Template-induced nucleation for controlling crystal polymorphism: from molecular mechanisms to applications in pharmaceutical processing

CrystEngComm ◽  
2019 ◽  
Vol 21 (28) ◽  
pp. 4122-4135 ◽  
Author(s):  
Jose V. Parambil ◽  
Sendhil K. Poornachary ◽  
Jerry Y. Y. Heng ◽  
Reginald B. H. Tan
Keyword(s):  
Molecular Mechanisms ◽  
Molecular Crystals ◽  
Pharmaceutical Manufacturing ◽  
Crystal Nucleation ◽  
Crystal Polymorphism ◽  
Pharmaceutical Processing ◽  
Major Factors ◽  
Templating Effect

The major factors governing template-induced nucleation of molecular crystals are assessed, highlighting applications in pharmaceutical manufacturing and formulation processes where the templating effect is used to promote crystal nucleation and for controlling crystal polymorphism.

Azobenzene Crystal Polymorphism Enables Tuneable Photoinduced Deformation, Mechanical Behaviors and Photoluminescent Properties

2021 ◽  
Author(s):  
Yunhui Hao ◽  
Lei Gao ◽  
Xiunan Zhang ◽  
Rongli Wei ◽  
Ting Wang ◽  
...  
Keyword(s):  
Smart Materials ◽  
Molecular Crystals ◽  
Stimuli Responsive ◽  
Mechanical Behaviors ◽  
Crystal Polymorphism

Stimuli-responsive molecular crystals are fascinating for their potential as adaptive smart materials. However, achieving one crystal that could respond to multiple stimuli and perform multiple functionalities simultaneously is still challenging....

scholarly journals Effects of obesity and estradiol on Na+/K+-ATPase and their relevance to cardiovascular diseases

2013 ◽  
Vol 218 (3) ◽  
pp. R13-R23 ◽  
Author(s):  
Milan Obradovic ◽  
Predrag Bjelogrlic ◽  
Manfredi Rizzo ◽  
Niki Katsiki ◽  
Mohamed Haidara ◽  
...  
Keyword(s):  
Atpase Activity ◽  
Molecular Mechanisms ◽  
Cardiac Tissue ◽  
Experimental Models ◽  
Cardiac Insufficiency ◽  
Sodium Potassium ◽  
Physiological Processes ◽  
Patients With Heart Failure ◽  
Major Factors ◽  
New Strategies

Obesity is associated with aberrant sodium/potassium-ATPase (Na+/K+-ATPase) activity, apparently linked to hyperglycemic hyperinsulinemia, which may repress or inactivate the enzyme. The reduction of Na+/K+-ATPase activity in cardiac tissue induces myocyte death and cardiac dysfunction, leading to the development of myocardial dilation in animal models; this has also been documented in patients with heart failure (HF). During several pathological situations (cardiac insufficiency and HF) and in experimental models (obesity), the heart becomes more sensitive to the effect of cardiac glycosides, due to a decrease in Na+/K+-ATPase levels. The primary female sex steroid estradiol has long been recognized to be important in a wide variety of physiological processes. Numerous studies, including ours, have shown that estradiol is one of the major factors controlling the activity and expression of Na+/K+-ATPase in the cardiovascular (CV) system. However, the effects of estradiol on Na+/K+-ATPase in both normal and pathological conditions, such as obesity, remain unclear. Increasing our understanding of the molecular mechanisms by which estradiol mediates its effects on Na+/K+-ATPase function may help to develop new strategies for the treatment of CV diseases. Herein, we discuss the latest data from animal and clinical studies that have examined how pathophysiological conditions such as obesity and the action of estradiol regulate Na+/K+-ATPase activity.

scholarly journals Peritubular Capillary Rarefaction: An Underappreciated Regulator of CKD Progression

2020 ◽  
Vol 21 (21) ◽  
pp. 8255
Author(s):  
Yujiro Kida
Keyword(s):  
Molecular Mechanisms ◽  
Significant Contribution ◽  
Basic Research ◽  
Peritubular Capillary ◽  
Ckd Progression ◽  
Hypertensive Nephrosclerosis ◽  
Capillary Rarefaction ◽  
Major Factors ◽  
Stage Renal Disease ◽  
End Stage

Peritubular capillary (PTC) rarefaction is commonly detected in chronic kidney disease (CKD) such as hypertensive nephrosclerosis and diabetic nephropathy. Moreover, PTC rarefaction prominently correlates with impaired kidney function and predicts the future development of end-stage renal disease in patients with CKD. However, it is still underappreciated that PTC rarefaction is a pivotal regulator of CKD progression, primarily because the molecular mechanisms of PTC rarefaction have not been well-elucidated. In addition to the established mechanisms (reduced proangiogenic factors and increased anti-angiogenic factors), recent studies discovered significant contribution of the following elements to PTC loss: (1) prompt susceptibility of PTC to injury, (2) impaired proliferation of PTC, (3) apoptosis/senescence of PTC, and (4) pericyte detachment from PTC. Mainly based on the recent and novel findings in basic research and clinical study, this review describes the roles of the above-mentioned elements in PTC loss and focuses on the major factors regulating PTC angiogenesis, the assessment of PTC rarefaction and its surrogate markers, and an overview of the possible therapeutic agents to mitigate PTC rarefaction during CKD progression. PTC rarefaction is not only a prominent histological characteristic of CKD but also a central driving force of CKD progression.

Crystal polymorphism of pharmaceuticals: probing crystal nucleation at the molecular level

2007 ◽  
Vol 22 (5) ◽  
pp. 550-555 ◽  
Author(s):  
Kevin P. Guiry ◽  
Joanne M. Kelleher ◽  
Simon E. Lawrence ◽  
Marie T. Mcauliffe ◽  
Humphrey A. Moynihan ◽  
...  
Keyword(s):  
Molecular Level ◽  
Crystal Nucleation ◽  
Crystal Polymorphism

scholarly journals Novel Regulatory Mechanisms of Pathogenicity and Virulence to Combat MDR inCandida albicans

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Saif Hameed ◽  
Zeeshan Fatima
Keyword(s):  
Drug Resistance ◽  
Molecular Mechanisms ◽  
Opportunistic Pathogen ◽  
Antifungal Drugs ◽  
Regulatory Mechanisms ◽  
Cross Resistance ◽  
Signaling Networks ◽  
Antifungal Drug Resistance ◽  
Human Fungal Pathogen ◽  
Major Factors

Continuous deployment of antifungals in treating infections caused by dimorphic opportunistic pathogenCandida albicanshas led to the emergence of drug resistance resulting in cross-resistance to many unrelated drugs, a phenomenon termed multidrug resistance (MDR). Despite the current understanding of major factors which contribute to MDR mechanisms, there are many lines of evidence suggesting that it is a complex interplay of multiple factors which may be contributed by still unknown mechanisms. Coincidentally with the increased usage of antifungal drugs, the number of reports for antifungal drug resistance has also increased which further highlights the need for understanding novel molecular mechanisms which can be explored to combat MDR, namely, ROS, iron, hypoxia, lipids, morphogenesis, and transcriptional and signaling networks. Considering the worrying evolution of MDR and significance ofC. albicansbeing the most prevalent human fungal pathogen, this review summarizes these new regulatory mechanisms which could be exploited to prevent MDR development inC. albicansas established from recent studies.

scholarly journals Effects of Aging on Activities of Mitochondrial Electron Transport Chain Complexes and Oxidative Damage in Rat Heart

2011 ◽  
pp. 281-289 ◽  
Author(s):  
Z. TATARKOVÁ ◽  
S. KUKA ◽  
P. RAČAY ◽  
J. LEHOTSKÝ ◽  
D. DOBROTA ◽  
...  
Keyword(s):  
Electron Transport ◽  
Oxidative Damage ◽  
Electron Transport Chain ◽  
Molecular Mechanisms ◽  
Thiol Group ◽  
Mitochondrial Electron Transport Chain ◽  
Age Related ◽  
Transport Chain ◽  
Old Rats ◽  
Major Factors

Mitochondrial dysfunction and accumulation of oxidative damage have been implicated to be the major factors of aging. However, data on age-related changes in activities of mitochondrial electron transport chain (ETC) complexes remain controversial and molecular mechanisms responsible for ETC dysfunction are still largely unknown. In this study, we examined the effect of aging on activities of ETC complexes and oxidative damage to proteins and lipids in cardiac mitochondria from adult (6-month-old), old (15-month-old) and senescent (26-month-old) rats. ETC complexes I-IV displayed different extent of inhibition with age. The most significant decline occurred in complex IV activity, whereas complex II activity was unchanged in old rats and was only slightly reduced in senescent rats. Compared to adult, old and senescent rat hearts had significantly higher levels of malondialdehyde, 4-hydroxynonenal (HNE) and dityrosine, while thiol group content was reduced. Despite marked increase in HNE content with age (25 and 76 % for 15- and 26-month-old rats, respectively) Western blot analysis revealed only few HNE-protein adducts. The present study suggests that non-uniform decline in activities of ETC complexes is due, at least in part, to mitochondrial oxidative damage; however, lipid peroxidation products appear to have a limited impact on enzyme functions.

scholarly journals Epilepsy-associated mutations in the voltage sensor of KCNQ3 affect voltage dependence of channel opening

2018 ◽  
Vol 151 (2) ◽  
pp. 247-257 ◽  
Author(s):  
Rene Barro-Soria
Keyword(s):  
Unnatural Amino Acids ◽  
Molecular Mechanisms ◽  
Neuronal Excitability ◽  
Voltage Dependence ◽  
Therapeutic Potential ◽  
Voltage Sensor ◽  
Voltage Range ◽  
M Current ◽  
Channel Opening ◽  
Major Factors

One of the major factors known to cause neuronal hyperexcitability is malfunction of the potassium channels formed by KCNQ2 and KCNQ3. These channel subunits underlie the M current, which regulates neuronal excitability. Here, I investigate the molecular mechanisms by which epilepsy-associated mutations in the voltage sensor (S4) of KCNQ3 cause channel malfunction. Voltage clamp fluorometry reveals that the R230C mutation in KCNQ3 allows S4 movement but shifts the open/closed transition of the gate to very negative potentials. This results in the mutated channel remaining open throughout the physiological voltage range. Substitution of R230 with natural and unnatural amino acids indicates that the functional effect of the arginine residue at position 230 depends on both its positive charge and the size of its side chain. I find that KCNQ3-R230C is hard to close, but it is capable of being closed at strong negative voltages. I suggest that compounds that shift the voltage dependence of S4 activation to more positive potentials would promote gate closure and thus have therapeutic potential.

scholarly journals The Hepatoprotection by Oleanolic Acid Preconditioning: Focusing on PPARαActivation

PPAR Research ◽  
2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Wenwen Wang ◽  
Kan Chen ◽  
Yujing Xia ◽  
Wenhui Mo ◽  
Fan Wang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Oleanolic Acid ◽  
Molecular Mechanisms ◽  
Liver Enzymes ◽  
Acute Liver Injury ◽  
Inflammatory Factors ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Anti Inflammatory ◽  
Major Factors

Objective. Previous studies have characterized the hepatoprotective and anti-inflammatory properties of oleanolic acid (OA). This study aimed to investigate the molecular mechanisms of OA hepatoprotection in concanavalin A- (ConA-) induced acute liver injury.Materials and Methods. ConA (20 mg/kg) was intravenously injected to induce acute liver injury in Balb/C mice. OA pretreatment (20, 40, and 80 mg/kg) was administered subcutaneously once daily for 3 consecutive days prior to treatment with ConA; 2, 8, and 24 h after ConA injection, the levels of serum liver enzymes and the histopathology of major factors and inflammatory cytokines were determined.Results. OA reduced the release of serum liver enzymes and inflammatory factors and prevented ConA mediated damage to the liver. OA elevated the expression levels of peroxisome proliferator-activated receptor alpha (PPARα) and decreased the phosphorylation of c-Jun NH2-terminal kinase (JNK).Conclusion. OA exhibits anti-inflammatory properties during ConA-induced acute liver injury by attenuating apoptosis and autophagy through activation of PPARαand downregulation of JNK signaling.

scholarly journals The Mechanisms of Peripheral Nerve Preconditioning Injury on Promoting Axonal Regeneration

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Xiaoyan Yang ◽  
Ruixuan Liu ◽  
Ying Xu ◽  
XiangYu Ma ◽  
Bing Zhou
Keyword(s):  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Axonal Regeneration ◽  
Molecular Mechanisms ◽  
Lipid Synthesis ◽  
Nerve Lesion ◽  
Axonal Regrowth ◽  
Cord Injury ◽  
Major Factors

Two major factors contribute to the failure of axonal regrowth in the central nervous system (CNS), namely, the neuronal intrinsic regenerative capacity and the extrinsic local inhibitory microenvironments. However, a preconditioning peripheral nerve lesion could substantially enhance the regeneration of central axons following a subsequent spinal cord injury. In the present review, we summarize the molecular mechanisms of the preconditioning injury effect on promoting axonal regeneration. The injury signal transduction resulting from preconditioning peripheral nerve injury regulates the RAG expression to enhance axonal regeneration. Importantly, preconditioning peripheral nerve injury triggers interactions between neurons and nonneuronal cells to amplify and maintain their effects. Additionally, the preconditioning injury impacts mitochondria, protein, and lipid synthesis. All these coordinated changes endow axonal regeneration.

In Vitro Effects of Cementum Protein 1 (CEMP1) on Calcium Phosphate Crystal Formation and its Role During the Mineralization Process

2009 ◽  
Vol 1244 ◽  
Author(s):  
Enrique Romo-Arévalo ◽  
Eduardo Villarreal-Ramírez ◽  
Juan L. Chávez-Pacheco ◽  
Cristina Piña-Barba ◽  
M. Aguilar-Franco ◽  
...  
Keyword(s):  
Calcium Phosphate ◽  
Molecular Mechanisms ◽  
Periodontal Regeneration ◽  
Octacalcium Phosphate ◽  
Cellular Adhesion ◽  
Crystal Nucleation ◽  
Crystal Formation ◽  
Calcium Phosphate Crystal ◽  
Hydroxyapatite Crystals

ABSTRACTCementum contains specific molecules that could serve to identify, isolate and characterize the cementoblast lineage and to determine the cellular and molecular mechanisms that regulate the cementogenesis process, since it plays a key role during the periodontal regeneration process. One of these molecules is the human cementum protein 1 (CEMP1); which has a molecular weight of 25,9 kDa. In vitro experiments have shown that CEMP1 promotes cellular adhesion and differentiation. In addition, this protein has been implied in regulating the degree of deposition, composition and morphology of hydroxyapatite crystals formed by putative cementoblast in vitro. Therefore, it is possible that CEMP1 promotes the formation, growth and regulates the morphology of hydroxyapatite crystals in vitro. We have produced a human recombinant CEMP1 (hrCEMP1) in a prokaryotic system. The hrCEMP1 purification was realized using the column NiTA HisPrep FF/16. Assays of calcium phosphate crystal growth were realized by means of capillary counterdiffusion system. Our results demonstrated that hrCEMP1 promotes octacalcium phosphate crystal nucleation and possesses high affinity for hydroxyapatite. We infer that hrCEMP1 plays a key role during the regeneration of mineralized tissues.

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