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Anti-reflux medication use in preterm infants

Binti Abdul Hamid H, Szatkowski L, Budge H, Ojha S

Pediatr Res, 2021 Oct 29.
PMID: 34716422 DOI: 10.1038/s41390-021-01821-y

BACKGROUND: Current recommendations do not support the use of anti-reflux medications to treat gastro-oesophageal reflux disease (GORD) among preterm infants.
OBJECTIVE: To describe the prevalence of GORD and the use of anti-reflux medications amongst very preterm infants (<32 weeks' gestational age (GA)) in neonatal units in England and Wales.
DESIGN: Retrospective cohort study using the National Neonatal Research Database.
RESULTS: Among 58,108 infants [median GA (IQR) 29 (27-30) weeks], 15.8% (n = 9191) had a diagnosis of GORD and 36.9% (n = 12,446) received anti-reflux medications. Those who received anti-reflux medications were more preterm [GA, median (IQR): medications, 28 (26-30) vs. no medications, 30 (28-31); p
Fulltext Nutritional practices and growth of preterm infants in two neonatal units in the UK and Malaysia: a prospective exploratory study

Abdul Hamid H, Szatkowski L, Budge H, Cheah FC, Ojha S

BMJ Paediatr Open, 2021;5(1):e001153.
PMID: 34514178 DOI: 10.1136/bmjpo-2021-001153

Objective: To explore differences in nutritional practices and growth outcomes among preterm infants in neonatal units in Malaysia and the UK.
Design: Prospective exploratory study of infants born at <34 weeks gestational age (GA).
Setting: Two neonatal units, one in Malaysia and one in the UK (May 2019 to March 2020).
Methods: Data collected from birth until discharge and compared between units.
Results: From 100 infants included, median GA (IQR) was 31 (30-33) and mean±SD birth weight was 1549±444 g. There were more small-for-gestational age infants in Malaysian unit: 12/50 (24%) vs UK: 3/50 (6%), p=0.012 and more morbidities. More Malaysian infants received breast milk (Malaysia: 49 (98%) vs UK: 38 (76%), p=0.001), fortified breast milk (Malaysia: 43 (86%) vs UK: 13 (26%), p<0.001) and exclusive breast milk at discharge (Malaysia: 26 (52%) vs UK: 16 (32%), p=0.043). There was higher parenteral nutrition use among Malaysian infants (40/50 (80%)) vs UK (19/50 (38%)) (p<0.001) with higher protein intake (mean±SD Malaysia: 3.0±0.5 vs UK: 2.7±0.6 g/kg/d, p=0.004) in weeks 1-4 and smaller cumulative protein deficits (mean±SD Malaysia: 11.4±6.1 vs UK: 15.4±8.0 g/kg, p=0.006). There were no significant differences in short-term growth between units and more than half of the infants in both units had ≥1.28 changes in weight-for-age Z-score at discharge (p=0.841).
Conclusions: An exploratory comparison of practices showed differences in patient characteristics and nutritional practices which impacted growth. Future studies with larger sample sizes and detailed analysis of maternal characteristics and infants' outcomes are needed for improving care of preterm infants in all settings.
Nano vs Resistant Tuberculosis: Taking the Lung Route

Sharma D, Pooja, Nirban S, Ojha S, Kumar T, Jain N, et al.

AAPS PharmSciTech, 2023 Dec 04;24(8):252.
PMID: 38049695 DOI: 10.1208/s12249-023-02708-3

Tuberculosis (TB) is among the top 10 infectious diseases worldwide. It is categorized among the leading killer diseases that are the reason for the death of millions of people globally. Although a standardized treatment regimen is available, non-adherence to treatment has increased multi-drug resistance (MDR) and extensive drug-resistant (XDR) TB development. Another challenge is targeting the death of TB reservoirs in the alveoli via conventional treatment. TB Drug resistance may emerge as a futuristic restraint of TB with the scarcity of effective Anti-tubercular drugs. The paradigm change towards nano-targeted drug delivery systems is mostly due to the absence of effective therapy and increased TB infection recurrent episodes with MDR. The emerging field of nanotechnology gave an admirable opportunity to combat MDR and XDR via accurate diagnosis with effective treatment. The new strategies targeting the lung via the pulmonary route may overcome the new incidence of MDR and enhance patient compliance. Therefore, this review highlights the importance and recent research on pulmonary drug delivery with nanotechnology along with prevalence, the need for the development of nanotechnology, beneficial aspects of nanomedicine, safety concerns of nanocarriers, and clinical studies.
Fulltext Emergence of taurine as a therapeutic agent for neurological disorders

Jangra A, Gola P, Singh J, Gond P, Ghosh S, Rachamalla M, et al.

Neural Regen Res, 2024 Jan;19(1):62-68.
PMID: 37488845 DOI: 10.4103/1673-5374.374139

Taurine is a sulfur-containing, semi-essential amino acid that occurs naturally in the body. It alternates between inflammation and oxidative stress-mediated injury in various disease models. As part of its limiting functions, taurine also modulates endoplasmic reticulum stress, Ca2+ homeostasis, and neuronal activity at the molecular level. Taurine effectively protects against a number of neurological disorders, including stroke, epilepsy, cerebral ischemia, memory dysfunction, and spinal cord injury. Although various therapies are available, effective management of these disorders remains a global challenge. Approximately 30 million people are affected worldwide. The design of taurine formation could lead to potential drugs/supplements for the health maintenance and treatment of central nervous system disorders. The general neuroprotective effects of taurine and the various possible underlying mechanisms are discussed in this review. This article is a good resource for understanding the general effects of taurine on various diseases. Given the strong evidence for the neuropharmacological efficacy of taurine in various experimental paradigms, it is concluded that this molecule should be considered and further investigated as a potential candidate for neurotherapeutics, with emphasis on mechanism and clinical studies to determine efficacy.
Fulltext Alzheimer's disease-like perturbations in HIV-mediated neuronal dysfunctions: understanding mechanisms and developing therapeutic strategies

Jha NK, Sharma A, Jha SK, Ojha S, Chellappan DK, Gupta G, et al.

Open Biol, 2020 Dec;10(12):200286.
PMID: 33352062 DOI: 10.1098/rsob.200286

Excessive exposure to toxic substances or chemicals in the environment and various pathogens, including viruses and bacteria, is associated with the onset of numerous brain abnormalities. Among them, pathogens, specifically viruses, elicit persistent inflammation that plays a major role in Alzheimer's disease (AD) as well as dementia. AD is the most common brain disorder that affects thought, speech, memory and ability to execute daily routines. It is also manifested by progressive synaptic impairment and neurodegeneration, which eventually leads to dementia following the accumulation of Aβ and hyperphosphorylated Tau. Numerous factors contribute to the pathogenesis of AD, including neuroinflammation associated with pathogens, and specifically viruses. The human immunodeficiency virus (HIV) is often linked with HIV-associated neurocognitive disorders (HAND) following permeation through the blood-brain barrier (BBB) and induction of persistent neuroinflammation. Further, HIV infections also exhibited the ability to modulate numerous AD-associated factors such as BBB regulators, members of stress-related pathways as well as the amyloid and Tau pathways that lead to the formation of amyloid plaques or neurofibrillary tangles accumulation. Studies regarding the role of HIV in HAND and AD are still in infancy, and potential link or mechanism between both is not yet established. Thus, in the present article, we attempt to discuss various molecular mechanisms that contribute to the basic understanding of the role of HIV-associated neuroinflammation in AD and HAND. Further, using numerous growth factors and drugs, we also present possible therapeutic strategies to curb the neuroinflammatory changes and its associated sequels.
Fulltext Bracing NK cell based therapy to relegate pulmonary inflammation in COVID-19

Jeyaraman M, Muthu S, Bapat A, Jain R, Sushmitha ES, Gulati A, et al.

Heliyon, 2021 Jul;7(7):e07635.
PMID: 34312598 DOI: 10.1016/j.heliyon.2021.e07635

The contagiosity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has startled mankind and has brought our lives to a standstill. The treatment focused mainly on repurposed immunomodulatory and antiviral agents along with the availability of a few vaccines for prophylaxis to vanquish COVID-19. This seemingly mandates a deeper understanding of the disease pathogenesis. This necessitates a plausible extrapolation of cell-based therapy to COVID-19 and is regarded equivalently significant. Recently, correlative pieces of clinical evidence reported a robust decline in lymphocyte count in severe COVID-19 patients that suggest dysregulated immune responses as a key element contributing to the pathophysiological alterations. The large granular lymphocytes also known as natural killer (NK) cells play a heterogeneous role in biological functioning wherein their frontline action defends the body against a wide array of infections and tumors. They prominently play a critical role in viral clearance and executing immuno-modulatory activities. Accumulated clinical evidence demonstrate a decrease in the number of NK cells in circulation with or without phenotypical exhaustion. These plausibly contribute to the progression of pulmonary inflammation in COVID-19 pneumonia and result in acute lung injury. In this review, we have outlined the present understanding of the immunological response of NK cells in COVID-19 infection. We have also discussed the possible use of these powerful biological cells as a therapeutic agent in view of preventing immunological harms of SARS-CoV-2 and the current challenges in advocating NK cell therapy for the same.
Fulltext Advances in pulmonary drug delivery targeting microbial biofilms in respiratory diseases

Sharma A, Kumar D, Dahiya K, Hawthorne S, Jha SK, Jha NK, et al.

Nanomedicine (Lond), 2021 09;16(21):1905-1923.
PMID: 34348474 DOI: 10.2217/nnm-2021-0057

The increasing burden of respiratory diseases caused by microbial infections poses an immense threat to global health. This review focuses on the various types of biofilms that affect the respiratory system and cause pulmonary infections, specifically bacterial biofilms. The article also sheds light on the current strategies employed for the treatment of such pulmonary infection-causing biofilms. The potential of nanocarriers as an effective treatment modality for pulmonary infections is discussed, along with the challenges faced during treatment and the measures that may be implemented to overcome these. Understanding the primary approaches of treatment against biofilm infection and applications of drug-delivery systems that employ nanoparticle-based approaches in the disruption of biofilms are of utmost interest which may guide scientists to explore the vistas of biofilm research while determining suitable treatment modalities for pulmonary respiratory infections.
Fulltext Biological databases and tools for neurological disorders

Usman MB, Ojha S, Jha SK, Chellappan DK, Gupta G, Singh SK, et al.

J Integr Neurosci, 2022 Jan 28;21(1):41.
PMID: 35164477 DOI: 10.31083/j.jin2101041

Computational approach to study of neuronal impairment is rapidly evolving, as experiments and intuition alone could not explain the complexity of brain system. The increase in an overwhelming amount of new data from both theory and computational modeling necessitate the development of databases and tools for analysis, visualization, and interpretation of neuroscience data. To ensure the sustainability of this development, consistent update and training of young professionals are imperative. For this purpose, relevant articles, chapters, and modules are essential to keep abreast of developments. Therefore, this article seeks to outline the biological databases and analytical tools along with their applications. It's envisaged that knowledge along this line would be a "training recipe" for young talents and guide for professionals and researchers in neuroscience.
ROCK2 inhibition: A futuristic approach for the management of Alzheimer's disease

Mani S, Jindal D, Chopra H, Jha SK, Singh SK, Ashraf GM, et al.

Neurosci Biobehav Rev, 2022 11;142:104871.
PMID: 36122738 DOI: 10.1016/j.neubiorev.2022.104871

Neurons depend on mitochondrial functions for membrane excitability, neurotransmission, and plasticity. Mitochondrial dynamics are important for neural cell maintenance. To maintain mitochondrial homeostasis, lysosomes remove dysfunctional mitochondria through mitophagy. Mitophagy promotes mitochondrial turnover and prevents the accumulation of dysfunctional mitochondria. In many neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), mitophagy is disrupted in neurons. Mitophagy is regulated by several proteins; recently, Rho-associated coiled-coil containing protein kinase 2 (ROCK2) has been suggested to negatively regulate the Parkin-dependent mitophagy pathway. Thus, ROCK2 inhibition may be a promising therapy for NDDs. This review summarizes the mitophagy pathway, the role of ROCK2 in Parkin-dependent mitophagy regulation, and mitophagy impairment in the pathology of AD. We further discuss different ROCK inhibitors (synthetic drugs, natural compounds, and gene therapy-based approaches) and examine their effects on triggering neuronal growth and neuroprotection in AD and other NDDs. This comprehensive overview of the role of ROCK in mitophagy inhibition provides a possible explanation for the significance of ROCK inhibitors in the therapeutic management of AD and other NDDs.
Fulltext The FBXW7-NOTCH interactome: A ubiquitin proteasomal system-induced crosstalk modulating oncogenic transformation in human tissues

Kar R, Jha SK, Ojha S, Sharma A, Dholpuria S, Raju VSR, et al.

Cancer Rep (Hoboken), 2021 08;4(4):e1369.
PMID: 33822486 DOI: 10.1002/cnr2.1369

BACKGROUND: Ubiquitin ligases or E3 ligases are well programmed to regulate molecular interactions that operate at a post-translational level. Skp, Cullin, F-box containing complex (or SCF complex) is a multidomain E3 ligase known to mediate the degradation of a wide range of proteins through the proteasomal pathway. The three-dimensional domain architecture of SCF family proteins suggests that it operates through a novel and adaptable "super-enzymatic" process that might respond to targeted therapeutic modalities in cancer.
RECENT FINDINGS: Several F-box containing proteins have been characterized either as tumor suppressors (FBXW8, FBXL3, FBXW8, FBXL3, FBXO1, FBXO4, and FBXO18) or as oncogenes (FBXO5, FBXO9, and SKP2). Besides, F-box members like βTrcP1 and βTrcP2, the ones with context-dependent functionality, have also been studied and reported. FBXW7 is a well-studied F-box protein and is a tumor suppressor. FBXW7 regulates the activity of a range of substrates, such as c-Myc, cyclin E, mTOR, c-Jun, NOTCH, myeloid cell leukemia sequence-1 (MCL1), AURKA, NOTCH through the well-known ubiquitin-proteasome system (UPS)-mediated degradation pathway. NOTCH signaling is a primitive pathway that plays a crucial role in maintaining normal tissue homeostasis. FBXW7 regulates NOTCH protein activity by controlling its half-life, thereby maintaining optimum protein levels in tissue. However, aberrations in the FBXW7 or NOTCH expression levels can lead to poor prognosis and detrimental outcomes in patients. Therefore, the FBXW7-NOTCH axis has been a subject of intense study and research over the years, especially around the interactome's role in driving cancer development and progression. Several studies have reported the effect of FBXW7 and NOTCH mutations on normal tissue behavior. The current review attempts to critically analyze these mutations prognostic value in a wide range of tumors. Furthermore, the review summarizes the recent findings pertaining to the FBXW7 and NOTCH interactome and its involvement in phosphorylation-related events, cell cycle, proliferation, apoptosis, and metastasis.
CONCLUSION: The review concludes by positioning FBXW7 as an effective diagnostic marker in tumors and by listing out recent advancements made in cancer therapeutics in identifying protocols targeting the FBXW7-NOTCH aberrations in tumors.
Fulltext Evidence of Coronavirus (CoV) Pathogenesis and Emerging Pathogen SARS-CoV-2 in the Nervous System: A Review on Neurological Impairments and Manifestations

Jha NK, Ojha S, Jha SK, Dureja H, Singh SK, Shukla SD, et al.

J Mol Neurosci, 2021 Nov;71(11):2192-2209.
PMID: 33464535 DOI: 10.1007/s12031-020-01767-6

The coronavirus disease 2019 (COVID-19) pandemic is an issue of global significance that has taken the lives of many across the world. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for its pathogenesis. The pulmonary manifestations of COVID-19 have been well described in the literature. Initially, it was thought to be limited to the respiratory system; however, we now recognize that COVID-19 also affects several other organs, including the nervous system. Two similar human coronaviruses (CoV) that cause severe acute respiratory syndrome (SARS-CoV-1) and Middle East respiratory syndrome (MERS-CoV) are also known to cause disease in the nervous system. The neurological manifestations of SARS-CoV-2 infection are growing rapidly, as evidenced by several reports. There are several mechanisms responsible for such manifestations in the nervous system. For instance, post-infectious immune-mediated processes, direct virus infection of the central nervous system (CNS), and virus-induced hyperinflammatory and hypercoagulable states are commonly involved. Guillain-Barré syndrome (GBS) and its variants, dysfunction of taste and smell, and muscle injury are numerous examples of COVID-19 PNS (peripheral nervous system) disease. Likewise, hemorrhagic and ischemic stroke, encephalitis, meningitis, encephalopathy acute disseminated encephalomyelitis, endothelialitis, and venous sinus thrombosis are some instances of COVID-19 CNS disease. Due to multifactorial and complicated pathogenic mechanisms, COVID-19 poses a large-scale threat to the whole nervous system. A complete understanding of SARS-CoV-2 neurological impairments is still lacking, but our knowledge base is rapidly expanding. Therefore, we anticipate that this comprehensive review will provide valuable insights and facilitate the work of neuroscientists in unfolding different neurological dimensions of COVID-19 and other CoV associated abnormalities.

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