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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.

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.

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.

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.

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.

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.

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.

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.

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.

Withaferin A: From Ancient Remedy to Potential Drug Candidate.

Withaferin A (WA) is a pivotal withanolide that has conquered a conspicuous place in research, owning to its multidimensional biological properties. It is an abundant constituent in Withania somnifera Dunal. (Ashwagandha, WS) that is one of the prehistoric pivotal remedies in Ayurveda. This article reviews the literature about the pharmacological profile of WA with special emphasis on its anticancer aspect. We reviewed research publications concerning WA through four databases and provided a descriptive analysis of literature without statistical or qualitative analysis. WA has been found as an effective remedy with multifaceted mechanisms and a broad spectrum of pharmacological profiles. It has anticancer, anti-inflammatory, antiherpetic, antifibrotic, antiplatelet, profibrinolytic, immunosuppressive, antipigmentation, antileishmanial, and healing potentials. Evidence for wide pharmacological actions of WA has been established by both in vivo and in vitro studies. Further, the scientific literature accentuates the role of WA harboring a variable therapeutic spectrum for integrative cancer chemoprevention and cure. WA is a modern drug from traditional medicine that is necessary to be advanced to clinical trials for advocating its utility as a commercial drug.

Caralluma tuberculata N.E.Br Manifests Extraction Medium Reliant Disparity in Phytochemical and Pharmacological Analysis.

Solubility of phytoconstituents depends on the polarity of the extraction medium used, which might result in the different pharmacological responses of extracts. In line with this, ethnomedicinally important food plant (i.e., Caralluma tuberculata extracts) have been made in fourteen distinct solvent systems that were then analyzed phytochemically via total phenolic amount estimation, total flavonoid amount estimation, and HPLC detection and quantification of the selected polyphenols. Test extracts were then subjected to a battery of in vitro assays i.e., antioxidants (DDPH scavenging, antioxidant capacity, and reducing power estimation), antimicrobial (antibacterial, antifungal, and antileishmanial), cytotoxic (brine shrimps, THP-1 human leukemia cell lines and normal lymphocytes), and protein kinase inhibition assays. Maximum phenolic and flavonoid contents were computed in distilled water-acetone and acetone extracts (i.e., 16 ± 1 µg/mg extract and 8 ± 0.4/mg extract, respectively). HPLC-DAD quantified rutin (0.58 µg/mg extract) and gallic acid (0.4 µg/mg extract) in methanol-ethyl acetate and methanol extracts, respectively. Water-acetone extract exhibited the highest DPPH scavenging of 36 ± 1%. Total reducing potential of 76.0 ± 1 µg/mg extract was shown by ethanol chloroform while maximum total antioxidant capacity was depicted by the acetone extract (92.21 ± 0.70 µg/mg extract). Maximal antifungal effect against Mucor sp., antileishmanial, brine shrimp cytotoxicity, THP-1 cell line cytotoxicity, and protein kinase inhibitory activities were shown by ethyl acetate-methanol (MIC: 50 µg/disc), n-hexane (IC50: 120.8 ± 3.7 µg/mL), ethyl acetate (LD50: 29.94 ± 1.6 µg/mL), distilled water-acetone (IC50: 118 ± 3.4 µg/mL) and methanol-chloroform (ZOI: 19 ± 1 mm) extracts, respectively. Our findings show the dependency of phytochemicals and bioactivities on the polarity of the extraction solvent and our preliminary screening suggests the C. tuberculata extract formulations to be tested and used in different ailments, however, detailed studies remain necessary for corroboration with our results.

HPLC-DAD Based Polyphenolic Profiling and Evaluation of Pharmacological Attributes of Putranjiva roxburghii Wall.

The current study was intended to explore the phytochemical profiling and therapeutic activities of Putranjiva roxburghii Wall. Crude extracts of different plant parts were subjected to the determination of antioxidant, antimicrobial, antidiabetic, cytotoxic, and protein kinase inhibitory potential by using solvents of varying polarity ranges. Maximum phenolic content was notified in distilled water extracts of the stem (DW-S) and leaf (DW-L) while the highest flavonoid content was obtained in ethyl acetate leaf (EA-L) extract. HPLC-DAD analysis confirmed the presence of various polyphenols, quantified in the range of 0.02 ± 0.36 to 2.05 ± 0.18 µg/mg extract. Maximum DPPH scavenging activity was expressed by methanolic extract of the stem (MeOH-S). The highest antioxidant capacity and reducing power was shown by MeOH-S and leaf methanolic extract (MeOH-L), respectively. Proficient antibacterial activity was shown by EA-L extract against Bacillus subtilis and Escherichia coli. Remarkable α-amylase and α-glucosidase inhibition potential was expressed by ethyl acetate fruit (EA-F) and n-Hexane leaf (nH-L) extracts, respectively. In case of brine shrimp lethality assay, 41.67% of the extracts (LC50 < 50 µg/mL) were considered as extremely cytotoxic. The test extracts also showed mild antifungal and protein kinase inhibition activities. The present study explores the therapeutic potential of P. roxburghii and calls for subsequent studies to isolate new bioactive leads through bioactivity-guided isolation.

Uterine arterio-venous malformation, an uncommon life-threatening condition: a case report.

Uterine Arteriovenous Malformation is a rare gynaecological disorder which commonly presents with profuse vaginal bleeding. This case report presents a patient referred to the Military Hospital, Rawalpindi from Pakistan Aeronautical Complex Hospital Kamra, a peripheral secondary care hospital. Patient was diagnosed as a case of Uterine Arteriovenous Malformation at the Military Hospital and was successfully treated with uterine artery embolization..

Effect of oxytocin infusion on reducing blood loss during abdominal myomectomy: A randomized controlled trial.

OBJECTIVE: To assess oxytocin infusion efficacy in terms of mean blood loss in patients undergoing abdominal myomectomy. METHODS: The single-blind randomised control trial was conducted at the Obstetrics and Gynaecology Department of Military Hospital, Rawalpindi, Pakistan, July 15, 2017, to January 15, 2018, and comprised women with intramural fibroids of American Society of Anaesthesia class I and II who were candidates for elective abdominal myomectomy. The women were randomised into study and control groups. In the study group, an infusion of 30 units of oxytocin in 1000ml normal saline was given at the rate of 15 units/hour during surgery. In the control group, pure normal saline was given. The main outcome measure was intra-operative blood loss. Data was analysed using SPSS 21. RESULTS: Of the 60 women, there were 30(50%) in the study group with a mean age of 37.10±4.35 years, and 30(50%) in the control group with a mean age of 36.67±3.70 (p>0.05). Mean intra-operative blood loss in the study group was 409.67±181.29ml which was significantly lower than the control group 875.33±284.71 (p<0.05). The mean surgery time also showed statistically significant difference between the two groups (p<0.05). In the study group, 3(10%) patients required blood transfusion, while blood was transfused to 11(36.6%) patients in the control group (p=0.046). CONCLUSIONS: Oxytocin, when given as an infusion, was found to be effective in reducing blood loss during abdominal myomectomy.

Polarity directed optimization of phytochemical and in vitro biological potential of an indigenous folklore: Quercus dilatata Lindl. ex Royle.

BACKGROUND: Plants have served either as a natural templates for the development of new chemicals or a phytomedicine since antiquity. Therefore, the present study was aimed to appraise the polarity directed antioxidant, cytotoxic, protein kinase inhibitory, antileishmanial and glucose modulatory attributes of a Himalayan medicinal plant- Quercus dilatata. METHODS: Total phenolic and flavonoid contents were determined colorimetrically and various polyphenols were identified by RP-HPLC analysis. Brine shrimp lethality, SRB and MTT assays were employed to test cytotoxicity against Artemia salina and human cancer cell lines respectively. Antileishmanial activity was determined using standard MTT protocol. Glucose modulation was assessed by α-amylase inhibition assay while disc diffusion assay was used to establish protein kinase inhibitory and antifungal spectrum. RESULTS: Among 14 extracts of aerial parts, distilled water-acetone extract demonstrated maximum extract recovery (10.52% w/w), phenolic content (21.37 ± 0.21 µg GAE/mg dry weight (DW)), total antioxidant capacity (4.81 ± 0.98 µg AAE/mg DW) and reducing power potential (20.03 ± 2.4 µg/mg DW). On the other hand, Distilled water extract proficiently extracted flavonoid content (4.78 ± 0.51 µg QE/mg DW). RP-HPLC analysis revealed the presence of significant amounts of phenolic metabolites (0.049 to 15.336 µg/mg extract) including, pyrocatechol, gallic acid, catechin, chlorogenic acid, p-coumaric acid, ferulic acid and quercetin. Highest free radical scavenging capacity was found in Methanol-Ethyl acetate extract (IC50 8.1 ± 0.5 µg/ml). In the brine shrimp toxicity assay, most of the tested extracts (57%) showed high cytotoxicity. Among these, Chloroform-Methanol extract had highest cytotoxicity against THP-1 cell line (IC50 3.88 ± 0.53 µg/ml). About 50% of the extracts were found to be moderately antiproliferative against Hep G2 cell line. Methanol extract exhibited considerable protein kinase inhibitory activity against Streptomyces 85E strain (28 ± 0.35 mm bald phenotype at 100 µg/disc; MIC = 12.5 µg/ disc) while, Chloroform extract displayed maximum antidiabetic activity (α-amylase inhibition of 21.61 ± 1.53% at 200 µg/ml concentration). The highest antileishmanial potential was found in Ethyl acetate-Acetone extract (12.91 ± 0.02% at 100 µg/ml concentration), while, Q. dilatata extracts also showed a moderate antifungal activity. CONCLUSION: This study proposes that multiple-solvent system is a crucial variable to elucidate pharmacological potential of Q. dilatata and the results of the present findings prospects its potential as a resource for the discovery of novel anticancer, antidiabetic, antileishmanial and antioxidant agents.

Appraisal of phytochemical and in vitro biological attributes of an unexplored folklore: Rhus Punjabensis Stewart.

BACKGROUND: The role of plants for discovery of therapeutic potential accentuates the need to know their biological attributes. The present study aims to comprehend the biological attributes of Rhus punjabensis, an unexplored traditional medicinal plant. METHODS: Leaf and stem extracts of R. punjabensis prepared in 11 different organic solvents are evaluated for multimode antioxidant potential, total phenolic and flavonoid contents were determined through colorimetric assays, HPLC-DAD analysis was carried out for quantification of various polyphenols in extracts. Brine shrimp lethality, SRB and MTT assays were used to elucidate plant's cytotoxic and antileishmanial potentials. Disc diffusion assay was used to elucidate the protein kinase inhibitory, antibacterial and antifungal spectrum. RESULTS: Ethanol + ethyl acetate yielded maximum extract recovery from leaf (6.11 ± 1.09% w/w), total phenolic content (80.5 ± 2.18 µg GAE/mg extract) and reducing power potential (165.4 ± 2.29 µg AAE/mg extract). Maximum flavonoid content (30.50 ± 1.11 µg QE/mg extract) and highest DPPH based free radical scavenging activity (IC50 11.4 ± 2.07) was exhibited by the methanol + chloroform leaf extract. The methanol extract showed maximum total antioxidant capacity (74.5 ± 2.25 µg AAE/mg DW), protein kinase inhibitory (12.5 ± 1.10 bald phenotype at 100 µg/disc) and antifungal (MIC = 25 µg/disc against Aspergillus flavus) potential. Reverse phase HPLC-DAD based quantification reveals presence of gallic acid, apigenin, rutin and catechin in various extracts. Brine shrimp lethality assay demonstrated most extracts as highly cytotoxic (LC50 < 50 µg/mL) whereas chloroform extract of leaf demonstrated maximuminhibition against human leukemia cell line (IC50 7.80 ± 0.01 µg/mL). A significant activity against leishmanial promastigotes was demonstrated by n-hexane leaf extract (IC50 = 15.78 ± 0.15 µg/mL). A better antibacterial activity,by the extracts, against Gram positive strains as compared to Gram negative was observed. CONCLUSIONS: Results recommend multiple-solvent system as a critical factor to sumptuous the biological prospective of R. punjabensis and propose it to be a useful natural hub for the discovery of novel antioxidant, anticancer, antileishmanial and antimicrobial agents.

Polarity based characterization of biologically active extracts of Ajuga bracteosa Wall. ex Benth. and RP-HPLC analysis.

BACKGROUND: The concept of botanical therapeutics has revitalized due to wide importance of plant derived pharmaceuticals. Therefore, the ameliorative characteristics of Ajuga bracteosa were studied. METHODS: Total phenolic content, flavonoid content, antioxidant capacity, reducing power and free-radical scavenging activity were determined colorimetrically. Specific polyphenols were quantified by RP-HPLC analysis. Preliminary cytotoxicity was tested using brine shrimp lethality assay while antiproliferative activity against THP-1 and Hep-G2 cell lines was determined by MTT and SRB protocols respectively. Antileishmanial potential was assessed via MTT colorimetric method. To investigate antidiabetic prospect, α-amylase inhibition assay was adopted whereas disc diffusion method was used to detect likely protein kinase inhibitory, antibacterial and antifungal activities. RESULTS: Among fifteen different extracts, maximum total phenolic content (10.75 ± 0.70 µg GAE/mg DW), total reducing power (23.90 ± 0.70 µg AAE/mg DW) and total antioxidant capacity (11.30 ± 0.80 µg AAE/mg DW) were exhibited by methanol extract with superlative percent extract recovery (17.50 ± 0.80% w/w). Chloroform-methanol extract demonstrated maximum flavonoid content (4.10 ± 0.40 µg QE/mg DW) and ethanol extract exhibited greatest radical scavenging activity (IC50 14.40 ± 0.20 µg/ml). RP-HPLC based quantification confirmed polyphenols such as pyrocatechol, gallic acid, resorcinol, catechin, chlorogenic acid, caffeic acid, syringic acid, p-coumaric acid, ferulic acid, vanillic acid, coumarin, sinapinic acid, trans-cinnamic acid, rutin, quercetin and kaempferol. The brine shrimp lethality assay ranked 78.60% extracts as cytotoxic (LC50 ≤ 250 µg/ml) whereas significant THP-1 inhibition was shown by methanol-acetone extract (IC50 4.70 ± 0.43 µg/ml). The antiproliferative activity against Hep-G2 hepatoma cancer cell line was demonstrated by n-hexane, ethylacetate and methanol-distilled water (IC50 8.65-8.95 µg/ml) extracts. Methanol extract displayed prominent protein kinase inhibitory activity (MIC 12.5 µg/disc) while n-hexane extract revealed remarkable antileishmanial activity (IC50 4.69 ± 0.01 µg/ml). The antidiabetic potential was confirmed by n-hexane extract (44.70 ± 0.30% α-amylase inhibition at 200 µg/ml concentration) while a moderate antibacterial and antifungal activities were unveiled. CONCLUSION: The variation in biological spectrum resulted due to use of multiple solvent systems for extraction. We also deduce that the valuable information gathered can be utilized for discovery of anticancer, antileishmanial, antioxidant and antidiabetic bioactive lead candidates.

Antioxidant, anticancer and antibacterial potential of Zakhm-e-hayat rhizomes crude extract and fractions.

Bergenia ciliata (locally known as Zakhm-e-hayat; wound healer) is commonly employed for wound healing, curing diarrhea and vomiting, fever, cough and pulmonary affections. Local community uses this plant as tea decoction with table salt. B. ciliata crude extract and its fractions were subjected to antibacterial, antioxidant effects as well as determination of total flavonoids and phenolics, DNA damage and anticancerous activities following standard protocols. Increased percentage inhibition of free radical in DPPH assay as well as elevated phenolic and flavonoid contents revealed antioxidant potential of this potent herb. Ethyl acetate and aqueous extracts showed IC(50) of 0.7 and 0.3 mg/ml respectively, against H157 cell line. Antibacterial analysis showed MIC 0.4-10mg/ml for crude extract and fractions. The results obtained conclude that extracts of B. ciliata contain remedial latent and can be used as possible source for drug development by pharmaceutical industries.

Preeclampsia: A comprehensive review.

Preeclampsia (PE) is a life-threatening disease of pregnancy and a prominent cause of neonatal and maternal mortality and morbidity. PE affects approximately 5-10% of pregnancies worldwide, posing significant risks to perinatal and maternal health. It is characterized by a variety of interconnected pathological cascades contributing to the stimulation of intravascular inflammation, oxidative stress (OS), endothelial cell activation, and syncytiotrophoblast stress that converge on a common pathway, ultimately resulting in disease progression. The present study was designed and executed to review the existing scientific literature, specifically focusing on the etiology (gestational diabetes mellitus and maternal obesity, insulin resistance, metabolic syndrome, maternal infection, periodontal disease, altered microbiome, and genetics), clinical presentations (hypertension, blood disorders, proteinuria, hepatic dysfunction, renal dysfunction, pulmonary edema, cardiac dysfunction, fetal growth restrictions, and eclampsia), therapeutic clinical biomarkers (creatinine, albuminuria, and cystatin C) along with their associations and mechanisms in PE. In addition, this study provides insights into the potential of nanomedicines for targeting these mechanisms for PE management and treatment. Inflammation, OS, proteinuria, and an altered microbiome are prominent biomarkers associated with progression and PE-related pathogenesis. Understanding the molecular mechanisms, exploring suitable markers, targeted interventions, comprehensive screening, and holistic strategies are critical to decreasing the incidence of PE and promoting maternal-fetal well-being. The present study comprehensively reviewed the etiology, clinical presentations, therapeutic biomarkers, and preventive potential of nanomedicines in the treatment and management of PE.