Influence of photoperiod variations on the mRNA expression pattern of melatonin bio-synthesizing enzyme genes in the pineal organ and retina: A study in relation to the serum melatonin profile in the tropical carp Catla catla.

Surface-dwelling C. catla were exposed to different photoperiods (8L:16D, 12L:12D, 12D:12L and 16L:8D) and the mRNA level profile of enzymes involved in melatonin synthesis was evaluated in the pineal gland and retina. Furthermore, a comparative analysis of the serum melatonin profile with the mRNA level was also performed. The results indicated diurnal variations in the transcripts of tph1, aanat and hiomt in the pineal organ and retina, and these variations change with the change in lighting regime. The serum melatonin profile showed rhythmicity in the natural photoperiod, but the serum melatonin level increased proportionally with increasing daylength. In short photoperiods, the peak value (though lower than in long photoperiods) of melatonin maintains a longer duration in serum. Moreover, the comparative analysis revealed a similar profile of mRNA of pineal aanat1 and aanat2 with serum melatonin under the same lighting conditions. This indicates that serum melatonin is produced by the pineal gland. Our results specify the importance of day length and the timing of onset or offset of the dark for maintaining the oscillating levels of serum melatonin and mRNA levels of melatonin biosynthesizing enzyme genes in the pineal organ and retina as well. The findings in this study highlight the distinctive pattern of mRNA levels in the pineal organ and retina under different photoperiods. The pineal melatonin biosynthesizing enzyme genes showed a similar pattern with serum melatonin levels while the retinal genes changed dramatically with photoperiod. We also revealed a light-dependent transcriptional regulation of pineal aanat genes in C. catla. Moreover, our results suggest that ALAN and skyglow can influence the levels of serum melatonin and its biosynthesis, resulting in desynchronization of the entire biological clock as well as the overall physiology of the animal.

Melatonin biosynthesizing enzyme genes and clock genes in ovary and whole brain of zebrafish (Danio rerio): Differential expression and a possible interplay.

The present study on zebrafish (Danio rerio) is the first attempt to demonstrate the circadian mRNA expression of melatonin biosynthesizing enzyme genes (Tph1a, Aanat1, Aanat2 and Hiomt) and clock associated genes (Bmal1a, Clock1a, Per1b, Per2 and Cry2a) in the ovary with a comparison to whole brain in normal (LD=12h L:12h D) and altered photic conditions (continuous dark, DD; continuous light, LL). Moreover, the present study also confirmed the ability of zebrafish ovary to biosynthesize melatonin both in vivo and in vitro with a significant difference at day and night. qRT-PCR analysis of genes revealed a dark acrophase of Aanat2 in both organs while Tph1 is in whole brain in LD condition. On the contrary, Bmal1a and Clock1a giving their peak in light, thereby showing a negative correlation with Tph1a and Aanat2. In LD-ovary, the acrophase of Tph1a, Bmal1a and Clock1a is in light and thus display a positive correlation. This trend of relationship in respect to Tph1a is not changing in altered photic conditions in both organs (except in DD-ovary). On the other hand this association for Aanat2 is varying in ovary under altered photic conditions but only in DD-whole brain. Both in LD and LL the expression of Aanat2 in brain presenting an opposite acrophase with both Bmal1a and Clock1a of ovary and consequently displaying a strong negative correlation among them. Interestingly, all ovarian clock associated genes become totally arrhythmic in DD, representing a loss of correlation between the melatonin synthesizing genes in brain and clock associated genes in ovary. The result is also indicating the formation of two heterodimers namely Clock1a:Bmal1a and Per2:Cry2a in the functioning of clock genes in both organs, irrespective of photic conditions, as they are exhibiting a strong significant positive correlation. Collectively, our data suggest that ovary of zebrafish is working as peripheral oscillator having its own melatonin biosynthesizing machinery and signifying a possible correlation with central oscillating system in various photic conditions.

Effects of Botulinum Toxin-A for Spasticity and Nociceptive Pain in Individuals with Spinal Cord Injury: A Systematic Review and Meta-Analysis.

We conducted a systematic review and meta-analysis to examine the protective effects of botulinum toxin-A (Botox-A) on spasticity and nociceptive pain in individuals with spinal cord injuries (SCIs). PubMed, Embase, and Cochrane Library databases were searched from inception to July 2023. The primary outcome of interest was spasticity and nociceptive pain. We pooled the available data using the generic inverse variance method, and we used a fixed-effect/random-effects model. We then calculated standardized mean difference (SMD) and 95% confidence intervals (95% CIs) to estimate the effect size. A total of fourteen studies meeting the inclusion criteria comprised two randomized controlled trials, five pre-post studies, and seven case reports. Across the various study designs, the majority of trials were assessed to have fair to high quality. The meta-analysis shows that Botox-A significantly decreased spasticity (SMD, -1.73; 95% CI, -2.51 to -0.95; p<0.0001, I2=48%) and nociceptive pain (SMD, -1.79; 95% CI, -2.67 to -0.91; p<0.0001, I2=0%) in SCI patients. Furthermore, Botox-A intervention improved motor function, activities of daily living (ADL), and quality of life. Our study suggests that Botox-A may alleviate spasticity and nociceptive pain in SCI patients. Moreover, the observed improvements in motor function, ADL, and overall quality of life following Botox-A intervention underscore its pivotal role in enhancing patient outcomes.

Effects of isoflurane and xylazine on inducing cerebral ischemia by the model of middle cerebral artery occlusion in mice.

Preclinical ischemic stroke studies extensively utilize the intraluminal suture method of middle cerebral artery occlusion (MCAo). General anesthesia administration is an essential step for MCAo, but anesthetic agents can lead to adverse effects causing death and making a considerable impact on inducing cerebral ischemia. The purpose of this study was to comparatively assess the effect of isoflurane and xylazine on transient cerebral ischemia in a mouse model of MCAo. Twenty animals were randomly divided into four groups: sham group (no MCAo), control group (MCAo under isoflurane, no agent till reperfusion), isoflurane group (MCAo under isoflurane continued till reperfusion), xylazine group (MCAo under isoflurane, and administration of xylazine till reperfusion). The survival rate, brain infarct volume, and neurologic deficits were studied to assess the effect of isoflurane and xylazine on the stroke model. Our results showed that the body weight showed statistically significant change before and 24 h after surgery in the control and Isoflurane groups, but no difference in the Xylazine group. Also, the survival rate, brain infarct volume, and neurologic deficits were slightly reduced in the isoflurane group at 24 h after reperfusion injury. However, the xylazine and control groups showed similar BIV and neurologic deficits. Interestingly, a high survival rate was observed in the xylazine group. Our results indicate that the modified method of inhalation anesthetics combined with xylazine can reduce the risk of mortality and develop a reproducible MCAo model with predictable brain ischemia. In addition, extended isoflurane anesthesia after MCAo is associated with the risk of mortality.

Novel Capturer-Catalyst Microreactor System with a Polypyrrole/Metal Nanoparticle Composite Incorporated in the Porous Honeycomb-Patterned Film.

A composite of polypyrrole/metal nanoparticles (PPy/MNPs) was selectively incorporated into the pores of a honeycomb-patterned porous polycaprolactone polymer film to fabricate a novel capturer-catalyst microreactor system. This fabrication involved a modified breath figure method, where the polymer solution containing metal ions as an oxidizing agent was cast under humid conditions along with the pyrrole monomer through an interfacial reaction in a one-step in situ process. The higher hydrophilicity of the metal ions compared to the polymer solution led to their self-assembly around the pore surface, resulting in the selective incorporation of the PPy/MNP composite into the porous film. Copper (Cu), silver (Ag), and gold (Au) were used for the PPy/MNP fabrication. Various methods characterized the fabricated film. Strong catalytic degradations of methylene blue and methyl orange were obtained with PCL-PPy/MNPs. Recycling experiments showed no loss of activity even after five cycles of recycling. Comparative analysis of PCL-PPy, PCL-MNP, and PCL-PPy/MNP results indicated the synergistic action of PPy and MNPs in dye degradation. High-performance liquid chromatography and mass spectroscopy analyses confirmed dye degradation after treatment with a fabricated microreactor. PPy might have acted as a capturer of the dye molecule and MNPs as a catalyst, thereby enhancing the efficiency of dye degradation. Additionally, the PCL-PPy/Cu composite exhibited strong antimicrobial properties against Gram-positive (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli) with no cytotoxicity as measured by the MTT assay. Therefore, the fabricated microreactor film has promising applications in various fields.

Effect of Daily Coffee Consumption on the Risk of Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Alzheimer's disease (AD) is a highly prevalent neurodegenerative disorder that affects millions of individuals globally. The identification of the lifestyle factors that potentially help prevent or postpone disease onset is of interest to the researchers. Although the study results are inconsistent, one such factor that has been extensively studied is coffee consumption. Therefore, this meta-analysis primarily aimed to investigate the effects of coffee consumption on the risk of AD. Pubmed, Embase, and Web of Science (Only Writing Web of Science is Fine) databases were searched for relevant studies with the keywords in various combinations, including "coffee", "caffeine", and "Alzheimer's disease". This meta-analysis included 11 studies. The relative risk (RR) with 95% confidence intervals (CI) was calculated to estimate the effect size. The study used the restricted maximum-likelihood method for a generic-inverse-variance analysis with random-effect (when heterogeneity, I2 > 50%) or fixed-effect (when heterogeneity, I2 < 50%) modeling. The study protocol has been registered at International Prospective Register of Systematic Reviews (CRD42023429016). Individuals that regularly consumed 1-2 cups and 2-4 cups coffee/day demonstrated a significantly lower risk of developing AD (1-2 cups/day: RR = 0.68, 95% CI = 0.54 to 0.83, I2 = 50.99%, p = 0.00 [the software used for analysis, shows the results of p value like this (0.00), I prefer not to change this as this is also fine]; 2-4 cups/day: RR = 0.79, 95% CI = 0.56 to 1.02, I2 = 71.79%, p = 0.00). However, individuals who consumed > 4 cups/day demonstrated an increased risk of developing AD (RR = 1.04, 95% CI = 0.91 to 1.17, I2 = 0.00%, p = 0.00). This meta-analysis indicates that limited (1-4 cups/day) daily coffee consumption reduces the risk of AD, whereas excessive consumption (> 4 cups/day) might increase the risk.

Phytochemical mediated modulation of COX-3 and NFκB for the management and treatment of arthritis.

In this study, we investigated whether zerumbone (ZBN), ellagic acid (ELA) and quercetin (QCT), the plant-derived components, can modulate the role of COX-3 or cytokines liable in arthritic disorder. Initially, the effect of ZBN, ELA, and QCT on inflammatory process was investigated using in-vitro models. In-silico docking and molecular dynamics study of these molecules with respective targets also corroborate with in-vitro studies. Further, the in-vivo anti-arthritic potential of these molecules in Complete Freund's adjuvant (CFA)-induced arthritic rats was confirmed. CFA increases in TNF-α and IL-1ß levels in the arthritic control animals were significantly (***p < 0.001) attenuated in the ZBN- and ELA-treated animals. CFA-induced attenuation in IL-10 levels recovered under treatment. Moreover, ELA attenuated CFA-induced upregulation of COX-3 and ZBN downregulated CFA-triggered NFκB expression in arthritic animals. The bonding patterns of zerumbone in the catalytic sites of targets provide a useful hint in designing and developing suitable derivatives that can be used as a potential drug. To our best knowledge, the first time we are reporting the role of COX-3 in the treatment of arthritic disorders which could provide a novel therapeutic approach for the treatment of inflammatory disorders.

Quantification of Neuronal Cell-Released Hydrogen Peroxide Using 3D Mesoporous Copper-Enriched Prussian Blue Microcubes Nanozymes: A Colorimetric Approach in Real Time and Anticancer Effect.

Despite the effectiveness and selectivity of natural enzymes, their instability has paved the way for developing nanozymes with high peroxidase activity using a straightforward technique, thereby expanding their potential for multifunctional applications. Herein, meso-copper-Prussian blue microcubes (Meso-Cu-PBMCs) nanozymes were successfully prepared via a cost-effective hydrothermal route. It was found that the Cu-PBMCs nanozymes, with three-dimensional (3D) mesoporous cubic morphologies, exhibited an excellent peroxidase-like property. Based on the high affinity of Meso-Cu-PBMCs toward H2O2 (Km = 0.226 µM) and TMB (Km = 0.407 mM), a colorimetric sensor for in situ H2O2 detection was constructed. On account of the high catalytic activity, affinity, and cascade strategy, the Meso-Cu-PBMCs nanozyme generated rapid multicolor displays at varying H2O2 concentrations. Under optimized conditions, the proposed sensor exhibits a preferable sensitivity of 18.14 µA µM-1, a linear range of 10 nM-25 mM, and a detection limit of 6.36 nM (S/N = 10). The reliability of the sensor was verified by detecting H2O2 in spiked human blood serum and milk samples, as well as by detecting in situ H2O2 generated from the neuron cell SH-SY5Y. Besides, the Meso-Cu-PBMCs nanozyme facilitated the catalysis of H2O2 in cancer cells, generating •OH radicals that induce the death of cancer cells (HCT-116 colon cancer cells), which holds substantial potential for application in chemodynamic therapy (CDT). This proposed strategy holds promise for simple, rapid, inexpensive, and effective intracellular biosensing and offers a novel approach to improve CDT efficacy.

Neurodegenerative effect of DAPK1 after cerebral hypoxia-ischemia is associated with its post-transcriptional and signal transduction regulations: A systematic review and meta-analysis.

Cerebral hypoxia-ischemia (CHI) causes brain aging, neurological disorders, cognitive decline, motor function impairment, and mortality. Inhibiting death-associated protein kinase 1 (DAPK1) has shown therapeutic potential against CHI, but several reports contradict its protective function, mechanism of activation, and signal transduction. Here, we systematically reviewed the role and the activation mechanism of DAPK1, and quantitatively assess the efficacy of DAPK1 inhibition (DI) methods in neuroprotection, following a CHI in animal models. Embase and PubMed were searched for relevant studies. Overall, 13 studies met the inclusion criteria, and the SYRCLE Risk of bias tool (RoB) tool was used to assess RoB. StataSE 16 was used for meta-analysis and network meta-analysis (NMA). Standardized mean differences (SMD) with 95% confidence intervals (CI) were calculated to estimate the effect size. DI was associated with the reduction of brain infarct volume (BIV) [SMD = -1.70, 95% CI (-2.10, -1.30); p = 0.00], neurological score (N.S.), neuronal degeneration, with no change in the level of in cell death [SMD = -0.83, 95% CI (-2.00, 0.35); p = 0.17], indicating the protective role of DI against CHI. No differences were found in DAPK1 mRNA and protein levels [SMD = 0.50, 95% CI (-0.05, 1.04); p = 0.07] {single-study driven; upregulated after exclusion (p = 0.01, I2 = 36.43)}, whereas phospho-DAPK1 [SMD = -2.22, 95% CI (-3.69, -0.75); p = 0.00] was downregulated and phosphorylated myosin light chain [SMD = 3.37, 95% CI (2.51, 4.96); p = 0.00] was upregulated between CHI and sham groups. Furthermore, we performed NMA to understand the molecular level at which DI offers maximum protection against BIV. Post-transcriptional inhibition (PTI; SUCRA, 82.6%) and gene knockout showed best (KO; SUCRA, 81.3%), signal transduction inhibition (STI; SUCRA, 49.5%) offered 3rd best, while catalytic activity inhibition (CAI; SUCRA, 0.3%) exhibited the lowest reduction in BIV against CHI. The results demonstrate that DI has a neuroprotective effect against CHI and DAPK1 might be regulated at the post-transcriptional and post-translational levels after CHI. Inhibiting DAPK1 at the post-transcriptional level and blocking multiple signal transduction pathways of DAPK1 could lead to better functional recovery against CHI. AVAILABILITY OF DATA AND MATERIALS: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Assessment of functional roles and therapeutic potential of integrin receptors in osteoarthritis: A systematic review and meta-analysis of preclinical studies.

BACKGROUND: Integrins are heterodimeric transmembrane receptors that mediate a variety of biological function and plays a critical role in osteoarthritis (OA) pathogenesis, which may provide new targets for the development of OA therapies. However, the roles of integrins in different stages of OA remain elusive. OBJECTIVES: This study aimed to synthesize all published preclinical evidence on the roles of integrin receptors in different stages of OA to identify the potential target for drug development in alleviating OA pathogenesis. METHODS: Major electronic databases were used to identify related original articles. The methodological quality of all included studies was appraised using the SYRCLE risk of bias tool. We used the generic inverse variance with random effects model to calculate standardized mean differences (SMDs) and 95% confidence interval (CI). RESULTS: Seventeen studies were included in this systematic review. Integrin α5ß1 activation increases the histopathological score both in early [SMD, 6.39; 95%CI (2.90, 9.87); p = 0.0003] and late [SMD, 3.41; 95%CI (2.44, 4.38); p < 0.00001] stage of OA. Integrin α5ß1 also increased the core catabolic factors like MMP-3, IL-1ß, and TNF-α. Interestingly, the inactivation of α5ß1 integrin did not change the histopathological score (p = 0.84). Similarly, ß1 integrin notably increased histopathological score at both stages of OA [early; SMD, 7.13; 95%CI (2.01, 12.24); p = 0.006]; [late; SMD, 10.25; 95%CI (5.11, 15.39); p < 0.0001], and increased the MMP-13 levels. However, integrin ß1 was upregulated at the early stage and downregulated at the late stage of OA. Furthermore, α2ß1 integrin significantly increased histopathological score [SMD, 3.14; 95%CI (2.18, 4.10); p < 0.00001] and MMP-13 [SMD, 2.24; 95%CI (0.07, 4.41); p = 0.04]. Deactivating integrin α1ß1 increased histopathological score in late [SMD, 1.53; 95%CI (0.80, 2.26); p < 0.0001], but not in early [SMD, 0.90; 95%CI (-1.65, 3.45); p = 0.49] stage of OA. CONCLUSION: This study provides evidence that α5ß1, α2ß1, and α1ß1 integrin might be the potential target for future drug development in alleviating OA pathogenesis. Further work is required to establish our findings through activating/deactivating these receptors in different stages of OA.

Pre- and post-conditioning with poly I:C exerts neuroprotective effect against cerebral ischemia injury in animal models: A systematic review and meta-analysis.

BACKGROUND: Toll-like receptor (TLR) agonist polyinosinic-polycytidylic acid (poly I:C) exerts neuroprotective effects against cerebral ischemia (CI), but concrete evidence supporting its exact mechanism of action is unclear. METHODS: We evaluated the neuroprotective role of poly I:C by assessing CI indicators such as brain infarct volume (BIV), neurological deficit score (N.S.), and signaling pathway proteins. Moreover, we performed a narrative review to illustrate the mechanism of action of TLRs and their role in CI. Our search identified 164 articles and 10 met the inclusion criterion. RESULTS: Poly I:C reduces BIV and N.S. (p = 0.00 and p = 0.03). Interestingly, both pre- and post-conditioning decrease BIV (preC p = 0.04 and postC p = 0.00) and N.S. (preC p = 0.03 and postC p = 0.00). Furthermore, poly I:C upregulates TLR3 [SMD = 0.64; CIs (0.56, 0.72); p = 0.00], downregulates nuclear factor-κB (NF-κB) [SMD = -1.78; CIs (-2.67, -0.88); p = 0.0)], and tumor necrosis factor alpha (TNF-α) [SMD = -16.83; CIs (-22.63, -11.02); p = 0.00]. CONCLUSION: We showed that poly I:C is neuroprotective and acts via the TLR3/NF-κB/TNF-α pathway. Our review indicated that suppressing TLR 2/4 may illicit neuroprotection against CI. Further research on simultaneous activation of TLR3 with poly I:C and suppression of TLR 2/4 might open new vistas for the development of therapeutics against CI.

Polypyrrole-coated nanocellulose for solar steam generation: A multi-surface photothermal ink with antibacterial and antifouling properties.

Solar energy-based steam generation holds immense potential to tackle the problem of 1.1 billion people lacking access to freshwater and 2.7 billion experiencing freshwater scarcity at least one month a year. Efficient, portable, and universal photothermal materials are required for popularity of solar-driven evaporation systems. Herein, a facile one-pot process based on solution-processed vapor phase polymerization is adopted to fabricate polypyrrole-coated cellulose nanocrystals (CNC-PPy). The CNC-PPy dispersed in water is used as an ink (CNC-PPy ink) to create photothermal layers. The developed ink is readily laminated on diverse substrates utilizing a common paintbrush that firmly attached without any delamination after drying. The optimized cellulose membrane (6 coating cycles) presents an excellent evaporation rate of 1.96 Kg m-2 h-1 with corresponding light-to-vapor efficiency of 88.92 % at 1 sun. In addition, the CNC-PPy display excellent antibacterial and antifouling properties in powder and laminated forms against E. coli and S. aureus.

Changes in Keyboard Typing Accuracy and Spatial Perception after Cardiovascular Fitness Exercise.

Background: This study aimed to identify the association between cardiopulmonary exercise and neurological activation by measuring dictation accuracy and the extent of spatial perception. Methods: First of all, the body composition of subjects was analyzed to verify their physical abnormality. The subjects were given treadmill exercise using modified Bruce protocol. Before and after the treadmill exercise, a spatial perception test and dictation task with auditory and visual stimulation were carried out to identify the changes in neurological activation. Results: The scores of spatial perception after treadmill exercise were higher than those before treadmill exercise (p < 0.05). In addition, the speed of the post-treadmill dictation task with visual stimulation was significantly increased compared to that of the pre-treadmill dictation task (p < 0.05). However, the accuracy of the post-treadmill dictation task with visual stimulation was significantly decreased compared to that of the pre-treadmill dictation task (p < 0.05). Conclusion: In this study, it was shown that spatial perception and speed of visual dictation were increased after treadmill exercise. These results suggest that cardiovascular fitness exercise increases spatial perception and typing speed by facilitating neurological activation.

Identification of exosomal biomarkers and its optimal isolation and detection method for the diagnosis of Parkinson's disease: A systematic review and meta-analysis.

Recently, there has been growing interest in exosomal biomarkers for their active targeting and specificity for delivering their cargos (proteins, lipids, nucleic acids) from the parent cell to the recipient cell. Currently, the clinical diagnosis of Parkinson's disease (PD) is mainly based on a clinician's neuropsychological examination and motor symptoms (e.g., bradykinesia, rigidity, postural instability, and resting tremor). However, this diagnosis method is not accurate due to overlapping criteria of other neurodegenerative diseases. Exosomes are differentially expressed in PD and a combination of types and contents of exosomes might be used as a biomarker in PD. Here, we systematically reviewed and meta-analyzed exosomal contents, types and sources of exosomes, method of isolation, and protein quantification tools to determine the optimum exosome-related attributes for PD diagnosis. Pubmed, Embase, and ISI Web of Science were searched for relevant studies. 25 studies were included in the meta-analysis. The Ratio of Mean (RoM) with 95% confidence intervals (CI) was calculated to estimate the effect size. Biomarker performances were rated by random-effects meta-analysis with the Restricted Maximum Likelihood (REML) method. The study protocol is available at PROSPERO (CRD42022331885). Exosomal α-synuclein (α-Syn) was significantly altered in PD patients from healthy controls [RoM = 1.67, 95% CI (0.99 to 2.35); p = 0.00] followed by tau [RoM = 1.33, 95% CI (0.79 to 1.87); p = 0.00], PS-129 [RoM = 0.97, 95% CI (0.54 to 1.40); p = 0.00], and DJ-1/PARK7 [RoM = 0.93, 95% CI (0.64 to 1.21); p = 0.00]. Central nervous system derived L1CAM exosome [RoM = 1.24, 95% CI (1.04 to 1.45); p = 0.00] from either plasma [RoM = 1.35, 95% CI (1.09 to 1.61); p = 0.00]; or serum [RoM = 1.47, 95% CI (1.05 to 1.90); p = 0.00] has been found the optimum type of exosome. The exosome isolation by ExoQuick [RoM = 1.16, 95% CI (0.89 to 1.43); p = 0.00] and protein quantification method by ELISA [RoM = 1.28, 95% CI (1.15 to 1.41); p = 0.00] has been found the optimum isolation and quantification method, respectively for PD diagnosis. This meta-analysis suggests that α-Syn in L1CAM exosome derived from blood, isolated by ExoQuick kit, and quantified by ELISA can be used for PD diagnosis.

Differential role of melatonin in healthy brain aging: a systematic review and meta-analysis of the SAMP8 model.

The relationship between oxidative stress (OS) and cellular senescence (CS) is an important research topic because of the rapidly aging global population. Melatonin (MT) is associated with aging and plays a pivotal role in redox homeostasis, but its role in maintaining physiological stability in the brain (especially in OS-induced senescence) remains elusive. Here, we systematically reviewed the differential role of MT on OS-induced senescence in the SAMP8 mouse model. Major electronic databases were searched for relevant studies. Pooled mean differences (MDs)/standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated to estimate the effect size. Overall, 10 studies met the inclusion criteria. MT treatment was associated with the reduction of lipid peroxidation (SMD = -2.00, 95% CI [-2.91, -1.10]; p < 0.0001) and carbonylated protein (MD = -5.74, 95% CI [-11.03, -0.44]; p = 0.03), and with enhancement of the reduced-glutathione/oxidized-glutathione ratio (MD = 1.12, 95% CI [0.77, 1.47]; p < 0.00001). No differences were found in catalase and superoxide dismutase activities between MT-treated and vehicle-treated groups. Furthermore, nuclear-factor-κB, cyclin-dependent kinase-5, and p53 were regulated by MT administration. MT may improve physiological stability during aging by regulating interactions in brain senescence, but acts differentially on the antioxidant system.

Recent Advances in Electrochemical and Optical Sensors for Detecting Tryptophan and Melatonin.

Tryptophan and melatonin are pleiotropic molecules, each capable of influencing several cellular, biochemical, and physiological responses. Therefore, sensitive detection of tryptophan and melatonin in pharmaceutical and human samples is crucial for human well-being. Mass spectrometry, high-performance liquid chromatography, and capillary electrophoresis are common methods for both tryptophan and melatonin analysis; however, these methods require copious amounts of time, money, and manpower. Novel electrochemical and optical detection tools have been subjects of intensive research due to their ability to offer a better signal-to-noise ratio, high specificity, ultra-sensitivity, and wide dynamic range. Recently, researchers have designed sensitive and selective electrochemical and optical platforms by using new surface modifications, microfabrication techniques, and the decoration of diverse nanomaterials with unique properties for the detection of tryptophan and melatonin. However, there is a scarcity of review articles addressing the recent developments in the electrochemical and optical detection of tryptophan and melatonin. Here, we provide a critical and objective review of high-sensitivity tryptophan and melatonin sensors that have been developed over the past six years (2015 onwards). We review the principles, performance, and limitations of these sensors. We also address critical aspects of sensitivity and selectivity, limit and range of detection, fabrication process and time, durability, and biocompatibility. Finally, we discuss challenges related to tryptophan and melatonin detection and present future outlooks.

Melatonin Maintains Anabolic-Catabolic Equilibrium and Regulates Circadian Rhythm During Osteoarthritis Development in Animal Models: A Systematic Review and Meta-analysis.

Background: The driving force behind osteoarthritis (OA) pathogenesis is an anabolic-catabolic (a/c) imbalance. Melatonin (MT) is a key player in maintaining a/c stability and mitigates OA pathogenesis, but mechanisms underlying its effects remain poorly understood. Objectives: We performed a systematic review analyzing the experimental data that support the clinical applicability of MT in the treatment of OA pathogenesis, placing particular emphasis on the regulation of circadian rhythms and a/c balance. Methods: Major electronic databases and grey literature were used to identify related original articles. Methodological quality of all selected studies was evaluated using the SYRCLE risk of bias tool. Pooled mean differences (MDs)/standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated to estimate the effect size. Results: Eleven trials were included in this systematic review. Compared with the control group, MT significantly decreased the levels of interleukin-1ß (IL-1ß; SMD = -5.45; 95% CI [-6.78, -4.12]; p < 0.00001, and histological grading scale (SMD = -3.46; 95% CI, [-5.24, -1.68]; p < 0.0001). MT significantly increased the transforming growth factor-ß1 (TGF-ß1; SMD = 1.17; 95% CI [0.31, 2.03]; p < 0.0007). Furthermore, core circadian clock genes Per2 and Cry1 mRNA levels were regulated by MT treatment in OA progression. Conclusion: MT may maintain a/c balance and regulate circadian rhythms during OA development. MT could be used in as adjunct with other interventions to manage pain and OA severity.

Mesenchymal Stem Cell-Derived Exosomes Exhibit Promising Potential for Treating SARS-CoV-2-Infected Patients.

The novel coronavirus severe acute respiratory syndrome-CoV-2 (SARS-CoV-2) is responsible for COVID-19 infection. The COVID-19 pandemic represents one of the worst global threats in the 21st century since World War II. This pandemic has led to a worldwide economic recession and crisis due to lockdown. Biomedical researchers, pharmaceutical companies, and premier institutes throughout the world are claiming that new clinical trials are in progress. During the severe phase of this disease, mechanical ventilators are used to assist in the management of outcomes; however, their use can lead to the development of pneumonia. In this context, mesenchymal stem cell (MSC)-derived exosomes can serve as an immunomodulation treatment for COVID-19 patients. Exosomes possess anti-inflammatory, pro-angiogenic, and immunomodulatory properties that can be explored in an effort to improve the outcomes of SARS-CoV-2-infected patients. Currently, only one ongoing clinical trial (NCT04276987) is specifically exploring the use of MSC-derived exosomes as a therapy to treat SARS-CoV-2-associated pneumonia. The purpose of this review is to provide insights of using exosomes derived from mesenchymal stem cells in management of the co-morbidities associated with SARS-CoV-2-infected persons in direction of improving their health outcome. There is limited knowledge of using exosomes in SARS-CoV-2; the clinicians and researchers should exploit exosomes as therapeutic regime.

Detection of C-Reactive Protein Using Histag-HRP Functionalized Nanoconjugate with Signal Amplified Immunoassay.

Ultrasensitive detection of biomarkers is highly significant for disease prognosis and public health treatment. Despite wide acceptance in routine laboratory tests, the conventional enzyme-linked immunosorbent assay (ELISA) has been of limited use for early biomarker detection due to insufficient sensitivity and multiple long incubation time. Several nanoprobes have been introduced to circumvent the limitation, however, rapid, simple, and chemical-free nanoprobe synthesis and sensitive detection methods, particularly for ELISA, are still lacking. In this study, we have synthesized a gold nanoprobe, conjugated with multiple 6X-histidine (6X-his) peptide and nickel-horseradish peroxidase (Ni2+-HRP), for enhancing the colorimetric signal in ELISA. The developed nanoprobe has been tested for the detection of immunologically significant C-reactive protein (CRP) in ELISA format. The performance of designed probe is validated by testing standard and serum samples, and the detection limit of 32.0 pg/mL with R2 = 0.98 is confirmed. Furthermore, a comparative analysis of the developed nanoprobe was performed with ELISA developed on conventional guidelines, the proposed immunoassay showed an increase of 12-fold sensitivity for detecting CRP due to the high loading of 6Xhis peptide and binding of multiple Ni2+-HRP on a gold nanoparticle. Additionally, the proposed assay provides a simple, fast, and cost-efficient (not requiring multiple antibodies) detection of CRP with easy nanoprobe synthesis. Moreover, the developed Histag-HRP functionalized nanoconjugate immunoassay is flexible and can be applied to other biomarkers efficiently by using disease specific antibody.

Protective Effects of Melatonin against Severe Burn-Induced Distant Organ Injury: A Systematic Review and Meta-Analysis of Experimental Studies.

Extensive burns result in a local wound response and distant-organ injury (DOI) caused by oxidative-stress and inflammation. Melatonin (MT) shows promise in alleviating oxidative-stress and inflammation, but its role in thermal injury is largely unexplored. The present systematic review and meta-analysis were designed to assess the effects of MT on oxidative-stress and inflammatory markers against severe burn-induced DOI. Mean difference (MD)/standard mean difference (SMD) with 95% confidence interval (CI) were estimated using fixed-effect/random-effects models. Eighteen experimental studies met the inclusion criteria. Compared with the control group, MT significantly decreased the levels of malondialdehyde (SMD, -1.03; 95% CI, -1.30, -0.76, p < 0.00001) and 4-hydroxynonenal (MD, -1.06; 95% CI, -1.57, -0.56, p < 0.0001). Additionally, MT increased the levels of glutathione (SMD, 1.94; 95% CI, 1.27, 2.61, p < 0.00001) and superoxide-dismutase (SMD, 0.76; 95% CI, 0.08, 1.45, p = 0.03). Finally, MT significantly decreased the levels of tumor necrosis factor-α (SMD, -1.34; 95% CI, -1.92 to -0.77; p < 0.00001) and C-reactive protein (MD, -12.67; 95% CI, -16.72 to -8.62; p < 0.00001). Meta-analysis indicates that severe burn followed by immediate MT (10 mg/kg) intervention shows significant beneficial effects after 24-h against DOI by regulating oxidative-stress and the inflammatory response.