scholarly journals Restructuring of amygdala subregion apportion across adolescence

2019 ◽  
Author(s):  
Claire E. Campbell ◽  
Adam F. Mezher ◽  
Sandrah P. Eckel ◽  
J. Michael Tyszka ◽  
Wolfgang M. Pauli ◽  
...  
Keyword(s):  
Relative Proportion ◽  
Central Nucleus ◽  
Future Research ◽  
Developmental Patterns ◽  
Transition Area ◽  
Generalized Additive Mixed Models ◽  
Additive Mixed Models ◽  
Postmortem Studies ◽  
Relative Differences

AbstractTotal amygdala volumes develop in association with sex and puberty, and postmortem studies find neuronal numbers increase in a nuclei specific fashion across development. Thus, amygdala subregions and composition may evolve with age. Our goal was to examine if amygdala subregion absolute volumes and/or relative proportion varies as a function of age, sex, or puberty in a large sample of typically developing adolescents (N=408, 43% female, 10-17 years). Utilizing the in vivo CIT168 atlas, we quantified 9 subregions and implemented Generalized Additive Mixed Models to capture potential non-linear associations with age and pubertal status between sexes. Only males showed significant age associations with the basolateral ventral and paralaminar subdivision (BLVPL), central nucleus (CEN), and amygdala transition area (ATA). Again, only males showed relative differences in the proportion of the BLVPL, CEN, ATA, along with lateral (LA) and amygdalostriatal transition area (ASTA), with age. Using a best-fit modeling approach, age, and not puberty, was found to drive these associations. The results suggest that amygdala subregions show unique developmental patterns with age in males across adolescence. Future research is warranted to determine if our findings may contribute to sex differences in mental health that emerge across adolescence.

Abnormal Structure of von Willebrand Factor in Myeloproliferative Syndrome Is Associated to Either Thrombotic or Bleeding Diathesis

1987 ◽  
Vol 58 (02) ◽  
pp. 753-757 ◽  
Author(s):  
M F López-Fernández ◽  
C López-Berges ◽  
R Martín ◽  
A Pardo ◽  
F J Ramos ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Proteinase Inhibitors ◽  
Relative Proportion ◽  
Variable Degree ◽  
Bleeding Diathesis ◽  
Myeloproliferative Syndrome ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryThe multimeric and subunit patterns of plasma von Willebrand factor (vWF) were analyzed in eight patients with myeloproliferative syndrome (MS) in order to investigate the possible existence of heterogeneity in the “in vivo” proteolytic cleavage of the protein, previously observed in this entity. Six patients lacked large vWF multimers, five of them having normal bleeding times (BT) and clinically documented episodes of thrombotic origin, whereas one patient had long BT and bleeding symptoms. Seven patients showed a relative increase in the 176 kDa subunit fragment while the 189 kDa polypeptide was increased in only one. In addition, another patient (and prior to any therapy) showed the presence of a new fragment of approximately 95 kDa which disappeared after Busulfan therapy. The collection of blood from these patients with proteinase inhibitors did not correct the abnormalities.The infusion of DDAVP to two patients with abnormal vWF was accompanied by: the appearance of larger vWF multimers which disappeared rapidly from plasma; an increase in the relative proportion of the satellite bands of each multimer and a further increase of the 176 kDa fragment. These data point to some heterogeneity in the vWF abnormality present in MS which may be related in part to a variable degree of proteolysis of vWF occurring “in vivo” rather than “in vitro”, and which may be associated to either a thrombotic or a bleeding diathesis. They also suggest that despite the presence of abnormal, already proteolyzed vWF, DDAVP-enhanced proteolysis occurs in MS to a similar extent to what is described in normal individuals.

Metabolism and Distribution of Novel Tumor Targeting Drugs In Vivo

2020 ◽  
Vol 21 (13) ◽  
pp. 996-1008
Author(s):  
Mengli Wang ◽  
Qiuzheng Du ◽  
Lihua Zuo ◽  
Peng Xue ◽  
Chao Lan ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Small Molecule ◽  
High Efficiency ◽  
Tumor Therapy ◽  
Research Progress ◽  
Future Research ◽  
Pharmacokinetic Parameters ◽  
Molecular Characteristics ◽  
Targeted Drugs

Background: As a new tumor therapy, targeted therapy is becoming a hot topic due to its high efficiency and low toxicity. Drug effects of targeted tumor drugs are closely related to pharmacokinetics, so it is important to understand their distribution and metabolism in vivo. Methods: A systematic review of the literature on the metabolism and distribution of targeted drugs over the past 20 years was conducted, and the pharmacokinetic parameters of approved targeted drugs were summarized in combination with the FDA's drug instructions. Targeting drugs are divided into two categories: small molecule inhibitors and monoclonal antibodies. Novel targeting drugs and their mechanisms of action, which have been developed in recent years, are summarized. The distribution and metabolic processes of each drug in the human body are reviewed. Results: In this review, we found that the distribution and metabolism of small molecule kinase inhibitors (TKI) and monoclonal antibodies (mAb) showed different characteristics based on the differences of action mechanism and molecular characteristics. TKI absorbed rapidly (Tmax ≈ 1-4 h) and distributed in large amounts (Vd > 100 L). It was mainly oxidized and reduced by cytochrome P450 CYP3A4. However, due to the large molecular diameter, mAb was distributed to tissues slowly, and the volume of distribution was usually very low (Vd < 10 L). It was mainly hydrolyzed and metabolized into peptides and amino acids by protease hydrolysis. In addition, some of the latest drugs are still in clinical trials, and the in vivo process still needs further study. Conclusion: According to the summary of the research progress of the existing targeting drugs, it is found that they have high specificity, but there are still deficiencies in drug resistance and safety. Therefore, the development of safer and more effective targeted drugs is the future research direction. Meanwhile, this study also provides a theoretical basis for clinical accurate drug delivery.

Within-Person Variability in First Impressions From Faces

Perception ◽  
2021 ◽  
pp. 030100662110197
Author(s):  
Taylor Gogan ◽  
Jennifer Beaudry ◽  
Julian Oldmeadow
Keyword(s):  
First Impressions ◽  
Future Research ◽  
Image Variability ◽  
Relative Differences

Perceptions of an individual can change dramatically across different images of their face. Questions remain as to whether some traits are more sensitive to image variability than others. To investigate this issue, we constructed a database of 340 naturalistic images consisting of 20 photos of 17 individuals. In this preregistered study, 95 participants rated all 340 images on one of three traits: trustworthiness, dominance, or attractiveness. Across images, participants’ trustworthiness ratings tended to vary more than dominance, which in turn varied more than attractiveness; however, the relative differences between traits depended on the identity in question. Importantly, despite the variability in ratings within identities, there were substantial differences between individuals, suggesting that these trait judgements are based to some degree on relatively invariant facial characteristics. We found greater between-identity variability for attractiveness judgements compared to trustworthiness and dominance. Future research should further investigate the extent to which each trait dimension is tied to the identity of the faces.

scholarly journals Effect of Processing on Fish Protein Antigenicity and Allergenicity

Foods ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 969
Author(s):  
Xingyi Jiang ◽  
Qinchun Rao
Keyword(s):  
Fish Species ◽  
Protein Denaturation ◽  
Ex Vivo ◽  
Protein Solubility ◽  
Future Research ◽  
Food Protein ◽  
In Vivo Evaluation ◽  
Fish Allergy

Fish allergy is a life-long food allergy whose prevalence is affected by many demographic factors. Currently, there is no cure for fish allergy, which can only be managed by strict avoidance of fish in the diet. According to the WHO/IUIS Allergen Nomenclature Sub-Committee, 12 fish proteins are recognized as allergens. Different processing (thermal and non-thermal) techniques are applied to fish and fishery products to reduce microorganisms, extend shelf life, and alter organoleptic/nutritional properties. In this concise review, the development of a consistent terminology for studying food protein immunogenicity, antigenicity, and allergenicity is proposed. It also summarizes that food processing may lead to a decrease, no change, or even increase in fish antigenicity and allergenicity due to the change of protein solubility, protein denaturation, and the modification of linear or conformational epitopes. Recent studies investigated the effect of processing on fish antigenicity/allergenicity and were mainly conducted on commonly consumed fish species and major fish allergens using in vitro methods. Future research areas such as novel fish species/allergens and ex vivo/in vivo evaluation methods would convey a comprehensive view of the relationship between processing and fish allergy.

scholarly journals The Genus Lagochilus (Lamiaceae): A Review of Its Diversity, Ethnobotany, Phytochemistry, and Pharmacology

Plants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 132
Author(s):  
Nilufar Z. Mamadalieva ◽  
Davlat Kh. Akramov ◽  
Ludger A. Wessjohann ◽  
Hidayat Hussain ◽  
Chunlin Long ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Chemical Constituents ◽  
Iridoid Glycosides ◽  
Herbal Medicines ◽  
Future Research ◽  
South Central ◽  
Pharmacological Studies ◽  
Central South

The genus Lagochilus (Lamiaceae) is native to Central, South-Central, and Eastern Asia. It comprises 44 species, which have been commonly used as herbal medicines for the treatments of various ailments for thousands of years, especially in Asian countries. This review aims to summarize the chemical constituents and pharmacological activities of species from the genus Lagochilus to unveil opportunities for future research. In addition, we provide some information about their traditional uses, botany, and diversity. More than 150 secondary metabolites have been reported from Lagochilus, including diterpenes, flavonoids, phenolic compounds, triterpenoids, iridoid glycosides, lignans, steroids, alkaloids, polysaccharides, volatile, non-volatile and aromatic compounds, lipids, carbohydrates, minerals, vitamins, and other secondary metabolites. In vitro and in vivo pharmacological studies on the crude extracts, fractions, and isolated compounds from Lagochilus species showed hemostatic, antibacterial, anti-inflammatory, anti-allergic, cytotoxic, enzyme inhibitory, antispasmodic, hypotensive, sedative, psychoactive, and other activities.

scholarly journals Foeniculum vulgareMill: A Review of Its Botany, Phytochemistry, Pharmacology, Contemporary Application, and Toxicology

2014 ◽  
Vol 2014 ◽  
pp. 1-32 ◽  
Author(s):  
Shamkant B. Badgujar ◽  
Vainav V. Patel ◽  
Atmaram H. Bandivdekar
Keyword(s):  
Traditional Medicine ◽  
Scientific Evidence ◽  
New Drugs ◽  
Future Research ◽  
Foeniculum Vulgare ◽  
Wide Range ◽  
Research Findings ◽  
Valuable Compounds

Foeniculum vulgareMill commonly called fennel has been used in traditional medicine for a wide range of ailments related to digestive, endocrine, reproductive, and respiratory systems. Additionally, it is also used as a galactagogue agent for lactating mothers. The review aims to gather the fragmented information available in the literature regarding morphology, ethnomedicinal applications, phytochemistry, pharmacology, and toxicology ofFoeniculum vulgare. It also compiles available scientific evidence for the ethnobotanical claims and to identify gaps required to be filled by future research. Findings based on their traditional uses and scientific evaluation indicates thatFoeniculum vulgareremains to be the most widely used herbal plant. It has been used for more than forty types of disorders. Phytochemical studies have shown the presence of numerous valuable compounds, such as volatile compounds, flavonoids, phenolic compounds, fatty acids, and amino acids. Compiled data indicate their efficacy in severalin vitroandin vivopharmacological properties such as antimicrobial, antiviral, anti-inflammatory, antimutagenic, antinociceptive, antipyretic, antispasmodic, antithrombotic, apoptotic, cardiovascular, chemomodulatory, antitumor, hepatoprotective, hypoglycemic, hypolipidemic, and memory enhancing property.Foeniculum vulgarehas emerged as a good source of traditional medicine and it provides a noteworthy basis in pharmaceutical biology for the development/formulation of new drugs and future clinical uses.

scholarly journals Procyanidins are not bioavailable in rats fed a single meal containing a grapeseed extract or the procyanidin dimer B3

2002 ◽  
Vol 87 (4) ◽  
pp. 299-306 ◽  
Author(s):  
Jennifer L. Donovan ◽  
Adam Lee ◽  
Claudine Manach ◽  
Laurent Rios ◽  
Christine Morand ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Urinary Excretion ◽  
Ring Structure ◽  
Future Research ◽  
Human Gastrointestinal Tract ◽  
Human Diet ◽  
Single Meal ◽  
Nutritional Effects ◽  
Grapeseed Extract

Flavanols are the most abundant flavonoids in the human diet where they exist as monomers, oligomers and polymers. In the present study, catechin, the procyanidin dimer B3 and a grapeseed extract containing catechin, epicatechin and a mixture of procyanidins were fed to rats in a single meal. After the meals, catechin and epicatechin were present in conjugated forms in both plasma and urine. In contrast, no procyanidins or conjugates were detected in the plasma or urine of any rats. Procyanidins were not cleaved into bioavailable monomers and had no significant effects on the plasma levels or urinary excretion of the monomers when supplied together in the grapeseed extract. We conclude that the nutritional effects of dietary procyanidins are unlikely to be due to procyanidins themselves or monomeric metabolites with the intact flavonoid-ring structure, as they do not exist at detectable concentrations in vivo. Future research should focus on other procyanidin metabolites such as phenolic acids and on the effects of the unabsorbed oligomers and polymers on the human gastrointestinal tract.

scholarly journals Anti-Cancer Effects of Zotarolimus Combined with 5-Fluorouracil Treatment in HCT-116 Colorectal Cancer-Bearing BALB/c Nude Mice

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4683
Author(s):  
Geng-Ruei Chang ◽  
Chan-Yen Kuo ◽  
Ming-Yang Tsai ◽  
Wei-Li Lin ◽  
Tzu-Chun Lin ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tumor Growth ◽  
Nude Mice ◽  
Colorectal Adenocarcinoma ◽  
Transforming Growth Factor ◽  
Colon Adenocarcinoma ◽  
Future Research ◽  
Related Factors ◽  
Hct 116

Zotarolimus is a semi-synthetic derivative of rapamycin and an inhibitor of mammalian target of rapamycin (mTOR) signaling. Currently, zotarolimus is used to prolong the survival time of organ grafts, but it is also a novel immunosuppressive agent with potent anti-proliferative activity. Here, we examine the anti-tumor effect of zotarolimus, alone and in combination with 5-fluorouracil, on HCT-116 colorectal adenocarcinoma cells implanted in BALB/c nude mice. Compared with the control mice, mice treated with zotarolimus or zotarolimus combined with 5-FU showed retarded tumor growth; increased tumor apoptosis through the enhanced expression of cleaved caspase 3 and extracellular signal-regulated kinase (ERK) phosphorylation; reduced inflammation-related factors such as IL-1β, TNF-α, and cyclooxygenase-2 (COX-2) protein; and inhibited metastasis-related factors such as CD44, epidermal growth factor receptor (EGFR), transforming growth factor β (TGF-β), and vascular endothelial growth factor (VEGF). Notably, mice treated with a combination of zotarolimus and 5-FU showed significantly retarded tumor growth, reduced tumor size, and increased tumor inhibition compared with mice treated with 5-FU or zotarolimus alone, indicating a strong synergistic effect. This in vivo study confirms that zotarolimus or zotarolimus combined with 5-FU can be used to retard colorectal adenocarcinoma growth and inhibit tumorigenesis. Our results suggest that zotarolimus may increase the chemo-sensitization of tumor cells. Therefore, zotarolimus alone and zotarolimus combined with 5-FU may be potential anti-tumor agents in the treatment of human colon adenocarcinoma. Future research on zotarolimus may lead to the development of new therapeutic strategies.

CRISPR/Cas9 has introduced new gene therapy possibilities for muscular dystrophies

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Satellite Cells ◽  
Muscular Dystrophies ◽  
Future Research ◽  
Published Data ◽  
End Joining ◽  
Track Record ◽  
Effective Homology ◽  
Vector Targeting ◽  
Shape Of Nanoparticles

Advancements in using CRISPR/Cas9 have introduced a host of new therapy possibilities for muscular dystrophies (MDs). There is a definite feeling of hope in the industry, but other barriers lay ahead, and they will define the future of MD gene editing. The ambiguity surrounding AAV transduction of satellite cells in vivo must be explained so that, if required, effort may be focused on optimizing vector targeting. Although the satellite cell correction needs are evident, it must be determined experimentally if high muscle turnover has a deleterious effect on CRISPR approaches. Another issue with muscular HDR is its low editing efficiency. Even outside the MD, exogenous, effective DNA integration would open up a slew of new possibilities.Either conventional HDR must be upgraded, or alternative techniques must be developed. The fact that both myotubes and latent satellite cells are post-mitotic means the latter are the most effective. Homology-independent targeted integration (HITI), homology-mediated end joining (HMEJ) and prime editing are three novel potentials. Duplication removal is another technique to restore full-length proteins. Duplications are the second most frequent DMD mutation, and a single sgRNA technique was used to restore dystrophin. To date, CRISPR/Cas9-mediated duplication removal has only been evaluated in DMD patient cells and must be tested in vivo. Because of their demonstrated track record in in vivo research and clinical trials, AAVs are expected to be employed in early generations of MD CRISPR therapy. Currently, AAVs may be the biggest choice, but future drugs will almost probably require a different delivery approach. It may take the shape of nanoparticles, which may carry a large range of transiently expressed payloads, while being very variable. If satellite cells can not be repaired, their capacity to escape immune reactions is crucial. To decrease the effects of muscle turnover, re-administration of nanoparticles may be utilized to treat MD throughout one's life. However, effective nanoparticle dosing for CRISPR in vivo editing has yet to be established in the muscle. Because this was not an AAV problem, the focus should be on new compositions of nanoparticles rather than improving the CRISPR/Cas9 system. The lack of published data suggests that nanoparticles' systemic muscle transport remains a considerable challenge. Due to muscle volume in the human body and the need to target muscles within the thoracic cavity, local intramuscular injections are not practical. Future research will focus primarily on developing an effective, muscle-specific nanoparticle that can be administered through circulation. The challenges ahead are tremendous, but with the appropriate focus and resources, answers will emerge, bringing therapeutic genome editing closer to the clinic than ever. While this research focused on DMD, the mentioned principles and methodology may and will undoubtedly be extended to several other MDs.

Abstract 5402: Two Photon Microscopy Measurements Of Sub-epicardial Sarcomere Length In Perfused Rat Hearts

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Patrizia Camelliti ◽  
Gil Bub ◽  
Daniel J Stuckey ◽  
Christian Bollensdorff ◽  
Damian J Tyler ◽  
...  
Keyword(s):  
Sarcomere Length ◽  
Left Ventricular ◽  
Model Systems ◽  
Future Research ◽  
Fundamental Parameter ◽  
Rat Hearts ◽  
Perfused Hearts ◽  
Over Time

Sarcomere length (SL) is a fundamental parameter underlying the Frank Starling relation in the heart, as it offers an absolute representation of myocardial stretch. Previous studies addressed the Frank Starling relation by measuring SL in isolated myocytes or muscle strips. Here, we report first data obtained using a novel technique to measure sub-epicardial SL in perfused hearts. Rat hearts were Langendorff perfused (normal Tyrode solution) at a constant pressure of 90mmHg, labeled with the fluorescent membrane marker di-4-ANEPPS, and then arrested with high-K + Tyrode for either 2-photon microscopy (n=4) or MRI (n=4). Image analysis software was developed to extract SL at the cell level from >1,400 2-photon images (Fig 1 ) and correct for cell angle. SL increased by 10±2 % between 30 and 80 min of perfusion (1.98±0.04 to 2.17±0.03 μm; p<0.05; Fig 1 ). Measurements of left ventricular myocardial volume (LVMV) were made in vivo and in perfused hearts using 3D MRI. LVMV increased by 24±7% from in vivo to 30 min of perfusion, and by 11±3 % between 30 and 90 min (539±35; 664±44; 737±49 mm 3 , respectively; p<0.05; Fig 1 ). We show that SL can be measured in isolated perfused hearts. The method allowed monitoring of changes in SL over time, and showed that SL and LVMV increase to a similar extent during 30–80 min perfusion with crystalloid solution, probably due to tissue oedema. This result, together with the increase in LVMV during the first 30 min, highlights the pronounced differences between in vivo , in situ , and in vitro model systems for studies of cardiac physiology and mechanics. Future research will compare changes in SL in healthy hearts and disease models involving contractile dysfunction. Figure 1: Left: 2-photon microscopy image of di-4-ANEPPS labeled myocardium. Right: SL and LVMV changes over time.

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