Beneficial effect of 5-HT1b/1d agonist on Parkinson's disease by modulating glutamate and reducing deposition of α-synuclein.

The given investigation examined the neuroprotection role of 5-HT1b/1d agonist in reserpine induced Parkinson's disease (PD) in male Wistar rats. PD was induced in rats by reserpine at 5 mg/kg ip for 3 days and thereafter the rats were provided with the following treatments for 4 days, zolmitriptan (ZLM) group (30 mg/kg ip); STD group (levodopa + carbidopa, 200 + 5 mg/kg ip); ZLM + GA group (zolmitriptan, 30 mg/kg ip and glutamic acid, 1.5 mg/kg); ZLM + DX group (zolmitriptan, 30 mg/kg ip and dextromethorphan, 20 mg/kg ip). All the groups were then assessed for cognitive and motor functions at the end of the protocol. Moreover, oxidative stress parameters and histopathological changes were observed in rats of all treatment groups. Deposition of α-synuclein in the brain tissue was observed by silver staining. Data of this investigation revealed that motor and cognitive functions were improved in the ZLM-treated group compared with the negative control group, which was observed to be reversed in ZLM + GA group. Treatment with ZLM ameliorated oxidative stress and histopathological changes in the brain tissue of PD rats. Further, ZLM reduced the deposition of α-synuclein in PD rats, which reversed in ZLM + GA-treated group. This study concludes by stating that 5-HT1b/1d agonist can prevent neurodegeneration and reduce oxidative stress in PD rats. The probable underlying mechanism of such an effect of 5-HT1b/1d agonist could be by regulating the deposition of α-synuclein and reducing the expression of NMDA receptor.

Surface Passivation Method for the Super-repellence of Aqueous Macromolecular Condensates.

Solutions of macromolecules can undergo liquid-liquid phase separation to form droplets with ultralow surface tension. Droplets with such low surface tension wet and spread over common surfaces such as test tubes and microscope slides, complicating in vitro experiments. The development of a universal super-repellent surface for macromolecular droplets has remained elusive because their ultralow surface tension requires low surface energies. Furthermore, the nonwetting of droplets containing proteins poses additional challenges because the surface must remain inert to a wide range of chemistries presented by the various amino acid side chains at the droplet surface. Here, we present a method to coat microscope slides with a thin transparent hydrogel that exhibits complete dewetting (contact angles θ ≈ 180°) and minimal pinning of phase-separated droplets in aqueous solution. The hydrogel is based on a swollen matrix of chemically cross-linked polyethylene glycol diacrylate of molecular weight 12 kDa (PEGDA), and can be prepared with basic chemistry laboratory equipment. The PEGDA hydrogel is a powerful tool for in vitro studies of weak interactions, dynamics, and the internal organization of phase-separated droplets in aqueous solutions.

Protective effect of vanillin on the management of cecal ligation and puncture induced sepsis rat model.

Present investigation evaluates the protective effect of vanillin against sepsis. Sepsis was induced by cecal ligation and puncture (CLP) in rat and vanillin was administered at dose of 100 and 200 mg/kg p.o. for five days after induction of sepsis. Effect of vanillin was observed on the percentage of survival, body weight and food intake were determined in CLP induced sepsis rats. Level of liver enzymes in the serum and organ weight was also observed in vanillin treated CLP induced rats. Moreover, histopathological changes were also observed in liver and lung tissue of hematoxylin and eosin (H&E) staining. There was significant improvement in bodyweight and food intake in vanillin treated group than negative control group after the sepsis induction. Moreover, vanillin improves the percentage of survival rate and reduces the level of liver enzymes and spleen weight in CLP induced sepsis rat. It also improves the level of glutathione (GSH) compared to negative control group. In conclusion, data of investigation reveals that vanillin ameliorates the survival rate and oxidative stress in CLP induced sepsis rat model.

Intravenous ketamine in gynaecological surgeries reduces pain score and opioid consumption.

OBJECTIVE: To assess the effect of intravenous ketamine on postoperative pain control, opioid consumption, and the incidence of postoperative adverse events in gynaecological surgeries. METHODS: The systematic review and meta-analysis were conducted in July 2020 and the search was repeated in July 2021 to ensure accuracy. The review was registered with the International Prospective Register of Systematic Reviews (PROSPERO) as ID-CRD42020188637 in July 2020. The search, done on online databases Medline and Science Direct, comprised studies on patients who underwent general anaesthesia for gynaecological surgeries and received intravenous ketamine intraoperatively, and the findings included opioid consumption, postoperative pain control, and associated side-effects. RESULTS: Of the 79 randomised controlled trials found, 9 (11.4%) were subjected to meta-analysis. The use of intravenous ketamine reduced pain score at 2h (p=0.003) and 24h (p=0.002) postoperatively in gynaecological surgeries. In laparoscopic gynaecological surgeries, lower pain scores were reported at 1h (p=0.01) and 2h (p=0.002) postoperatively. Lower pain scores were reported at 24h postoperatively in open gynaecological surgeries (p=0.002). Intravenous ketamine increased the time to first-request analgesia postoperatively (p=0.03), and reduced postoperative 24h opioid consumption (p=0.002). CONCLUSIONS: The use of intravenous ketamine significantly reduced postoperative pain at 2h and 24h after gynaecological surgeries and at 1h and 2h after laparoscopic gynaecological surgeries.

Enhancing the Refractive Index of Polymers with a Plant-Based Pigment.

Polymers are essential components of many nanostructured materials. However, the refractive indices of common polymers fall in a relatively narrow range between 1.4 and 1.6. Here, it is demonstrated that loading commercially-available polymers with large concentrations of a plant-based pigment can effectively enhance their refractive index. For polystyrene (PS) loaded with 67 w/w% ß-carotene (BC), a peak value of 2.2 near the absorption edge at 531 nm is achieved, while maintaining values above 1.75 across longer wavelengths of the visible spectrum. Despite high pigment loadings, this blend maintains the thermoforming ability of PS, and BC remains molecularly dispersed. Similar results are demonstrated for the plant-derived polymer ethyl cellulose (EC). Since the refractive index enhancement is intimately connected to the introduction of strong absorption, it is best suited to applications where light travels short distances through the material, such as reflectors and nanophotonic systems. Enhanced reflectance from films is experimentally demonstrated, as large as sevenfold for EC at selected wavelengths. Theoretical calculations highlight that this simple strategy can significantly increase light scattering by nanoparticles and enhance the performance of Bragg reflectors.

Potential Inhibitors for SARS-CoV-2 and Functional Food Components as Nutritional Supplement for COVID-19: A Review.

The severe acute respiratory syndrome is a viral respiratory infection and commonly called as COVID-19, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It widely transmitted through direct or indirect contact. Currently, no specific treatment against SARS-CoV-2 are available; only prevention and supportive strategy are the preventive measures. The present review emphasizes the latest research related to COVID-19 and SARS-CoV-2 virus as well as the current status of potential inhibitors identified. Recent interest in SARS-CoV-2 has focused on transmission, symptoms, structure, and its structural proteins that exhibit promising therapeutics targets for rapid identification of potential inhibitors. The quick identification of potential inhibitors and immune-boosting functional food ingredients are crucial to combat this pandemic disease. We also tried to give an overview of the functional food components as a nutritional supplement, which helps in boosting our immune system and could be useful in preventing the COVID-19 and/or to improve the outcome during therapy.

One-Step Ring Opening Metathesis Block-Like Copolymers and their Compositional Analysis by a Novel Retardation Technique.

Using a one-step synthetic route for block copolymers avoids the repeated addition of monomers to the polymerization mixture, which can easily lead to contamination and, therefore, to the unwanted termination of chain growth. For this purpose, monomers (M1-M5) with different steric hindrances and different propagation rates are explored. Copolymerization of M1 (propagating rapidly) with M2 (propagating slowly), M1 with M3 (propagating extremely slowly) and M4 (propagating rapidly) with M5 (propagating slowly) yielded diblock-like copolymers using Grubbs' first (G1) or third generation catalyst (G3). The monomer consumption was followed by 1 H NMR spectroscopy, which revealed vastly different reactivity ratios for M1 and M2. In the case of M1 and M3, we observed the highest difference in reactivity ratios (r1 =324 and r2 =0.003) ever reported for a copolymerization method. A triblock-like copolymer was also synthesized using G3 by first allowing the consumption of the mixture of M1 and M2 and then adding M1 again. In addition, in order to measure the fast reaction rates of the G3 catalyst with M1, we report a novel retardation technique based on an unusual reversible G3 Fischer-carbene to G3 benzylidene/alkylidene transformation.

Catalytic Living Ring Opening Metathesis Polymerisation: The Importance of Ring Strain in Chain Transfer Agents.

A recently developed catalytic living ring opening metathesis polymerisation (ROMP) was investigated using a series of reversible chain transfer agents (CTA) carrying either cyclopentene or cyclohexene rings, differing only in ring strain. All cyclopentene derivatives examined showed significantly faster reaction rates than the corresponding cyclohexene derivatives. This resulted in lower molecular weight dispersities and better control of the molecular weight for the cyclopentene compared to the cyclohexene CTAs. Both Grubbs' second and third generation catalysts could be employed in catalytic living ROMP using cyclopentene CTA derivatives. The kinetics of different CTAs were studied, block copolymers were synthesised and residual ruthenium quantified by ICP-OES. All polymers were fully characterised by NMR, GPC and MALDI-ToF mass spectrometry. The new cyclopentene CTAs are readily synthesised in a few straightforward steps and provide faster reaction kinetics than all previously reported reversible CTAs.

Heterotelechelic Polymers by Ring-Opening Metathesis and Regioselective Chain Transfer.

Heterotelechelic polymers were synthesized by a kinetic telechelic ring-opening metathesis polymerization method relying on the regioselective cross-metathesis of the propagating Grubbs' first-generation catalyst with cinnamyl alcohol derivatives. This procedure allowed the synthesis of hetero-bis-end-functional polymers in a one-pot setup. The molecular weight of the polymers could be controlled by varying the ratio between cinnamyl alcohol derivatives and monomer. The end functional groups can be changed using different aromatically substituted cinnamyl alcohol derivatives. Different monomers were investigated and the presence of the functional groups was shown by NMR spectroscopy and MALDI-ToF mass spectrometry. Labeling experiments with dyes were conducted to demonstrate the orthogonal addressability of both chain ends of the heterotelechelic polymers obtained.

In silico interaction of methyl isocyanate with immune protein responsible for Mycobacterium tuberculosis infection using molecular docking.

This article reports in silico analysis of methyl isocyanate (MIC) on different key immune proteins against Mycobacterium tuberculosis. The analysis shows that MIC is released in the Bhopal gas tragedy in 1984, which is highly toxic and extremely hazardous to human health. In this study, we have selected immune proteins to perform molecular docking with the help of Autodock 4.0. Results show that the CD40 ligand and alpha5beta1 integrin have higher inhibition compared to plasminogen activator urokinase, human glutathione synthetase, mitogen-activated protein kinase (P38 MAPK 14), surfactant protein-B, -D (SP-D), and pulmonary SP-D. MIC interacted with His-125, Try-146 residue of CD40 ligand and Ala-149, and Arg-152 residue of alpha5beta1 integrin and affects the proteins functioning by binding on their active sites. These inhibitory conformations were energetically and statistically favored and supported the evidence from wet laboratory experiments reported in the literature. We can conclude that MIC directly or indirectly affects these proteins, which shows that survivals of the disaster suffer from the diseases like tuberculosis infection and lung cancer.

Tandem Ring-Opening-Ring-Closing Metathesis for Functional Metathesis Catalysts.

Use of a tandem ring-opening-ring-closing metathesis (RORCM) strategy for the synthesis of functional metathesis catalysts is reported. Ring opening of 7-substituted norbornenes and subsequent ring-closing metathesis forming a thermodynamically stable 6-membered ring lead to a very efficient synthesis of new catalysts from commercially available Grubbs' catalysts. Hydroxy functionalized Grubbs' first- as well as third-generation catalysts have been synthesized. Mechanistic studies have been performed to elucidate the order of attack of the olefinic bonds. This strategy was also used to synthesize the ruthenium methylidene complex.

Effect of Intravenous Dexmedetomidine Before Extubation on Emergence Delirium after Nasal Surgeries.

OBJECTIVE: To investigate the role of single dose of dexmedetomidine (0.5 mcg/kg) in reducing the incidence and severity of postoperative emergence delirium (EmD). STUDY DESIGN: A randomised controlled trial. Place and Duration of the Study: Department of Anaesthesia, Security Forces Hospital, Riyadh, Saudi Arabia, from 1st December 2022 to 30th March 2023. METHODOLOGY: Patients, aged between 18-65 years, with ASA 1-3 scheduled to undergo nasal surgeries under general anaesthesia, were inducted in the study. Exclusion criteria were patient refusal, later request for removal from the study, inability to give consent, known allergy to dexmedetomidine, body mass index (BMI) more than 35, history of obstructive sleep apnoea, history of psychiatric illness, pregnancy, and presence of liver and renal diseases. The primary outcome measure of the study was the incidence of emergence delirium in the postoperative period. RESULTS: The frequency of EmD after nasal surgery was 52.38% in the control group compared to 14.28% in the dexmedetomidine group (p = 0.01). Pain scores were not statistically different between the two groups. The duration of post anaesthesia care unit (PACU) stay was significantly lesser in dexmedetomidine group (p <0.001). The satisfaction score on the visual analogue scale (VAS) was also found to be higher in patients who received intravenous dexmedetomidine (p <0.001). CONCLUSION: The use of single dose dexmedetomidine before extubation in nasal surgeries reduces the EmD and improves patient satisfaction. KEY WORDS: Dexmedetomidine, Emergence delirium, Nasal surgery, Opioid consumption, Pain control.

Effect of Dexmedetomidine Addition in Erector Spinae Plane Block on Opioid Consumption after Lumbar Spine Surgery.

OBJECTIVE: To investigate the efficacy of adding 0.5 micrograms/kg of dexmedetomidine to 0.2% ropivacaine in erector spinae plane block in terms of 24-hour opioid consumption after lumbar spine surgeries. STUDY DESIGN: A randomised controlled trial. Place and Duration of the Study: The Security Forces Hospital, Riyadh, Saudi Arabia, from 30th November 2022 to 30th March 2023. METHODOLOGY: Patients aged between 18-70 years, ASA 1-3 who were booked to undergo lumbar spine surgeries under general anaesthesia were inducted. Patients in the intervention group received erector spinae plane block (ESPB). Exclusion criteria were patient refusal, inability to give consent, patients with contraindications to regional anaesthesia, known allergy to study medications, inability to use patient-controlled analgesia (PCA), psychiatric disorders or patients using any psychiatric medications. The primary outcome measure of the study was 24-hour opioid consumption. RESULTS: The numeric rating scale (NRS) pain scores were significantly decreased in the ESPB-D group at 30 minutes (p = 0.042), at 1 hour (p = 0.018), at 2 hours (p = 0.044), at 12 hours (p = 0.039), at 18 hours (p = 0.011), and at 24 hours (p = 0.020). Intraoperative use of remifentanil was also significantly lower in the ESPB-D group (p <0.01). ESPB using dexmedetomidine also reduced opioid consumption over a period of 24 hours (p <0.01). Median patient satisfaction score and median ease of mobility were also significantly better in the ESPB-D group. CONCLUSION: Addition of dexmedetomidine in erector spinae plane block reduced pain scores and intraoperative and postoperative opioid consumption after lumbar spine surgery. KEY WORDS: Dexmedetomidine, Erector spinae plane block, Lumbar spine surgery, Opioid consumption, Pain control.

Theranostics: a multifaceted approach utilizing nano-biomaterials.

Biomaterials play a vital role in targeting therapeutics. Over the years, several biomaterials have gained wide attention in the treatment and diagnosis of diseases. Scientists are trying to make more personalized treatments for different diseases, as well as discovering novel single agents that can be used for prognosis, medication administration, and keeping track of how a treatment works. Theranostics based on nano-biomaterials have higher sensitivity and specificity for disease management than conventional techniques. This review provides a concise overview of various biomaterials, including carbon-based materials like fullerenes, graphene, carbon nanotubes (CNTs), and carbon nanofibers, and their involvement in theranostics of different diseases. In addition, the involvement of imaging techniques for theranostics applications was overviewed. Theranostics is an emerging strategy that has great potential for enhancing the accuracy and efficacy of medicinal interventions. Despite the presence of obstacles such as disease heterogeneity, toxicity, reproducibility, uniformity, upscaling production, and regulatory hurdles, the field of medical research and development has great promise due to its ability to provide patients with personalised care, facilitate early identification, and enable focused treatment.

Geraniol reverses obesity by improving conversion of WAT to BAT in high fat diet induced obese rats by inhibiting HMGCoA reductase.

OBJECTIVES: Present report evaluates the protective effect of geraniol on high fat diet (HFD) induced obesity in rats and also determines the molecular mechanism of it. METHODS: Rats were induced with obesity with administration of HFD for four weeks and geraniol 200 and 400 mg/kg p.o. was administered for the next four week in the respective groups. Blood glucose and oral glucose tolerance test (OGTT), lipid profile was estimated in the geraniol treated HFD induced obesity in rats. Moreover, docking study was performed to determine the specific mechanism of geraniol by targeting HMG-CoE A reductase (in silico). RESULTS: There was significant increase in body weight and amelioration in altered serum glucose and lipid profile were observed in the geraniol treated group than negative control group. Weight of organs and adipose tissue isolated from different regions of the body was reduced in geraniol treated group than negative control. Moreover, geraniol interact with HMG-CoA reductase having binding energy -5.13. CONCLUSIONS: In conclusion, data of the report reveals that geraniol reduces obesity by promoting the conversion of white adipose tissue (WAT) to brown adipose tissue (BAT), as it interacts with HMG-CoA reductase in HFD induced obesity in rats.

A Single Functionalization Agent for Heterotelechelic ROMP Polymers.

Heterotelechelic polymers are an important class of materials finding applications in bioconjugation, imaging, sensing, and synthesis of organic/inorganic hybrid systems with interesting features. However, the synthesis of such polymers is challenging. Here, we report a mechanistically unique and most efficient method based on a single functionalization agent to prepare heterotelechelic polymers by a ring-opening metathesis polymerization. Different functionalization agents can be synthesized in one simple step from inexpensive commercial starting materials. The functionalization agents initially generate a functional initiator from commercial Grubbs' first-generation ruthenium benzylidene catalyst. During this process, a functional dihydrofuran derivative is produced. After functional initiation and propagation of a suitable monomer, the dihydrofuran derivative functionally terminates the polymerization yielding a primary alcohol-terminated heterotelechelic polymer. Molecular weight control is achieved by varying the ratio between monomer and Grubbs' first-generation catalyst. This method may emerge as a popular choice to prepare heterotelechelic polymers due to its simplicity and efficiency.

Recent advancements in the field of flexible/wearable enzyme fuel cells.

This review article focusses on new advances in the field of enzyme fuel cells (EFCs), especially, on flexible materials which can be used to make flexible EFCs for wearable devices, three-dimensional (3D) printed structures to prepare electrodes for EFCs and micro/nano electromechanical structures (MEMS/NEMS) to fabricate micro-EFCs. Particular attention is given to newly developed approaches to obtain efficient electrodes for harvesting energy via EFCs. This review article explains the various attributes of these recently developing technologies and their ability to mitigate the energy requirements of flexible/wearable bioelectronic devices. Besides discussing key milestones achieved, this perspective review article also emphasizes the main hurdles that are currently impeding the realization of flexible/wearable EFCs. We have also emphasized on the major hurdles related to the flexible materials required to fabricate wearable EFCs, suitable 3D printing techniques required, and MEMS and NEMS to fabricate micro-EFCs. In all the recently developed techniques, there are some common issues like stability, low power output, mechanical strength and flexibility. This review article also provides various routes to mitigate these issues. The main aim of this perspective article is to develop curiosity among the researchers of various fields to team up in order to address the huge challenges that restrict the real-world application of flexible/wearable EFCs. Such collaboration is important to harness the full potential of EFCs. It is requested to read this review article with supporting information to get the complete essence.

Can ACS-NSQIP score be used to predict postoperative mortality in Saudi population?

Background: Various scoring systems help in classifying the patient's risk preoperatively and hence to decide the best available treatment option. ACS-NSQIP score has been introduced in clinical practice for few years. This study was done to find out whether there is any difference between predicted mortality from ACS-NSQIP score and observed mortality in Saudi population. Methods: This prospective observational study was conducted at Security Forces Hospital, Riyadh, Kingdom of Saudi Arabia. We included patients undergoing elective and emergency surgical procedures in our hospital. Thirty days mortality data was collected and then observed to expected (O/E) mortality ratio was calculated. The sample size for our study was nine hundred and three (903) patients. Results: The mean ACS-NSQIP mortality risk score (%) for the study was 0.49. Expected number of mortalities was 4.42 while observed mortalities were 11, yielding an O/E ratio of 2.48 (p-value 0.000). We did not find a significant difference between expected and observed mortalities except for ASA class 3 and 4 patients where expected numbers of mortalities were lower than observed (p-value < 0.05). Conclusion: ACS-NSQIP can be reliably used for postoperative mortality prediction especially in lower risk groups.

Cascade Ring-Opening/Ring-Closing Metathesis Polymerization of a Monomer Containing a Norbornene and a Cyclohexene Ring.

Norbornene is polymerized extremely fast when reacted with Grubbs' first (G1) or third generation catalyst (G3) because of its very high ring strain energy. Cyclohexene, on the other hand, cannot be polymerized using G1 or G3 due to its very low ring strain energy. Subsequently, the sequence-selective polymerization of these two monomers is extremely challenging. A sequence-selective cascade ring-opening/ring-closing metathesis polymerization of the monomer M containing both the norbornene and the cyclohexene ring using G1 or G3 is reported. The polymer structure was analyzed by 1H NMR, 1H-1H COSY, and 1H-1H ROESY spectroscopy and MALDI-ToF mass spectrometry. Polymers with moderate molecular weight dispersities and good molecular weight control were achieved by varying the ratio between monomer M and G1.

In silico identification of promising inhibitor against RNA-dependent RNA polymerase target of SARS-CoV-2.

The severe acute respiratory syndrome is a viral respiratory disease recognised as COVID-19, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Formerly, no precise remedies are available, and many studies regarding COVID-19 prevention and treatment are under development. Several targets for the design of drugs are identified, and studies are in headway to explore the potential target. RNA-dependent RNA polymerase (RdRp) protein identified as a promising target against SARS-CoV-2 infection for the drug design due to its significant role in viral replication. The present study focuses on identifying the binding effect of previously known RdRp inhibitors with RdRp of SARS-CoV-2 using molecular docking and molecular dynamics simulation approaches. Molecular docking and binding free energy calculations against RdRp enzyme identified suramin as a potential compound that showed the highest docking score of -7.83 Kcal/mole and binding energy of -80.83 Kcal/mole as a comparison to other compounds. Further, molecular dynamics simulation studies were moreover showed the stable binding behaviour of suramin docked complex in the protein active site. Thus, the study concludes that suramin might be helpful as a potential inhibitor against RNA-dependent RNA polymerase of SRAS-CoV-2. However, further investigation is needed to assess the possible effect of inhibitors on RdRp through in vitro and in vivo experiments.