (CKD). Among others, growth hormone (GH) resistance and bone mineral disorders have been identified as the most important causes of growth retardation. Objectives: 1. To characterize bone mineral metabolism and growth hormone bio-markers in CKD children treated with chronic peritoneal dialysis (PD). 2. To evaluate height change with rhGH treatment. Patients and Method: A longitudinal 12-month follow-up in prepuberal PD children. Exclusion criteria: Tanner stage >1, nephrotic syndrome, genetic disorders, steroids, intestinal absorption disorders, endocrine disturbances, treatment with GH to the entry of the study. Demographic and anthropometric data were registered. FGF23, Klotho, VitD, IGF-1, IGFBP3, and GHBP were measured to evaluate mineral and growth metabolism. Results: 15 patients, 7 male, age 6.9 ± 3.0 y were included. Time on PD was 14.33 ± 12.26 months. Height/age Z score at month 1 was -1.69 ± 1.03. FGF23 and Klotho: 131.7 ± 279.4 y 125.9 ± 24.2 pg/ml, respectively. 8 patients were treated with GH during 6-12 months, showing a non-significant increase in height/age Z-score during the treatment period. Bivariate analysis showed a positive correlation between Klotho and delta ZT/E, and between GHBP vs growth velocity index (p < .05). Conclusions: FGF23 values were high and Klotho values were reduced in children with CKD in PD, comparing to healthy children. Somatotropic axis variables were normal or elevated. rhGH tends to improve height and there is a positive correlation of GHBP and growth velocity in these children.