Skeletal, dentoalveolar and soft tissue changes after stabilization splint treatment for patients with temporomandibular joint disorders.

BACKGROUND: Temporomandibular disorder (TMD) is a grouping of heterogeneous disorders with multifactorial origins. Stabilization splints (SS) have demonstrated an acceptable treatment effect in TMD. The possible changes at the skeletal, dental, and soft tissue levels need to be addressed to evaluate the benefit/risk ratio of this therapeutic procedure. Accordingly, this study aimed to three­dimensionally evaluate skeletal, dentoalveolar and soft tissue changes after SS treatment for patients with TMD. METHODS: This retrospective study included 74 adult patients with myofascial and/or intra-articular disorders (25 males and 49 females), with an average age of 22.88 ± 4.8 years, who underwent SS treatment. Pre- and post-treatment Cone beam computed tomography were analysed using Invivo 6.0.3 software. The primary outcome was the vertical skeletal and dentoalveolar changes, while the secondary outcomes were the anteroposterior skeletal, dentoalveolar and soft tissue changes. Paired t-test and Wilcoxon rank sum test were used for statistical analyses. RESULTS: For the primary outcome; skeletally, there was a significant increase in mandibular plane inclination (difference: 0.82°±1.37), decrease facial height ratio (difference: 0.45%±1.07) and at the dentoalveolar level, the inclination of the functional (FOP-SN, FOP-FH) and bisecting (BOP-SN, BOP-FH) occlusal planes exhibited a significant increase too (difference: 0.38 ± 1.43°, 0.49 ± 1.62°, 0.44 ± 1.29° and 0.41 ± 1.17°, respectively) and also a decrease in the overbite (difference: -0.54 ± 0.83). For the secondary outcomes; there was a significant decrease in mandibular position (SNB) (difference: 1.60 ± 1.36°) and increase in the overjet (difference: 0.93 ± 1.04, p < 0.001) and a significant lower lip retrusion (difference: 0.33 ± 1.01 mm p < 0.01), was observed too. CONCLUSIONS: SS therapy resulted in significant vertical skeletal and dentoalveolar changes that were manifested mainly by facial height ratio, mandibular and occlusal plane changes, and to a lesser extent, significant anteroposterior skeletal, dentoalveolar, and soft tissue changes in the form of mandibular position, increased overjet and a more retrusive lower lip. These changes should be considered during patients' selection prior to initiating SS therapy.

Quantitative and qualitative condylar changes following stabilization splint therapy in patients with temporomandibular joint disorders with and without skeletal lateral mandibular asymmetry: a cone beam computed tomographic study.

BACKGROUND: Temporomandibular disorders (TMDs) encompass pain and dysfunction in the jaw, muscles, and adjacent structures. This study aimed to explore the quantitative (condylar position, morphology) and qualitative (bone mineral density (BMD)) therapeutic outcomes following a stabilization splint (S.S.) therapy in adult patients diagnosed with TMD (Arthralgia) with/without lateral mandibular asymmetry (MA) using cone beam computed tomography (CBCT). METHODS: In this retrospective clinical study, 60 adult TMD patients who received S.S. therapy were enrolled and allocated into the TMD group (TMDG) and TMD with MA group (TMD + MAG). The diagnosis was made according to the Diagnostic Criteria for TMD (DC/TMD) AXIS I. MA was measured from the mid-sagittal plane to the Menton point. CBCT was used to scan the temporomandibular joints pre- (T0) and post- (T1)-treatment for three-dimensional analysis. Intra- and intergroup statistical comparisons were performed using the Wilcoxon signed ranks and the Kruskal‒Wallis test. RESULTS: For quantitative comparisons, there was a statistically significant difference between T0 and T1 in the joint spaces of TMD + MAG (anterior, superior, posterior, and coronal lateral on the deviated side as well as in the superior, coronal medial joint space of the contralateral side). Morphologically, the deviated side had a narrower condylar width, reduced condylar height, and a steeper eminence angle. In contrast, the contralateral side tended to have a greater condylar length. For qualitative measurements, BMD also showed statistical significance between T0 and T1 in the majority of the condyle slopes (AS, SS, PS, and LS on the deviated side and in AS and MS on the contralateral side) of TMD + MAG. Additionally, only the AS and PS showed significance in TMDG. CONCLUSION: Multiple joint space widening (AJS and CMS) and narrowing (SJS, PJS, and CLS) could characterize the deviated side in TMD + MA. Factors like narrower condylar width, reduced condylar height, and steeper eminence angle on the deviated side can worsen TMD + MA. Proper alignment of the condyle-disc position is essential for optimal function and load distribution, potentially affecting bone mineral density (BMD). MA plays a prominent role in disturbing bone densities. S.S. therapy shows more evident outcomes in TMD + MAG (on the deviated side compared to the contralateral side) than the TMDG.

COSMIC: a curated database of somatic variants and clinical data for cancer.

The Catalogue Of Somatic Mutations In Cancer (COSMIC), https://cancer.sanger.ac.uk/cosmic, is an expert-curated knowledgebase providing data on somatic variants in cancer, supported by a comprehensive suite of tools for interpreting genomic data, discerning the impact of somatic alterations on disease, and facilitating translational research. The catalogue is accessed and used by thousands of cancer researchers and clinicians daily, allowing them to quickly access information from an immense pool of data curated from over 29 thousand scientific publications and large studies. Within the last 4 years, COSMIC has substantially expanded its utility by adding new resources: the Mutational Signatures catalogue, the Cancer Mutation Census, and Actionability. To improve data accessibility and interoperability, somatic variants have received stable genomic identifiers that are associated with their genomic coordinates in GRCh37 and GRCh38, and new export files with reduced data redundancy have been made available for download.

A comprehensive review of discovery and development of drugs discovered from 2020-2022.

To fully evaluate and define the new drug molecule for its pharmacological characteristics and toxicity profile, pre-clinical and clinical studies are conducted as part of the drug research and development process. The average time required for all drug development processes to finish various regulatory evaluations ranges from 11.4 to 13.5 years, and the expense of drug development is rising quickly. The development in the discovery of newer novel treatments is, however, largely due to the growing need for new medications. Methods to identify Hits and discovery of lead compounds along with pre-clinical studies have advanced, and one example is the introduction of computer-aided drug design (CADD), which has greatly shortened the time needed for the drug to go through the drug discovery phases. The pharmaceutical industry will hopefully be able to address the present and future issues and will continue to produce novel molecular entities (NMEs) to satisfy the expanding unmet medical requirements of the patients as the success rate of the drug development processes is increasing. Several heterocyclic moieties have been developed and tested against many targets and proved to be very effective. In-depth discussion of the drug design approaches of newly found drugs from 2020 to 2022, including their pharmacokinetic and pharmacodynamic profiles and in-vitro and in-vivo assessments, is the main goal of this review. Considering the many stages these drugs are going through in their clinical trials, this investigation is especially pertinent. It should be noted that synthetic strategies are not discussed in this review; instead, they will be in a future publication.

Help biocurators to maximize the reach of your data.

Curated scientific databases catalogue and amplify research findings to maximize their reach. Authors should write their papers with this in mind, ensuring that data are accurate, easy to extract, and presented in standardized formats.

Bioassays guided isolation of berberine from Berberis lycium and its neuroprotective role in aluminium chloride induced rat model of Alzheimer's disease combined with insilico molecular docking.

OBJECTIVE: Berberis lycium is an indigenous plant of Pakistan that is known for its medicinal properties. In the current study, we investigated the anti-Alzheimer's effect of berberine isolated from Berberis lycium. METHODS: Root extract of B. lycium was subjected to acetylcholinesterase inhibition assay and column chromatography for bioassays guided isolation of a compound. The neuroprotective and memory improving effects of isolated compound were evaluated by aluminium chloride induced Alzheimer's disease rat model, elevated plus maze (EPM) and Morris water maze (MWM) tests., Levels of dopamine and serotonin in rats brains were determined using HPLC. Moreover, western blot and docking were performed to determine interaction between berberine and ß-secretase. RESULTS: During fractionation, ethyl acetate and methanol (3:7) fraction was collected from solvent mixture of ethyl acetate and methanol. This fraction showed the highest anti-acetylcholinesterase activity and was alkaloid positive. The results of TLC and HPLC analysis indicated the presence of the isolated compound as berberine. Additionally, the confirmation of isolated compound as berberine was carried out using FTIR and NMR analysis. In vivo EPM and MWM tests showed improved memory patterns after berberine treatment in Alzheimer's disease model. The levels of dopamine, serotonin and activity of antioxidant enzymes were significantly (p<0.05) enhanced in brain tissue homogenates of berberine treated group. This was supported by decreased expression of ß-secretase in berberine treated rat brain homogenates and good binding affinity of berberine with ß-secretase in docking studies. Binding energies for interaction of ß-secretase with berberine and drug Rivastigmine is -7.0 kcal/mol and -5.8 kcal/mol respectively representing the strong interactions. The results of docked complex of secretase with berberine and Rivastigmine was carried out using Gromacs which showed significant stability of complex in terms of RMSD and radius of gyration. Overall, the study presents berberine as a potential drug against Alzheimer's disease by providing evidence of its effects in improving memory, neurotransmitter levels and reducing ß-secretase expression in the Alzheimer's disease model.

Three-dimensional evaluation of upper pharyngeal airway, hyoid bone, and craniocervical changes following stabilization splint therapy in adult patients with temporomandibular joint disorders and mandibular deviation: A retrospective study.

OBJECTIVE: This study aimed primarily to analyze the three-dimensional (3D) changes in the pharyngeal airway (PA), and secondarily, the hyoid bone (HB) and the craniocervical (CC) following stabilization splint (SS) therapy in adult patients with temporomandibular joint disorders (TMD) and mandibular deviation (MD). METHODS: Thirty-five adult patients with TMD and MD, who were treated using SS with a mean age of 25.14 ± 6.11 years, were enrolled in this retrospective clinical study. Pre- and post-therapeutic cone-beam computed tomography (CBCT) scans were analyzed. PA dimension,nasopharyngeal, oropharyngeal, hypopharyngeal, sub-hypopharyngeal, and total pharyngeal airway spaces were measured in surface area, volume, minimum constricted area (MCA) and width, HB position, and CC posture were analyzed three-dimensionally using InVivo 6.0.3 and Dolphin 11.95 software. Wilcoxon rank-sum or Paired t-test was conducted, and P < 0.05 was considered significant. RESULTS: SS therapy was administered for a period of 9.49 ± 4.02 months. The oropharyngeal airway space showed a significant decrease in sagittal width. The hypopharyngeal surface area, volume, MCA, and sagittal width decreased significantly. In terms of HB, hyoid-mandibular plane (H-MP), retrognathia-third vertebra's most inferior-anterior (RGN-C3ia), and retrognathia-Sella (RGN-S) distances significantly decreased. The Nasion-Sella line and the line that passes through C2ip to the odontoid process posterior tangent (NSL-OPT) angle in CC posture also decreased significantly. CONCLUSION: SS therapy in TMD patients with MD mainly results in narrowing of the hypopharyngeal region, no change in HB position and improvement in head posture. These results undoubtedly assist in diagnosis and treatment of clinical conditions.

Molecular implications of glycosaminoglycans in diabetes pharmacotherapy.

Diabetes mellitus causes a wide range of metabolic derangements with multiple organ damage. The microvascular and macrovascular complications of diabetes result partly from the damage to the glycosaminoglycans (GAG) in the basement membrane. GAGs are negatively charged polysaccharides with repeating disaccharide units. They play a significant role in cellular proliferation and signal transduction. Destruction of extracellular matrix results in diseases in various organs including myocardial fibrosis, retinal damage and nephropathy. To substitute the natural GAGs pharmacotherapeutically, they have been synthesized by using basic disaccharide units. Among the four classes of GAGs, heparin is the most widely studied. Recent studies have revealed multiple significant GAG-protein interactions suggesting their use for the management of diabetic complications. Moreover, they can act as biomarkers for assessing the disease progression. A number of GAG-based therapeutic agents are being evaluated for managing diabetic complications. The current review provides an outline of the role of GAGs in diabetes while covering their interaction with different molecular players that can serve as targets for the diagnosis, management and prevention of diabetes and its complications. The medicinal chemistry and clinical pharmacotherapeutics aspects have are covered to aid in the establishment of GAG-based therapies as a possible avenue for diabetes.

Quercus floribunda Lindl. Ex A. Camus; a tremendous remedy against inflammation and associated symptoms.

Crude extracts prepared from aerial parts and nut galls of Quercus floribunda Lindl. Ex. A. Camus were evaluated for phytochemical screening, in vitro antioxidant, and in vivo analgesic, anti-inflammatory and antipyretic activities. Various solvents including methanol (M), acetone (A), distilled water (DW), distilled water + methanol (DWM) were used for extraction. Highest total phenolic (66.9 ± 0.05 µg GAE/mgE) and flavonoid content (38.4 ± 0.72 µg QE/mgE) were measured in QFAA extract by colorimetric methods. Cumulative maximum concentrations of polyphenols were quantified in QFMG, QFAA, and QFMA extracts i.e. 19.036, 15. 574 and 11.647 µg/mg of extract by RP-HPLC analysis. From aerial parts extracts, apentacyclic tritepenoid, glutinol was isolated using column chromatography techniques and structure was elucidated using spectroscopic techniques. QFDWMA (205.5 ± 0.56 µg AAE/mg of extract) showed highest total reducing power while highest total antioxidant capacity (207.1 ± 0.49 AAE/mg of extract) and free radical scavenging potential (96.1 ± 0.42%) were observed in QFAA extract. QFAA extract showed significant (p ≤ 0.001) analgesic potential in different pain models i.e. hot plate method, cold plate method, Haffner's tail clip method and acetic acid induced writhing assay having 50.20%, 62.07%, 57.26% and 70.49% analgesia respectively at 300 mg/kg. QFAA extract showed maximum anti-inflammatory activity in croton oil induced edema (68.83%) and in carrageenan induced paw edema models (72.32%) at 300 mg/kg concentration. QFAA extract markedly reduced the rectal temperature at 300 mg/kg concentration, in brewer's yeast induced pyrexia model. Detailed investigations can be executed in future to determine the molecular mechanisms of these pharmacological attributes.

Synthesis, In Silico Studies, and Antioxidant and Tyrosinase Inhibitory Potential of 2-(Substituted Phenyl) Thiazolidine-4-Carboxamide Derivatives.

Heterocyclic nuclei have shown a wide variety of biological activities, highlighting their importance in drug discovery. Derivatives of 2,4-subsituted thiazolidine have a structural similarity with the substrates of tyrosinase enzymes. Hence, they can be used as an inhibitor to compete against tyrosine in the biosynthesis of melanin. This study is focused on design, synthesis, biological activities, and in silico studies of thiazolidine derivatives substituted at positions 2 and 4. The synthesized compounds were evaluated to determine the antioxidant activity and tyrosine inhibitory potential using mushroom tyrosinase. The most potent tyrosinase enzyme inhibitor was compound 3c having IC50 value 16.5 ± 0.37 µM, whereas compound 3d showed maximum antioxidant activity in a DPPH free radical scavenging assay (IC50 = 18.17 µg/mL). Molecular docking studies were conducted using mushroom tyrosinase (PDB ID: 2Y9X) to analyze binding affinities and binding interactions of the protein-ligand complex. Docking results indicated that hydrogen bonds and hydrophobic interactions were mainly involved in the ligand and protein complex. The highest binding affinity was found to be -8.4 Kcal/mol. These results suggest that thiazolidine-4-carboxamide derivatives could serve as lead molecules for development of novel potential tyrosinase inhibitors.

Ovarian Vein Thrombosis: An Unusual Cause of Abdominal Pain in Breast Cancer.

Ovarian vein thrombosis (OVT) is a rare but potentially life-threatening complication that is usually seen in the intrapartum or postpartum period but can also be seen in patients with risk factors for venous thromboembolism. When symptomatic, it usually presents with abdominal pain and other vague constitutional symptoms, hence it is important for healthcare professionals to be aware of this condition when evaluating patients with risk factors. We present a rare case of OVT in a patient with breast cancer. Due to a lack of clear guidelines regarding the treatment and duration of treatment in non-pregnancy-related OVT, we followed the guidelines for the treatment of venous thromboembolism and started the patient on rivaroxaban for a three-month duration with close outpatient follow-up.

Quantitative and qualitative condylar changes following stabilization splint therapy in patients with temporomandibular joint disorders.

OBJECTIVE: This study aimed to explore the quantitative and qualitative condylar changes following stabilization splint (S.S) therapy, including condylar position, morphology, and bone mineral density (BMD) in subjects with temporomandibular disorders (TMD). MATERIALS AND METHODS: In this retrospective clinical study, we enrolled 40 TMD subjects (80 joints) aged 18 to 35 years, for whom a S.S was used to treat TMD. The 80 TMD consists of 32 masticatory muscle disorders (myalgia) and 48 TMJ disorders (arthralgia). Cone beam computed tomography (CBCT) was used to scan the TMJs of subjects pre- and post-treatment for three-dimensional analysis (3D). Using Mimics software v.21.0, quantitative (3D condylar and joint spaces dimensions parameters were measured using linear measurements in millimeters, according to the Kamelchuk method and Ikeda method, while the assessment of anteroposterior condyle position within the glenoid fossa was based on the method of Pullinger and Hollender), and qualitative (a round bone tissue with an area of 2 mm2 in three representative areas according to the Kamelchuk method to measure condylar BMD) pre- and post-treatment. Intra- and inter-group statistical comparisons were performed using the Wilcoxon signed ranks and the Kruskal-Wallis test, respectively. RESULTS: The course of treatment was 6-12 months, with an average of 9.1 months. For the pre- and post-treatment quantitative comparisons, there was a statistically significant difference in the anterior joint space (AJS) and coronal medial space, as well as the condyle length in the myalgia group and condylar width in the arthralgia group. For qualitative measurements, a significant difference was observed in the posterior slope of the myalgia group and the arthralgia group's anterior, superior, and posterior slopes. The inter-group comparisons revealed significant differences in AJS, condylar length, and anterior slope density. CONCLUSION: In short-term follow-up, the S.S influenced patients with TMD from different origins; it changes anterior and coronal medial joint space, condyle length in myalgia, and width in arthralgia. Furthermore, it improved the condyle bone density more evidently in arthralgia. CLINICAL RELEVANCE: This study highlights the influence of S.S on symptomatic populations with TMD of different origins from a qualitative and quantitative perspective.

A Rare Case of an Adrenal Schwannoma.

Schwannomas are tumors of neoplastic Schwann cells generally found in peripheral nerves in the head, neck, and extremities. They do not demonstrate hormonal abnormalities, and initial symptoms are typically secondary to adjacent organ compression. These tumors are rarely found in the retroperitoneum. We present a rare finding of an adrenal schwannoma in a 75-year-old female who presented to the emergency department with right flank pain. Imaging incidentally demonstrated a 4.8 cm left adrenal mass. Ultimately, she underwent a left robotic adrenalectomy, and immunohistochemical testing confirmed the presence of an adrenal schwannoma. It is imperative to undergo adrenalectomy and immunohistochemical testing to confirm the diagnosis and rule out malignancy.

Three dimensional evaluation of the skeletal and temporomandibular joint changes following stabilization splint therapy in patients with temporomandibular joint disorders and mandibular deviation: a retrospective study.

BACKGROUND: Three-dimensional (3D) detailed evaluations of the mandibular mediolateral position, mandibular condylar position, and temporomandibular joint (TMJ) spaces following stabilization splints (SS) therapy in patients with temporomandibular joint disorders (TMD) and mandibular deviation (MD) have not been reported in the available literature. Accordingly, this study aimed to three-dimensionally analyze the skeletal and bony temporomandibular joint changes following stabilization splint therapy in adult patients with temporomandibular joint disorders and mandibular deviation. METHODS: This study is a retrospective clinical study that enrolled 26 adult patients with TMD and MD with a mean age of 24.86 years. The Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) was used to diagnose TMD. SS was adjusted weekly until occlusal contact stabilization occurred, and then adjusted monthly, patients were instructed to wear it at night for at least 10 h. The SS was removed after the elimination of TMD symptoms (TMJ/muscle pain on palpation, muscle spasm, and clicking) and having both condyles completely seated in a musculoskeletally stable position. Pre- and post-therapeutic Cone Beam Computed Tomography (CBCT) was analyzed. Mandibular mediolateral position, TMJ spaces, and mandibular condyle position were analyzed three-dimensionally using Mimics 21.0 software. Paired t-test or Wilcoxon rank-sum test was performed, and the significance level was considered at P < 0.05. RESULTS: The treatment period with SS therapy was 10.07 ± 3.1 months. The deviated chin was improved in 69.23% of the sample; the range of improvement was > 0 mm ≤ 3.9 mm. The mandibular rotation was significantly decreased from 3.58 ± 2.02° to 3.17 ± 1.60. The deviated side's superior and posterior joint TMJ spaces were significantly increased from 2.49 ± 0.88 mm and 1.25 ± 0.79 mm to 2.98 ± 1.02 mm and 1.86 ± 0.72 mm, respectively. The value of the difference from the bilateral condyle head position to the X and Z axes significantly decreased from 2.50 ± 1.56 mm and 2.30 ± 1.57 mm to 1.64 ± 1.58 mm and 1.82 ± 1.11 mm, respectively. CONCLUSION: The main positional effect of the stabilization splint treatment in TMD patients with MD includes considerable correction of mandibular deviation, improving facial asymmetry, and moving the condyle into a stable condylar position; these were done by promoting the mandible to rotate around the Z (roll) and Y (yaw) axes and by forward, downward, and outward condylar movement on the deviated side, respectively.

Friedelin Attenuates Neuronal Dysfunction and Memory Impairment by Inhibition of the Activated JNK/NF-κB Signalling Pathway in Scopolamine-Induced Mice Model of Neurodegeneration.

Oxidative stress (OS) and c-Jun N-terminal kinase (JNK) are both key indicators implicated in neuro-inflammatory signalling pathways and their respective neurodegenerative diseases. Drugs targeting these factors can be considered as suitable candidates for treatment of neuronal dysfunction and memory impairment. The present study encompasses beneficial effects of a naturally occurring triterpenoid, friedelin, against scopolamine-induced oxidative stress and neurodegenerative pathologies in mice models. The treated animals were subjected to behavioural tests i.e., Y-maze and Morris water maze (MWM) for memory dysfunction. The underlying mechanism was determined via western blotting, antioxidant enzymes and lipid profile analyses. Molecular docking studies were carried out to predict the binding modes of friedelin in the binding pocket of p-JNK protein. The results reveal that scopolamine caused oxidative stress by (1) inhibiting catalase (CAT), peroxidase enzyme (POD), superoxide dismutase (SOD), and reduced glutathione enzyme (GSH); (2) the up-regulation of thiobarbituric acid reactive substances (TBARS) in mice brain; and (3) affecting the neuronal synapse (both pre- and post-synapse) followed by associated memory dysfunction. In contrast, friedelin administration not only abolished scopolamine-induced oxidative stress, glial cell activation, and neuro-inflammation but also inhibited p-JNK and NF-κB and their downstream signaling molecules. Moreover, friedelin administration improved neuronal synapse and reversed scopolamine-induced memory impairment accompanied by the inhibition of ß-secretase enzyme (BACE-1) to halt amyloidogenic pathways of amyloid-ß production. In summary, all of the results show that friedelin is a potent naturally isolated neuro-therapeutic agent to reverse scopolamine-induced neuropathology, which is characteristic of Alzheimer's disease.

Green nanoparticles as multifunctional nanomedicines: Insights into anti-inflammatory effects, growth signaling and apoptosis mechanism in cancer.

Recently, green nanotechnology got great attention due to their reliable, sustainable, and eco-friendly synthesis protocols. The green nanoparticles (GNPs) are preferred over chemically synthesized nanoparticles owing to less destructive effects associated with the synthesis procedures as well as therapeutic involvement. In this review, we have discussed the applications of GNPs in inflammation-mediated disorders, with special emphasis on cancer, initiated due to oxidative stress and inflammatory cascade. Real-time mechanism based studies on GNPs have suggested their anticancer effects through inducing apoptosis, inhibiting angiogenesis, tissue invasion metastasis, reduced replicative capabilities in addition to target specific different signaling molecules and cascades involved in the development or progression of cancer. Moreover, the association of GNPs with the inhibition or induction of autophagy for the management of cancer has also been discussed. A large number of studies showed the GNPs have multifunctional biomedical properties of theranostic prominence. Therefore, the development of GNPs with naturally established systems could upsurge their definite applications as biomedicines including target specific destruction of the cancerous cells.

Effect of Tensile Frequency on the Osteogenic Differentiation of Periodontal Ligament Stem Cells.

Purpose: The role of periodontal ligament stem cells (PDLSCs) in mediating osteogenesis involved in orthodontic tooth movement (OTM) is well established. However, various relevant in vitro studies vary in the frequency of tension. The effect of tensile frequency on the mechanotransduction of PDLSCs is not clear. The current study aimed to determine the effect of different tensile frequencies on the osteogenic differentiation of PDLSCs and to identify important mechano-sensitivity genes. Methods: Human PDLSCs were isolated, identified, and subjected to cyclic equibiaxial tensile strain of 12% at different frequencies of 0.1 Hz, 0.5 Hz, 0.7 Hz, or static cultures. Osteogenic differentiation of PDLSCs was assessed by using Western blotting. High-throughput sequencing was used to identify differential mRNA expression. Short time-series expression miner (STEM) was utilized to describe the frequency patterns of the mRNAs. The functions and enriched pathways were identified, and the hub genes were identified and validated. Results: We found that the osteoblastic differentiation capacity of PDLSCs increased with tensile frequency in the range of 0.1-0.7 Hz. Eight frequency-tendency gene expression profiles were identified to be statistically significant. Tensile frequency-specific expressed genes, such as SALL1 and EYA1, which decreased with the increase in tensile frequency, were found. Conclusion: The osteoblastic differentiation of PDLSCs under mechanical tensile force is frequency dependent. EYA1 and SALL1 were identified as potential important tensile frequency-sensitive genes, which may contribute to the cyclic tension-induced osteogenic differentiation of PDLSCs in a frequency-dependent manner.

Thoracic Epidural Versus General Anaesthesia For Laparoscopic Cholecystectomy: A Randomized Controlled Trial.

BACKGROUND: Laparoscopic cholecystectomy is one of the most commonly performed surgeries worldwide. Aim of our study was to compare the effectiveness of thoracic epidural anaesthesia with general anaesthesia for Laparoscopic cholecystectomy in terms of changes in blood pressure during surgery, postoperative pain, respiratory complications and average length of hospital stay. It was a randomized controlled trial conducted from 1stOctober 2018 to 31st October 2019. METHODS: Eightytwo patients planned to undergo elective laparoscopic cholecystectomy were randomly divided into two groups, T and G. In Group T all patients underwent laparoscopic cholecystectomy under thoracic epidural anaesthesia with 12 ml of 0.25% bupivacaine and 1% lignocaine plain whereas in group G all patients underwent surgery under general anaesthesia. Intra-operative mean arterial pressure (MAP) and postoperative opioid consumption in first 24hrs were recorded as primary outcomes whereas presence or absence of respiratory complication and duration of hospital stay as secondary outcome.. RESULTS: Out of 82 patients, 41 patients underwent laparoscopic cholecystectomy under thoracic epidural anaesthesia and 41 patients had surgery under general anaesthesia. Mean arterial pressure was lower in Group T and the difference was statistically significant. The average time of first complaint of postoperative pain in Group T was 5.4±1.26 hours as compared to less than 0.79±0.25 hours in Group G. Patients in group T required lower doses of opioid analgesia in first twenty-four hours as compared to patients in group G. Mean hospital stay in group T was 1 day as compared to 3 days in group G. CONCLUSIONS: Thoracic epidural anaesthesia provides a better alternative to general anaesthesia for Laparoscopic cholecystectomy with lower intraoperative mean arterial blood pressure, 24 hours postoperative consumption of opioids, respiratory complications and length of hospital stay.

Cordyceps militaris as a Bio Functional Food Source: Pharmacological Potential, Anti-Inflammatory Actions and Related Molecular Mechanisms.

Cordyceps militaris (C. militaris) is a medicinal mushroom possessing a variety of biofunctionalities. It has several biologically important components such as polysaccharides and others. The diverse pharmacological potential of C. militaris has generated interest in reviewing the current scientific literature, with a particular focus on prevention and associated molecular mechanisms in inflammatory diseases. Due to rising global demand, research on C. militaris has continued to increase in recent years. C. militaris has shown the potential for inhibiting inflammation-related events, both in in vivo and in vitro experiments. Inflammation is a multifaceted biological process that contributes to the development and severity of diseases, including cancer, colitis, and allergies. These functions make C. militaris a suitable functional food for inhibiting inflammatory responses such as the regulation of proinflammatory cytokines. Therefore, on the basis of existing information, the current study provides insights towards the understanding of anti-inflammatory activity-related mechanisms. This article presents a foundation for clinical use, and analyzes the roadmap for future studies concerning the medical use of C. militaris and its constituents in the next generation of anti-inflammatory drugs.

Polarity Directed Appraisal of Pharmacological Potential and HPLC-DAD Based Phytochemical Profiling of Polygonum glabrum Willd.

The present study was designed to evaluate polarity-dependent extraction efficiency and pharmacological profiling of Polygonum glabrum Willd. Crude extracts of leaves, roots, stems, and seeds, prepared from solvents of varying polarities, were subjected to phytochemical, antioxidant, antibacterial, antifungal, antidiabetic, and cytotoxicity assays. Maximum extraction yield (20.0% w/w) was observed in the case of an acetone:methanol (AC:M) root extract. Distilled water:methanol (W:M) leaves extract showed maximum phenolic contents. Maximum flavonoid content and free radical scavenging potential were found in methanolic (M) seed extract. HPLC-DAD quantification displayed the manifestation of substantial quantities of quercetin, rutin, gallic acid, quercetin, catechin, and kaempferol in various extracts. The highest ascorbic acid equivalent total antioxidant capacity and reducing power potential was found in distilled water roots and W:M leaf extracts, respectively. Chloroform (C) seeds extract produced a maximum zone of inhibition against Salmonella typhimurium. Promising protein kinase inhibition and antifungal activity against Mucor sp. were demonstrated by C leaf extract. AC:M leaves extract exhibited significant cytotoxic capability against brine shrimp larvae and α-amylase inhibition. Present results suggest that the nature of pharmacological responses depends upon the polarity of extraction solvents and parts of the plant used. P. glabrum can be considered as a potential candidate for the isolation of bioactive compounds with profound therapeutic importance.