Advances in Colon-Targeted Drug Delivery Systems: Innovative Strategies for Treating Colonic Disorders and Prospects for the Future.

Colon-specific targeting delivery systems have drawn a great deal of attention because they represent potential vehicles for treating colonic disorders like diverticulitis, colitis, salmonellosis, Crohn's disease, etc. with less systemic adverse effects as well as for the better oral delivery of many therapeutics that are prone to enzymatic and acidic deterioration in the upper GI tract. Smart polymeric delivery systems in particular have been investigated as "intelligent" delivery systems capable of releasing entrapped pharmaceuticals at the proper time & site of action in response to certain physiological stimuli. The creation of novel polymers & crosslinkers with improved biodegradability and biocompatibility would expand and enhance applications now in use. The development of polymeric systems could result in more precise and programmable drug delivery/therapies. In addition, newer advancements have led to the development of numerous ground-breaking techniques for directing a medication molecule to the colon. This review highlighted formulation techniques pH-dependent, time-dependent, enzyme sensitive, magnetically dependent, ligand-receptor mediated, and microflora-activated systems. Moreover, several methods have been put forth that make use of the innovative idea of such delivery systems, and mechanisms in which the release of drugs is regulated by pH and time as well as pH and the colon's bacteria.

Multimodal action of phosphodiesterase 5 inhibitors against neurodegenerative disorders: An update review.

Phosphodiesterase type 5 (PDE5) is an enzyme primarily found in the smooth muscle of the corpus cavernosum and also highly expressed in the substantia nigra, cerebellum, caudate, hippocampal regions and cerebellar purkinje cells, responsible for selectively breaking down cyclic guanosine monophosphate (cGMP) into 5'-GMP and regulate intracellular cGMP levels. As a second messenger, cyclic GMP enhances signals at postsynaptic receptors and triggers downstream effector molecules, leading to changes in gene expression and neuronal responses. Additionally, cGMP signaling transduction cascade, present in the brain, is also essential for learning and memory processes. Mechanistically, PDE5 inhibitors share structural similarities with cGMP, competitively binding to PDE5 and inhibiting cGMP hydrolysis. This action enhances the effects of nitric oxide, resulting in anti-inflammatory and neuroprotective effects. Neurodegenerative disorders entail the progressive loss of neuron structure, culminating in neuronal cell death, with currently available drugs providing only limited symptomatic relief, rendering neurodegeneration considered incurable. PDE5 inhibitors have recently emerged as a potential therapeutic approach for neurodegeneration, neuroinflammation, and diseases involving cognitive impairment. This review elucidates the principal roles of 3',5'-cyclic adenosine monophosphate (cAMP) and cGMP signaling pathways in neuronal functions, believed to play pivotal roles in the pathogenesis of various neurodegenerative disorders. It provides an updated assessment of PDE5 inhibitors as disease-modifying agents for conditions such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, cerebral ischemia, Huntington's disease, and neuroinflammation. The paper aims to review the current understanding of PDE5 inhibitors, which concurrently regulate both cAMP and cGMP signaling pathways, positing that they may exert complementary and synergistic effects in modifying neurodegeneration, thus presenting a novel direction in therapeutic discovery. Moreover, the review provides critical about biological functions, therapeutic potentials, limitations, challenges, and emerging applications of selective PDE5 inhibitors. This comprehensive overview aims to guide future academic and industrial endeavors in this field.

Dietary Natural Flavonoids: Intervention for MAO-B Against Parkinson's Disease.

Parkinson's disease (PD) stands as the second most common neurological disorder after Alzheimer's disease, primarily affecting the elderly population and significantly compromising their quality of life. The precise etiology of PD remains elusive, but recent research has shed light on potential factors, including the formation of α-synuclein aggregates, oxidative stress, neurotransmitter imbalances, and dopaminergic neurodegeneration in the substantia nigra pars compacta (SNpc) region of the brain, culminating in motor symptoms such as bradykinesia, akinesia, tremors, and rigidity. Monoamine oxidase (MAO) is an essential enzyme, comprising two isoforms, MAO-A and MAO-B, responsible for the oxidation of monoamines such as dopamine. Increased MAO-B activity is responsible for decreased dopamine levels in the SNpc region of mid brain which is remarkably associated with the pathogenesis of PD-like manifestations. Inhibitors of MAO-B enhance striatal neuronal responses to dopamine, making them valuable in treating PD, which involves dopamine deficiency. Clinically approved MAO-B inhibitors such as selegiline, L-deprenyl, pargyline, and rasagiline are employed in the management of neurodegenerative conditions associated with PD. Current therapeutic interventions including MAO-B inhibitors for PD predominantly aim to alleviate these motor symptoms but often come with a host of side effects that can be particularly challenging for the patients. While effective, they have limitations, prompting a search for alternative treatments, there is a growing interest in exploring natural products notably flavonoids as potential sources of novel MAO-B inhibitors. In line with that, the present review focuses on natural flavonoids of plant origin that hold promise as potential candidates for the development of novel MAO-B inhibitors. The discussion encompasses both in vitro and in vivo studies, shedding light on their potential therapeutic applications. Furthermore, this review underscores the significance of exploring natural products as valuable reservoirs of MAO-B inhibitors, offering new avenues for drug development and addressing the pressing need for improved treatments in PD-like pathological conditions. The authors of this review majorly explore the neuroprotective potential of natural flavonoids exhibiting notable MAO-B inhibitory activity and additionally multi-targeted approaches in the treatment of PD with clinical evidence and challenges faced in current therapeutic approaches.

Effect of Electrode Montage on Frequency Tuning Properties of Air-Conducted Ocular Vestibular-Evoked Myogenic Potential.

OBJECTIVES: The use of a 500 Hz tone burst over other frequencies was adopted for the clinical recording of ocular vestibular-evoked myogenic potential (oVEMP) on the basis that this stimulus frequency produces larger response amplitudes (frequency tuning) than the other frequencies. However, the possibility of reflex contamination due to a spatially displaced reference electrode from the muscle of the response origin raises questions about using an infraorbital (IO) montage. Nonetheless, the belly-tendon (BT) montage, which places both the recording electrodes over the inferior oblique muscle, increases the chances of obtaining a response with greater contribution from the inferior oblique muscle. However, whether this response continues to show the frequency tuning to 500 Hz is not known. Therefore, the present study aimed to examine the frequency tuning of oVEMP using various electrode montages. DESIGN: Thirty-eight young adults underwent simultaneous oVEMP recording from IO, BT, chin-referenced, and sternum-referenced electrode montages in response to 250, 500, 750, 1000, 1500, 2000, 3000, and 4000 Hz tone bursts. RESULTS: The frequency tuning most often coincided with a 750-Hz tone burst irrespective of the montage, with the BT montage exhibiting significantly higher response rates and larger peak to peak amplitudes than other montages (p < 0.008). Further, there was a "substantial" agreement on frequency tuning between BT and IO montages. CONCLUSIONS: With better response rates and response amplitudes yet similar frequency tuning to the IO montage, the BT montage can be a better option for the clinical recording of oVEMP across frequencies.

Development and Standardization of Modified Simultaneous Multifrequency (SiMFy) Stimulus for Recording oVEMP And Its Interaction with the Alternate Electrode Montages.

BACKGROUND: Simultaneous Multifrequency (SiMFy) is a time-saving and reliable stimulus to determine the frequency tuning of ocular vestibular-evoked myogenic potential (oVEMP); however, the absence of 4000 Hz in SiMFy potentially makes it a less potent tool for the diagnosis of Superior semicircular canal dehiscence, a pathology with an ever-increasing prevalence. Further, SiMFy was validated using only the infra-orbital (IO) electrode montage. However, the recordings obtained using the IO montage might be susceptible to reference contamination introduced by a small separation between the recording electrodes, and also susceptible to reflex impurity due to the spatially displaced reference electrode from the inferior oblique muscle (IOM), rendering it vulnerable to picking up responses from other muscles. Nonetheless, little is known about the similarities/differences between the SiMFy-induced oVEMPs using alternate montages [belly-tendon (BT), chin-reference (CR), and sternum-reference (SR)] and the non-simultaneous multifrequency oVEMPs (NSM-oVEMPs) using the IO montage. PURPOSE OF THE STUDY: To develop a modified SiMFy stimulus and investigate its effects on frequency tuning of oVEMP using various electrode montages. RESEARCH DESIGN: Within-subject experimental design. STUDY SAMPLE: Thirty-three healthy adults aged 20-30 years. DATA COLLECTION AND ANALYSIS: Tone bursts of octave and mid-octave frequencies from 250 Hz to 4000 Hz were generated and concatenated to create the modified SiMFy stimulus. All participants underwent non-simultaneous multifrequency oVEMPs and modified SiMFy oVEMPs using BT, CR, SR, and IO montages simultaneously. The response rate, peak-to-peak amplitude, and frequency tuning were compared between NSM-oVEMP and modified SiMFy oVEMP and also between the electrode montages. RESULTS: BT montage recorded the largest amplitude among the montages in non-simultaneous multifrequency stimulation and modified SiMFy stimulation. Although the response rates were comparable, the modified SiMFy produced significantly lower oVEMP amplitudes than the non-simultaneous multifrequency stimulation within each electrode montage (p < 0.05). A moderate-to-strong agreement on frequency tuning existed between the non-simultaneous multifrequency stimuli and modified SiMFy stimulus for all the montages, except for the SR montage. CONCLUSIONS: Although the modified SiMFy produces smaller amplitude oVEMPs than the non-simultaneous multifrequency stimulation for the respective montages, its use in combination with the BT montage yields higher response rates and larger peak-to-peak amplitudes than the non-simultaneous multifrequency recording using IO montage.

Understanding Mechanisms and Key Factors Influencing Melanogenesis for the Management of Melasma: An Updated Review.

Melanocytes are highly specialized dendritic cells that deliver melanin to keratinocytes in melanosomes, which are subcellular organelles where melanin is produced and stored. Mammal's skin, hair, and eyes all contain the complex pigment melanin, which gives them color and ultraviolet protection. Melanins have the potential to be free radical sinks and are strong cation chelators. Amino acid tyrosine and its metabolite, dopa, are the precursors to complex metabolic processes that end with melanin production. Melanocytes generate different types and amounts of melanin, which is defined genetically and is impacted by several extrinsic and intrinsic factors such as hormone fluctuations, inflammation, age, and ultraviolet radiation exposure, leading to the stimulation of numerous melanogenesis pathways. Melasma, a common skin pigmentation condition, is associated with the overproduction of melanin and is characterized by brown to gray-brown and black spots that mostly affect the face. The present review addresses the regulatory mechanisms and signaling pathways involved in skin pigmentation with an emphasis on the altered melanogenesis that causes melasma and hyperpigmentation. The current study also illustrates the available treatment options with cellular and molecular mechanisms for the management of melasma. Understanding the mechanism of the pigmentation process may help researchers develop new therapeutic strategies and novel drugs for the management of melasma.

Heterologous expression, purification and single step efficient refolding of recombinant tissue plasminogen activator (Reteplase) from E. coli.

Reteplase (recombinant plasminogen activator, rPA) is a mutant non-glycosylated tissue-type plasminogen activator (tPA) containing 355 amino acids with longer half-life and promising thrombolytic activity than its original counterpart, full length tPA. In this study, we aimed to produce and optimize the purification process of recombinant tissue-type plasminogen activator (tPA) known as Reteplase (rPA). Reteplase cDNA synthesized from total mRNA isolated from human placenta was PCR amplified, cloned into a pET-28a(+) E. coli expression vector and expressed in Rosetta-gami 2 E. coli (NovagenⓇ) host. rPA was expressed as an inclusion body in E. coli and its biological activity was achieved after single step solubilization, purification and refolding. We exploited the strategy of Slow Refolding using Gradual Dialysis (SRGD) in which a refolding buffer containing glutathione oxidized (1 mM GSSG) and glutathione reduced (3 mM GSH) and pH 9.0 was used. Using the SRGD method, we were able to successfully obtain the protein in its active form. We obtained 4.26 mg of active refolded protein from a 50 mL culture that was scaled up in a bioreactor. The purity and homogeneity of rPA was evaluated by SDS-PAGE, Western blotting and mass spectrometry. Circular dichroism spectroscopy was conducted to evaluate the refolding and stability of the refolded rPA in comparison to reference standard rPA. The thrombolytic potential of rPA was assessed by fibrin plate assay and In Vitro clot lysis assay. The presented protocol offers a viable approach for enhancing both the yield and refolding efficiency of reteplase, potentially resulting in an increase in yield.

Therapeutic Expedition of Luteolin against Brain-related Disorders: An Updated Review.

Brain-related disorders include neuroinflammation, neurodegenerative disorders, and demyelination, which ultimately affect the quality of life of patients. Currently, brain-related disorders represent the most challenging health problem worldwide due to complex pathogenesis and limited availability of drugs for their management. Further, the available pharmacotherapy accompanies serious side effects, therefore, much attention has been directed toward the development of alternative therapy derived from natural sources to treat such disorders. Recently, flavonoids, natural phytochemicals, have been reported as a treatment option for preventing brain aging and disorders related to this. Among these flavonoids, dietary luteolin, a flavone, is found in many plant products such as broccoli, chamomile tea, and honeysuckle bloom having several pharmacological properties including neuroprotective activities. Therefore, the objective of this paper is to compile the available literature regarding the neuroprotective potential of luteolin and its mechanism of action. Luteolin exerts notable anti-inflammatory, antioxidant, and antiapoptotic activity suggesting its therapeutic efficacy in different neurological disorders. Numerous in-vivo and in-vitro experiments have revealed that luteolin exhibits neuroprotective potential via up-regulating the ER/ERK, PI3AKT, Nrf2 pathways and down-regulating the MAPK/JAK2STAT and NFκB pathways. Taking into account of available facts regarding the neuroprotective efficacy of luteolin, the current study highlights the beneficial effects of luteolin for the prevention, management, and treatment of different neurological disorders. Thus, luteolin can be considered an alternative for the development of new pharmacophores against various brain-related disorders.

Nuclear Factor Kappa B: A Nobel Therapeutic Target of FlavonoidsAgainst Parkinson's Disease.

Parkinson's disease (PD), the most common brain-related neurodegenerative disorder, is comprised of several pathophysiological mechanisms, such as mitochondrial dysfunction, neuroinflammation, aggregation of misfolded alpha-synuclein, and synaptic loss in the substantia nigra pars compacta region of the midbrain. Misfolded alpha-synuclein, originating from damaged neurons, triggers a series of signaling pathways in both glial and neuronal cells. Activation of such events results in the production and expression of several proinflammatory cytokines via the activation of the nuclear factor κB (NF-κB) signaling pathway. Consequently, this cascade of events worsens the neurodegenerative processes, particularly in conditions, such as PD and synucleinopathies. Microglia, astrocytes, and neurons are just a few of the many cells and tissues that express the NF-κB family of inducible types of transcription factors. The dual role of NF-κB activation can be crucial for neuronal survival, although the classical NF-κB pathway is important for controlling the generation of inflammatory mediators during neuroinflammation. Modulating NF-κB-associated pathways through the selective action of several agents holds promise for mitigating dopaminergic neuronal degeneration and PD. Several naturally occurring compounds in medicinal plants can be an effective treatment option in attenuating PD-associated dopaminergic neuronal loss via selectively modifying the NF-κB-mediated signaling pathways. Recently, flavonoids have gained notable attention from researchers because of their remarkable anti-neuroinflammatory activity and significant antioxidant properties in numerous neurodegenerative disorders, including PD. Several subclasses of flavonoids, including flavones, flavonols, isoflavones, and anthocyanins, have been evaluated for neuroprotective effects against in vitro and in vivo models of PD. In this aspect, the present review highlights the pathological role of NF-κB in the progression of PD and investigates the therapeutic potential of natural flavonoids targeting the NF-κB signaling pathway for the prevention and management of PD-like manifestations with a comprehensive list for further reference. Available facts strongly support that bioactive flavonoids could be considered in food and/or as lead pharmacophores for the treatment of neuroinflammation-mediated PD. Furthermore, natural flavonoids having potent pharmacological properties could be helpful in enhancing the economy of countries that cultivate medicinal plants yielding bioactive flavonoids on a large scale.

Chemically Transformed Ag2 Te Nanowires on Polyvinylidene Fluoride Membrane For Flexible Thermoelectric Applications.

Flexible thermoelectric devices of nanomaterials have shown a great potential for applications in wearable to remotely located electronics with desired shapes and geometries. Continuous powering up the low power flexible electronics is a major challenge. We are reporting a flexible thermoelectric module prepared from silver telluride (Ag2 Te) nanowires (NWs), which are chemically transformed from uniquely synthesized and scalable tellurium (Te) NWs. Conducting Ag2 Te NWs composites have shown an ultralow total thermal conductivity ~0.22 W/mK surpassing the bulk melt-grown Ag2 Te ~1.23 W/mK at ~300 K, which is attributed to the nanostructuring of the material. Flexible thermoelectric device consisting of 4 legs (n-type) of Ag2 Te NWs on polyvinylidene fluoride membrane displays a significant output voltage (Voc ) ~2.3 mV upon human touch and Voc ~18 mV at temperature gradient, ΔT ~50 K, which shows the importance of NWs based flexible thermoelectric devices to power up the low power wearable electronics.

Electrode Montage Induced Changes in Air-Conducted Ocular Vestibular-Evoked Myogenic Potential.

OBJECTIVES: Stimulus and recording parameters are pivotal for shaping the ocular vestibular-evoked myogenic potential (oVEMP). In the last decade, several attempts were made to identify the optimum electrode placement site to improve the oVEMP responses. A vast majority of these found larger response amplitudes for alternate electrode montages like belly-tendon (BT), chin-referenced (CR), and/or sternum-referenced montages than the clinically used infra-orbital montage. However, no study has yet compared all alternate electrode montages in a simultaneous recording paradigm to eliminate other confounding factors. Also, no study has compared all of them for their test-retest reliability, waveform morphology, and signal-to-noise ratio. Therefore, the decision on which among these electrode montages is best suited for oVEMP acquisition remains opaque. The present study aimed to investigate the effects of various electrode montages on oVEMP's response parameters and to determine the test-retest reliability of each of these in clinically healthy individuals using a simultaneous recording paradigm. DESIGN: This study had a within-subject experimental design. Fifty-five young healthy adults (age range: 20-30 years) underwent contralateral oVEMP recording using infra-orbital, BT, chin-referenced, and sternum-referenced electrode montages simultaneously using a four-channel evoked potential system. RESULTS: BT montage had a significantly shorter latency, larger amplitude, higher signal-to-noise ratio, and better morphology than other alternate montages ( p < 0.008). Further, all electrode montages of the current study showed fair/moderate to excellent test-retest reliability. CONCLUSIONS: By virtue of producing significantly better response parameters than the other electrode montages, BT montage seems better suited to the recording of oVEMP than the known electrode montages thus far.

Treatment efficacy of repositioning maneuvers in multiple canal benign paroxysmal positional vertigo: a systematic review and meta-analysis.

Introduction: Benign paroxysmal positional vertigo (BPPV) involving the posterior canal is more common than other canals; however, simultaneous involvement of multiple canals can be seen up to 20% of all BPPV cases. The diagnosis and management of multiple canal BPPV can be quite challenging due to the complexity of findings. Therefore, this systematic review and meta-analysis aimed at unveiling the most effective repositioning strategy for the treatment of multiple canal BPPV. Methods: A literature search through PubMed, Scopus, and Web of Science databases was conducted using search terms such as BPPV, multiple canals, bilateral BPPV, repositioning maneuvers etc. After duplicate removal, the retained articles underwent various stages of elimination by two independent reviewers, and a third reviewer resolved the discrepancy between them. Results: A total of 22 articles were included in the systematic review. These publications documented 5,196 patients diagnosed with BPPV, of which 513 had multiple canal BPPV. Of 295 individuals with multiple canal BPPV, 58.9% were effectively treated in 1 session, whereas 18.3 and 4.4% achieved a symptom-free state after two and three sessions, respectively. Failure of treatment using repositioning maneuvers was found in 18.4%. Possible implications: This study offers insight into the real world of BPPV management in single and multiple canal BPPV. It is evident that repositioning maneuvers provide rapid and long-lasting relief of BPPV in most single canal BPPV patients; however, multiple canal BPPV often requires repeated treatment, and the risk of recurrence is higher in this variety than the single canal BPPV.

Role of Astrogliosis in the Pathogenesis of Parkinson's Disease: Insights into Astrocytic Nrf2 Pathway as a Potential Therapeutic Target.

Recently, Parkinson's disease (PD) has become a remarkable burden on families and society with an acceleration of population aging having several pathological hallmarks such as dopaminergic neuronal loss of the substantia nigra pars compacta, α-synucleinopathy, neuroinflammation, autophagy, last but not the least astrogliosis. Astrocyte, star-shaped glial cells perform notable physiological functions in the brain through several molecular and cellular mechanisms including nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. It has been well established that the downregulation of the astrocytic Nrf2 signaling pathway plays a crucial role in the pathogenesis of PD because it is a master regulator of cellular defense mechanism along with a regulator of numerous detoxifying and antioxidant enzymes gene expression. Fascinatingly, upregulation of the astrocytic Nrf2 signaling pathway attenuates the degeneration of nigrostriatal neurons, restores neuronal proliferation, rejuvenates astrocytic functions, and exhibits neuroprotective effects via numerous cellular and molecular mechanisms in the PD-like brain of the experimental animal. Here, we discuss the numerous in-vitro and in-vivo studies that evaluate the neuroprotective potential of the astrocytic Nrf2 signaling pathway against experimentally-induced PD-like manifestation. In conclusion, based on available preclinical reports, it can be assumed that the astrocytic Nrf2 signaling pathway could be an alternative target in the drug discovery process for the prevention, management, and treatment of PD.

Usefulness of masseter vestibular evoked myogenic potentials in identifying brainstem dysfunction among individuals with multiple sclerosis.

OBJECTIVE: The present study aimed to investigate the findings of cervical, ocular and masseter vestibular evoked myogenic potentials (cVEMP, oVEMP and mVEMP) among Multiple sclerosis (MS) and correlate with clinical and MRI findings. DESIGN: Standard group comparison research design. STUDY SAMPLE: Individuals with relapsing-remitting MS (n = 45) and age-sex-matched controls (n = 45) were the participants. All of them underwent case history, neurological examination, cVEMP, oVEMP and mVEMP testing. MRI was obtained only for MS participants. RESULTS: Abnormal result on at least one vestibular evoked myogenic potential (VEMP) sub-type was evidenced in 95.56% of participants whereas, unilateral or bilateral abnormal result on all three VEMP sub-types was observed in 60% of participants. The mVEMP abnormality was higher (82.22%) than cVEMP (75.56%) and oVEMP (75.56%) abnormalities but the differences were not significant (p > 0.05). There was no significant association of VEMP abnormalities with the presence of the brainstem symptoms, the brainstem signs, or the MRI lesions (p > 0.05). In the MS group, 38% had normal brainstem MRI; however, mVEMP, cVEMP and oVEMP abnormalities were evidenced in 82.4%, 64.7% and 52.94%, respectively. CONCLUSIONS: Among the three VEMP sub-types, mVEMP appears to be of greater value in identifying silent brainstem dysfunction undetected by clinical and MRI findings in the MS population.

Crystal structure of Synechococcus phycocyanin: implications of light-harvesting and antioxidant properties.

Phycobiliproteins is a family of chromophore-containing proteins having light-harvesting and antioxidant capacity. The phycocyanin (PC) is a brilliant blue coloured phycobiliprotein, found in rod structure of phycobilisome and has been widely studied for their therapeutic and fluorescent properties. In the present study, the hexameric assembly structure of phycocyanin (Syn-PC) from Synechococcus Sp. R42DM is characterized by X-ray crystallography to understand its light-harvesting and antioxidant properties. The crystal structure of Syn-PC is solved with 2.15 Å resolution and crystallographic R-factors, Rwork/Rfree, 0.16/0.21. The hexamer of Syn-PC is formed by heterodimer of two polypeptide chains, namely, α- and ß-subunits. The structure is analysed at atomic level to reveal the chromophore microenvironment and possible light energy transfer mechanism in Syn-PC. The chromophore arrangement in hexamer, deviation angle and distance between the chromophore contribute to the energy transfer efficiency of protein. The structural attributes responsible for the antioxidant potential of Syn-PC are recognized and annotated on its 3-dimensional structure. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03665-1.

Heterologous expression and biochemical characterization of novel multifunctional thermostable α-amylase from hot-spring metagenome.

Hot-springs are regarded as the best source of industrially significant biocules and one of the unique locations for extremophiles. The α-amylase is one of the most important enzymes used in starch consuming industries, where the need of thermostability is paramount. In this study, the full metagenome sequences obtained from the soil of Tuwa hot-spring (Gujarat, India) were examined for the presence of several thermostable enzymes using bioinformatic techniques. The whole gene sequence for α-amylase was found from the metagenome. The α-amylase gene was amplified, cloned, and expressed in Escherichia coli and further characterized in vitro. The rm-α-amylase was found optimally active at 60 °C and at pH 6.0 and showed significantly high activity in 0.1 mM Co2+ as well as in other heavy metal ions without any effect on its thermostability. Apart from α-amylase activity the purified rm-α-amylase was also shown to hydrolyse agar, xylan, pectin, alginate and cellulose. To our knowledge, this is the first report of a new, multifunctional, thermostable amylase that was discovered from the hot-spring metagenomes. Owing to their multifunctionality, resilience towards high temperature and heavy metal ions, stability with solvents, additives and inhibitors, rm-α-amylase can be exploited for a variety of biotechnological applications.

A Research Update on Exendin-4 as a Novel Molecule Against Parkinson's Disease.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder, and its consequences severely influence the quality of a patient's life and mobility. PD is characterized by bradykinesias with tremors and/or rigidity. Pathophysiologically, PD is associated with the gradual degeneration of dopaminergic neurons in the substantia nigra pars compacta of the midbrain, neuroinflammation, increased accumulation of the alpha (α)-synuclein, overburden of oxidative stress, and mitochondrial dysfunction. To date, there are no effective therapies with underlying shreds of evidence that alters the progression of PD. Exendin-4, a glucagon-like peptide 1 (GLP-1) receptor agonist, has gained attention for its tremendous neuroprotective potential against numerous neurodegenerative disorders, including PD. Further, several pieces of research evidence have suggested the beneficial role of Exendin-4 in PD-like experimental models. The present review article highlights the preclinical and clinical evidence of the therapeutic benefits of Exendin-4 against PD. Exendin-4 reverses the PD-like symptoms in experimental animals by dramatically minimizing the loss of dopaminergic neuronal and accumulation of α-synuclein in the PD-like brain. Further, it also reduces the mitochondrial toxicity and expression of pro-inflammatory mediators such as tumor necrosis factor (TNF)-α and interleukin (IL)-1ß. These observations designate that Exendin-4 is a multifactorial compound that could be considered a safe, effective, and new ingredient for developing clinically useful pharmacotherapy for managing PD-like manifestations.

Utility of Inter-Frequency Amplitude Ratio of Vestibular-Evoked Myogenic Potentials in Identifying Meniere's Disease: A Systematic Review and Meta-Analysis.

OBJECTIVES: A recently devised parameter of vestibular-evoked myogenic potential (VEMP) based on the principles of frequency tuning is the inter-frequency amplitude ratio (IFAR). It refers to the ratio of the amplitude of 1000 Hz tone burst evoked VEMP to 500 Hz evoked tone burst. A pathology like Meniere's disease changes the frequency response and alters the frequency tuning of the otolith organs. Because IFAR is based on the principle of frequency tuning of VEMP, it is likely to help identify Meniere's disease. Few studies in the last decade have investigated the utility of IFAR in identifying Meniere's disease. However, a systematic review and a meta-analysis on IFAR in Meniere's disease are lacking. The present study investigates whether the IFAR of VEMP helps identify Meniere's disease and differentiates it from healthy ears and other vestibular pathologies. DESIGN: The present study is a systematic review and a meta-analysis. The studies investigating the IFAR of cervical and ocular VEMPs in Meniere's disease, healthy controls, and other vestibular pathologies were searched across research databases such as PubMed, Science Direct, and Scopus. The search strategy was developed using the PICO (population, intervention, comparison, and outcomes) format, and Medical Subject Headings (MeSH) terms and Boolean operators were employed. The systematic review was performed using the Rayyan software, whereas the Review Manager software was used to carry out the meta-analysis. A total of 16,605 articles were retrieved from the databases. After the duplicate removal, 2472 articles remained. These were eliminated using title screening, abstract screening, and full-length inspections. A total of nine articles were found eligible for quality assessment and meta-analysis, and the New Castle-Ottawa Scale was used for quality assessment. After the data extraction, 24 six articles were found to have the desired data format for the meta-analysis. RESULTS: The results showed significantly higher IFAR in the affected ears of individuals in the Meniere's disease group than in the control group's unaffected ears. There was no significant difference between the unaffected ears of individuals in the Meniere's disease group and the ears of the control group. The only study on Meniere's disease and benign paroxysmal positional vertigo found significantly larger ocular VEMP IFAR in ears with Meniere's disease than in benign paroxysmal positional vertigo. CONCLUSIONS: This systematic review and meta-analysis found IFAR efficient in differentiating Meniere's disease from healthy controls. We also found an enhanced IFAR as a potential marker for Meniere's disease. However, more investigations are needed to confirm the utility of an enhanced IFAR value in the exclusive identification of Meniere's disease.

Crystal structure analysis of phycoerythrin from marine cyanobacterium Halomicronema.

Phycoerythrin (PE) is green light-absorbing pigment-protein that assists in efficient light harvesting in cyanobacteria and red-algae. PE in cyanobacteria stays less studied so far as compared to that in red algae. In this study, PE from marine cyanobacteria Halomicronema sp. R31DM is purified and subjected for its structural characterisation by X-ray crystallography in order to understand its light-harvesting characteristics. The crystal structure is solved to a resolution-limit of 2.21 Å with reasonable R-factors values, 0.16/0.21 (Rwork/ Rfree). PE forms hexamer of hetero-dimers made up of two peptide chains, α- and ß-subunits containing 2 and 3 phycoerythrobilin (PEB) chromophores covalently attached to them, respectively. Geometry of five chromophores is analysed along with their relative position within the PE hexamer. Also, their interactions with the surrounding microenvironment are analysed. The plausible energy transfer pathways in hexamer structure have been predicted based on relative position and geometry of chromophores. This structure enriches the structural information of cyanobacterial PE in order to understand its light-harvesting capacity.Communicated by Ramaswamy H. Sarma.