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Fulltext Relation Between Periodontal Status and Pre-Cancerous Condition (Oral Lichen Planus): A Pilot Study

Rai NP, Kumar P, Mustafa SM, Divakar DD, Kheraif AA, Ramakrishnaiah R, et al.

Adv Clin Exp Med, 2016 Jul-Aug;25(4):763-6.
PMID: 27629852 DOI: 10.17219/acem/59014

BACKGROUND: Oral lichen planus (OLP) is a common chronic mucocutaneous disease mostly seen in middle aged and elderly females. Oral lichen planus can occur in different oral sites such as gingiva, labial, buccal mucosa and on the tongue. And can have an indirect effect on initiating periodontitis.
OBJECTIVES: The purpose of the study was to evaluate the periodontal status of OLP patients and compare it with that of healthy controls. The presence of erosive lesions among gingival tissues makes oral hygiene procedures difficult to perform for obvious reasons. Plaque control and rigorous oral hygiene are primary requisites for the treatment of any oro-mucosal disease.
MATERIAL AND METHODS: Thirty patients with the erosive and reticular form of OLP as a study group and 30 healthy subjects as a control group were selected. The periodontal status of all subjects including gingival index (GI), Russell's periodontal index (PI) and bleeding on probing (BOP) were evaluated in both groups. Finally, the data was analyzed by a paired t-test using SPSS software v. 22.
RESULTS: The mean values of GI, PI and BOP were observed to be higher in the study group compared to the control group, and this was statistically significant (p < 0.05). The results shown are suggestive that periodontal status was poor in the study group as compared to the control group.
CONCLUSIONS: Further studies need to investigate periodontal status in oral lichen planus patients with larger sample size, and careful follow-up of these will assure an increase in the quality of life of these patients. The patient should be informed regarding the risk of periodontal problems in OLP and should be advised to have regular dental checkups to avoid a worsening of the conditio.
KEYWORDS: gingivitis; oral lichen planus; periodontitis; pre-cancerous condition
Zingiber officinale attenuates retinal microvascular changes in diabetic rats via anti-inflammatory and antiangiogenic mechanisms

Dongare S, Gupta SK, Mathur R, Saxena R, Mathur S, Agarwal R, et al.

Mol Vis, 2016;22:599-609.
PMID: 27293376

PURPOSE: Diabetic retinopathy is a common microvascular complication of long-standing diabetes. Several complex interconnecting biochemical pathways are activated in response to hyperglycemia. These pathways culminate into proinflammatory and angiogenic effects that bring about structural and functional damage to the retinal vasculature. Since Zingiber officinale (ginger) is known for its anti-inflammatory and antiangiogenic properties, we investigated the effects of its extract standardized to 5% 6-gingerol, the major active constituent of ginger, in attenuating retinal microvascular changes in rats with streptozotocin-induced diabetes.
METHODS: Diabetic rats were treated orally with the vehicle or the ginger extract (75 mg/kg/day) over a period of 24 weeks along with regular monitoring of bodyweight and blood glucose and weekly fundus photography. At the end of the 24-week treatment, the retinas were isolated for histopathological examination under a light microscope, transmission electron microscopy, and determination of the retinal tumor necrosis factor-α (TNF-α), nuclear factor-kappa B (NF-κB), and vascular endothelial growth factor (VEGF) levels.
RESULTS: Oral administration of the ginger extract resulted in significant reduction of hyperglycemia, the diameter of the retinal vessels, and vascular basement membrane thickness. Improvement in the architecture of the retinal vasculature was associated with significantly reduced expression of NF-κB and reduced activity of TNF-α and VEGF in the retinal tissue in the ginger extract-treated group compared to the vehicle-treated group.
CONCLUSIONS: The current study showed that ginger extract containing 5% of 6-gingerol attenuates the retinal microvascular changes in rats with streptozotocin-induced diabetes through anti-inflammatory and antiangiogenic actions. Although precise molecular targets remain to be determined, 6-gingerol seems to be a potential candidate for further investigation.
Brain biometals and Alzheimer's disease - boon or bane?

Prakash A, Dhaliwal GK, Kumar P, Majeed AB

Int J Neurosci, 2017 Feb;127(2):99-108.
PMID: 27044501

Alzheimer's disease (AD) is the most common form of dementia. Several hypotheses have been put forward to explain the basis of disease onset and progression. A complicated array of molecular events has been implicated in the pathogenesis of AD. It is attributed to a variety of pathological conditions that share similar critical processes, such as oxidative stress, proteinaceous aggregations, mitochondrial dysfunctions and energy failure. There is increasing evidence suggesting that metal homeostasis is dysregulated in the pathology of AD. Biometals play an important role in the normal body functioning but AD may be mediated or triggered by disproportion of metal ions leading to changes in critical biological systems and initiating a cascade of events finally leading to neurodegeneration and cell death. The link is multifactorial, and although the source of the shift in oxidative homeostasis is still unclear, current evidence points to changes in the balance of redox transition metals, especially iron, copper (Cu) and other trace metals. Their levels in the brain are found to be elevated in AD. In other neurodegenerative disorders, Cu, zinc, aluminum and manganese are involved. This paper is a review of recent advances of the role of metals in the pathogenesis and pathophysiology of AD and related neurodegenerative diseases.
Granular ameloblastoma: report of two cases with atypical cytological aspects

Arora S, Urs AB, Kumar P, Augustine J, Saran RK

Rom J Morphol Embryol, 2017;58(3):997-1001.
PMID: 29250680

Ameloblastoma is an aggressive odontogenic tumor, which arises from odontogenic epithelium. Ameloblastomas can present in several clinical and histomorphological patterns. The granular cell variant accounts for only 3.5% to 5% of ameloblastomas. We have presented two cases of granular cell ameloblastoma (GCA) occurring in a 44-year-old and 50-year-old man, respectively. Case No. 1 on incisional biopsy was diagnosed as unicystic ameloblastoma (UA), which later after excisional biopsy was finally diagnosed as GCA owing to the features observed in excisional biopsied tissue. Case No. 2 on incisional biopsy showed darker and lighter stained cells arranged in small follicular pattern, and anastomosing cords. Meticulous immunohistochemistry, histochemical examination and careful literature search helped us to diagnose it as GCA. We have made an attempt to elucidate the diagnosis of GCA especially in cases of GCA with unusual granular component.
Piperazine clubbed with 2-azetidinone derivatives suppresses proliferation, migration and induces apoptosis in human cervical cancer HeLa cells through oxidative stress mediated intrinsic mitochondrial pathway

Khanam R, Kumar R, Hejazi II, Shahabuddin S, Meena R, Jayant V, et al.

Apoptosis, 2018 02;23(2):113-131.
PMID: 29349707 DOI: 10.1007/s10495-018-1439-x

Piperazine scaffolds or 2-azetidinone pharmacophores have been reported to show anti-cancer activities and apoptosis induction in different types of cancer cells. However, the mechanistic studies involve in induction of apoptosis addressing these two moieties for human cervical cancer cells remain uncertain. The present study emphasizes on the anti-proliferating properties and mechanism involved in induction of apoptosis for these structurally related azoles derivatives in HeLa cancer cells. 1-Phenylpiperazine clubbed with 2-azetidione derivatives (5a-5h) were synthesized, characterized using various spectroscopic techniques and evaluated for their in-vitro anti-proliferative activities and induction of apoptosis. Further, we also evaluated oxidative stress generated by these synthetic derivatives (5a-5h). Cell viability studies revealed that among all, the compound N-(3-chloro-2-(3-nitrophenyl)-4-oxoazetidin-1-yl)-2-(4-phenylpiperazin-1-yl) acetamide 5e remarkably inhibited the growth of HeLa cells in a concentration dependent manner having IC50 value of 29.44 ± 1.46 µg/ml. Morphological changes, colonies suppression and inhibition of migration clearly showed the antineoplasicity in HeLa cells treated with 5e. Simultaneously, phosphatidylserine externalization, DNA fragmentation and cell-cycle arrest showed ongoing apoptosis in the HeLa cancer cells induced by compound 5e in concentration dependent manner. Additionally, generation of intracellular ROS along with the decrease in mitochondrial membrane potential supported that compound 5e caused oxidative stress resulting in apoptosis through mitochondria mediated pathway. Elevation in the level of cytochrome c and upregulation in expression of caspase-3 clearly indicated the involvement of the intrinsic pathway of programmed cell death. In brief; compound 5e could serve as a promising lead for the development of an effective antitumor agent.
Anthropometric and Anthroposcopic Analysis of Periorbital Features in Malaysian Population: An Inter-racial Study

Packiriswamy V, Kumar P, Bashour M

Facial Plast Surg, 2018 Aug;34(4):400-406.
PMID: 29723879 DOI: 10.1055/s-0038-1648224

In oculoplastic operations, knowledge of the dimensions of periorbital features based on age, gender, and race is essential for achieving better aesthetic result. This article seeks to determine the racial and gender differences of periorbital features among Malaysian Malay (MM), Malaysian Indian (MI), and Malaysian Chinese (MI) subjects. Evaluation of periorbital features was done on photographs of 200 MM, 200 MI, and 200 MC subjects, aged 18 to 26 years. The measured values were evaluated by an independent t-test. A significant difference was found between MM and MI in all measurements except interbrow distance in males, eyebrow thickness in females, and apex to lateral limbus distance in both sexes. Between MI and MC the difference was insignificant for interbrow distance in male groups, apex to lateral limbus distance in females, and palpebral fissure inclination and eyebrow apex angle in both sexes. Between MM and MC, significant differences were found for eyebrow thickness and medial canthus tilt in female group. Male groups showed significant difference for apex to lateral limbus and lateral canthus distance and eyebrow apex angle. Eyebrow height, palpebral fissure width, and intercanthal distance were significantly different in both sexes. Sexual dimorphism was found for all measurements in MI, but MM and MC showed insignificant difference for eyebrow apex angle. Four types of epicanthus were observed in MM and MC and three types in MI. Eyebrow apex between lateral limbus and lateral canthus was the most common position in all racial groups. Significant racial and gender differences exist for certain periorbital measurements. The knowledge of these differences is expected to influence the surgical outcome.
Fulltext Proteomic Analysis of the Human Anterior Pituitary Gland

Yelamanchi SD, Tyagi A, Mohanty V, Dutta P, Korbonits M, Chavan S, et al.

OMICS, 2018 12;22(12):759-769.
PMID: 30571610 DOI: 10.1089/omi.2018.0160

The pituitary function is regulated by a complex system involving the hypothalamus and biological networks within the pituitary. Although the hormones secreted from the pituitary have been well studied, comprehensive analyses of the pituitary proteome are limited. Pituitary proteomics is a field of postgenomic research that is crucial to understand human health and pituitary diseases. In this context, we report here a systematic proteomic profiling of human anterior pituitary gland (adenohypophysis) using high-resolution Fourier transform mass spectrometry. A total of 2164 proteins were identified in this study, of which 105 proteins were identified for the first time compared with high-throughput proteomic-based studies from human pituitary glands. In addition, we identified 480 proteins with secretory potential and 187 N-terminally acetylated proteins. These are the first region-specific data that could serve as a vital resource for further investigations on the physiological role of the human anterior pituitary glands and the proteins secreted by them. We anticipate that the identification of previously unknown proteins in the present study will accelerate biomedical research to decipher their role in functioning of the human anterior pituitary gland and associated human diseases.
Assessing the potential of liposomes loaded with curcumin as a therapeutic intervention in asthma

Ng ZY, Wong JY, Panneerselvam J, Madheswaran T, Kumar P, Pillay V, et al.

Colloids Surf B Biointerfaces, 2018 Dec 01;172:51-59.
PMID: 30134219 DOI: 10.1016/j.colsurfb.2018.08.027

Curcumin a component of turmeric, which is derived from Curcuma longa is used as a colouring agent and as a dietary spice for centuries. Extensive studies have been done on the anti-inflammatory activity of curcumin along with its molecular mechanism involving different signalling pathways. However, the physicochemical and biological properties such as poor solubility and rapid metabolism of curcumin have led to low bioavailability and hence limits its application. Current therapies for asthma such as bronchodilators and inhaled corticosteroids (ICS) are aimed at controlling disease symptoms and prevent asthma exacerbation. However, this approach requires lifetime therapy and is associated with a constellation of side effects. This creates a clear unmet medical need and there is an urgent demand for new and more-effective treatments. The present study is aimed to formulate liposomes containing curcumin and evaluate for its anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation on BCi-NS1.1 cell line. Curcumin and salbutamol liposomes were formulated using lipid hydration method. The prepared liposomes were characterized in terms of particle size, zeta potential, encapsulation efficiency and in-vitro release profile. The liposomes were tested on BCI-NS1.1 cell line to evaluate its anti-inflammatory properties. The various pro-inflammatory markers studied were Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-1β (IL-1β) and Tumour Necrosis Factor-a (TNF-a). Additionally, molecular mechanics simulations were used to elucidate the positioning, energy minimization, and aqueous dispersion of the liposomal architecture involving lecithin and curcumin. The prepared curcumin formulation showed an average size and zeta potential of 271.3 ± 3.06 nm and -61.0 mV, respectively. The drug encapsulation efficiency of liposomal curcumin is 81.1%. Both curcumin-loaded liposomes formulation (1 μg/mL, 5 μg/mL) resulted in significant (p
A new record of the genus Orientalicesa Koçak Kemal, 2010 (Hymenoptera: Vespidae: Eumeninae) from Vietnam

Nguyen LTP, BozdoĞan H, Kumar PG, Carpenter JM

Zootaxa, 2018 Dec 20;4532(4):594-596.
PMID: 30647350 DOI: 10.11646/zootaxa.4532.4.9

The genus Orientalicesa has six species, and all of them have been recorded in the Oriental region (including Indonesia, Malaysia, Phillippines, Laos, China). In this paper, the genus Orientalicesa is newly recorded from Vietnam, represented by one species O. confasciatus Tan and Carpenter. This species was mistakenly redescribed as Stenodyneriellus rangpocus Kumar, Carpenter Kishore, 2017. A new synonym of O. confasciatus is proposed, and that species is a new record for India.
Indoor air quality-induced respiratory symptoms of a hospital staff in Iran

Veysi R, Heibati B, Jahangiri M, Kumar P, Latif MT, Karimi A

Environ Monit Assess, 2019 Jan 05;191(2):50.
PMID: 30612195 DOI: 10.1007/s10661-018-7182-5

The ambient air of hospitals contains a wide range of biological and chemical pollutants. Exposure to these indoor pollutants can be hazardous to the health of hospital staff. This study aims to evaluate the factors affecting indoor air quality and their effect on the respiratory health of staff members in a busy Iranian hospital. We surveyed 226 hospital staff as a case group and 222 office staff as a control group. All the subjects were asked to fill in a standard respiratory questionnaire. Pulmonary function parameters were simultaneously measured via a spirometry test. Environmental measurements of bio-aerosols, particulate matter, and volatile organic compounds in the hospital and offices were conducted. T-tests, chi-square tests, and multivariable logistic regressions were used to analyze the data. The concentration of selected air pollutants measured in the hospital wards was more than those in the administrative wards. Parameters of pulmonary functions were not statistically significant (p > 0.05) between the two groups. However, respiratory symptoms such as coughs, phlegm, phlegmatic coughs, and wheezing were more prevalent among the hospital staff. Laboratory staff members were more at risk of respiratory symptoms compared to other occupational groups in the hospital. The prevalence of sputum among nurses was significant, and the odds ratio for the presence of phlegm among nurses was 4.61 times greater than office staff (p = 0.002). The accumulation of indoor pollutants in the hospital environment revealed the failure of hospital ventilation systems. Hence, the design and implementation of an improved ventilation system in the studied hospital is recommended.
Airborne particles in the city center of Kuala Lumpur: Origin, potential driving factors, and deposition flux in human respiratory airways

Khan MF, Hamid AH, Bari MA, Tajudin ABA, Latif MT, Nadzir MSM, et al.

Sci Total Environ, 2019 Feb 10;650(Pt 1):1195-1206.
PMID: 30308807 DOI: 10.1016/j.scitotenv.2018.09.072

Equatorial warming conditions in urban areas can influence the particle number concentrations (PNCs), but studies assessing such factors are limited. The aim of this study was to evaluate the level of size-resolved PNCs, their potential deposition rate in the human respiratory system, and probable local and transboundary inputs of PNCs in Kuala Lumpur. Particle size distributions of a 0.34 to 9.02 μm optical-equivalent size range were monitored at a frequency of 60 s between December 2016 and January 2017 using an optical-based compact scanning mobility particle sizer (SMPS). Diurnal and correlation analysis showed that traffic emissions and meteorological confounding factors were potential driving factors for changes in the PNCs (Dp ≤1 μm) at the modeling site. Trajectory modeling showed that a PNC <100/cm3 was influenced mainly by Indo-China region air masses. On the other hand, a PNC >100/cm3 was influenced by air masses originating from the Indian Ocean and Indochina regions. Receptor models extracted five potential sources of PNCs: industrial emissions, transportation, aged traffic emissions, miscellaneous sources, and a source of secondary origin coupled with meteorological factors. A respiratory deposition model for male and female receptors predicted that the deposition flux of PM1 (particle mass ≤1 μm) into the alveolar (AL) region was higher (0.30 and 0.25 μg/h, respectively) than the upper airway (UA) (0.29 and 0.24 μg/h, respectively) and tracheobronchial (TB) regions (0.02 μg/h for each). However, the PM2.5 deposition flux was higher in the UA (2.02 and 1.68 μg/h, respectively) than in the TB (0.18 and 0.15 μg/h, respectively) and the AL regions (1.09 and 0.91 μg/h, respectively); a similar pattern was also observed for PM10.
Influenza A virus neuraminidase protein interacts with Hsp90, to stabilize itself and enhance cell survival

Kumar P, Gaur P, Kumari R, Lal SK

J Cell Biochem, 2019 04;120(4):6449-6458.
PMID: 30335904 DOI: 10.1002/jcb.27935

Neuraminidase protein (NA) of influenza A virus (IAV) is popularly known for its sialidase function to assist in the release of progeny virus. However, involvement of NA in other stages of the IAV life cycle also indicates its multifunctional nature and necessity to interact with other host proteins. Here, we report a host protein-heat shock protein 90 (Hsp90), as a novel interacting partner of IAV NA. A classical yeast two-hybrid screen was conducted to identify a new host interacting partner for NA and the interaction was further validated by coimmunoprecipitation from cells, transiently expressing both proteins and also from IAV-infected cells. Confocal imaging showed that both proteins colocalized in the cytoplasm in transfected host cells. Interestingly, increased levels of NA in the presence of Hsp90 was observed, which tends to decrease if adenosine triphosphatase activity of Hsp90 is inhibited using 17-N-allylamino-17-demethoxygeldanamycin (17AAG). This establishes viral NA as a client protein of host chaperone Hsp90 contributing toward NA's stability via the NA-Hsp90 interaction. This is the first report showing the interaction of NA with Hsp90 and its role in stabilizing viral NA thus preventing it from degradation. Enhanced cell survival in the presence of this interaction was also observed, thus suggesting the requirement of stable viral NA, post-IAV infection, for efficient virus production in infected mammalian cells.
Fulltext Mapping 123 million neonatal, infant and child deaths between 2000 and 2017

Burstein R, Henry NJ, Collison ML, Marczak LB, Sligar A, Watson S, et al.

Nature, 2019 Oct;574(7778):353-358.
PMID: 31619795 DOI: 10.1038/s41586-019-1545-0

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2-to end preventable child deaths by 2030-we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000-2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations.
Direct cell imprint lithography in superconductive carbon black polymer composites: process optimization, characterization and in vitro toxicity analysis

Narayanamurthy V, Samsuri F, Firus Khan AY, Hamzah HA, Baharom MB, Kumary TV, et al.

Bioinspir Biomim, 2019 11 06;15(1):016002.
PMID: 30897554 DOI: 10.1088/1748-3190/ab1243

Cell imprint lithography (CIL) or cell replication plays a vital role in fields like biomimetic smart culture substrates, bone tissue engineering, cell guiding, cell adhesion, tissue engineering, cell microenvironments, tissue microenvironments, cell research, drug delivery, diagnostics, therapeutics and many other applications. Herein we report a new formulation of superconductive carbon black photopolymer composite and its characterization towards a CIL process technique. In this article, we demonstrated an approach of using a carbon nanoparticle-polymer composite (CPC) for patterning cells. It is observed that a 0.3 wt % load of carbon nanoparticles (CNPs) in a carbon polymer mixture (CPM) was optimal for cell-imprint replica fabrication. The electrical resistance of the 3-CPC (0.3 wt %) was reduced by 68% when compared to N-CPC (0 wt %). This method successfully replicated the single cell with sub-organelle scale. The shape of microvesicles, grooves, pores, blebs or microvilli on the cellular surface was patterned clearly. This technique delivers a free-standing cell feature substrate. In vitro evaluation of the polymer demonstrated it as an ideal candidate for biomimetic biomaterial applications. This approach also finds its application in study based on morphology, especially for drug delivery applications and for investigations based on molecular pathways.
Ratio Analysis Evaluation of Dermal Collagen and Elastic Fiber Contents: A Comparison of the Horizontal and Vertical Directions of Skin Tissues

Kumar N, Kumar P, Nayak B S, Aithal P A, Guru A

J Clin Aesthet Dermatol, 2019 Dec;12(12):21-24.
PMID: 32038760

Background: Stretching force on the skin leads to the widening of scars and/or hypertrophy. The uneven distribution profile of collagen and elastic fibers in the human dermis (evaluated based on their topographic areas) might determine the direction of incision for a more pleasing aesthetic result. Materials and methods: Full-thickness skin samples were collected in the horizontal and vertical directions from 15 areas of 32 human cadavers. The histological preparation of the skin samples was performed using special Verhoeff-van Gieson staining. Image analysis in the TissueQuant software was performed using photomicrographs. Quantitative fraction measures for collagen and elastic fibers were completed. From the data obtained, various ratios between collagen in the horizontal (CH) and vertical (CV) directions and elastic fibers in the horizontal (EH) and vertical (EV) directions were established and expressed as CH:CV and EH:EV. Results: In the areas where CV:CH was less than 1 (low ratio of significance), the collagen content was significantly higher in the horizontal direction than the vertical direction (CH>CV). However, this finding is reversed (CV>CH) in areas where CV:CH is greater than 1 (high ratio of significance). Similarly, in areas where EV:EH is less than 1 (low ratio of significance), the elastic fiber content was significantly higher in the horizontal direction than the vertical direction (EH>EV), whereas such is reversed (EV>EH) where EV:EH is greater than 1 (high ratio of significance). Conclusion: The evaluation of ratios of dermal collagen and elastic fibers in different directions together with the data of asymmetric distribution provide a useful guideline for aesthetic surgeons looking to place elective incisions in the direction that will ensure an improved aesthetically pleasing result.
Fulltext Standardised neonatal parenteral nutrition formulations - Australasian neonatal parenteral nutrition consensus update 2017

Bolisetty S, Osborn D, Schindler T, Sinn J, Deshpande G, Wong CS, et al.

BMC Pediatr, 2020 02 08;20(1):59.
PMID: 32035481 DOI: 10.1186/s12887-020-1958-9

BACKGROUND: The first consensus standardised neonatal parenteral nutrition formulations were implemented in many neonatal units in Australia in 2012. The current update involving 49 units from Australia, New Zealand, Singapore, Malaysia and India was conducted between September 2015 and December 2017 with the aim to review and update the 2012 formulations and guidelines.
METHODS: A systematic review of available evidence for each parenteral nutrient was undertaken and new standardised formulations and guidelines were developed.
RESULTS: Five existing preterm Amino acid-Dextrose formulations have been modified and two new concentrated Amino acid-Dextrose formulations added to optimise amino acid and nutrient intake according to gestation. Organic phosphate has replaced inorganic phosphate allowing for an increase in calcium and phosphate content, and acetate reduced. Lipid emulsions are unchanged, with both SMOFlipid (Fresenius Kabi, Australia) and ClinOleic (Baxter Healthcare, Australia) preparations included. The physicochemical compatibility and stability of all formulations have been tested and confirmed. Guidelines to standardise the parenteral nutrition clinical practice across facilities have also been developed.
CONCLUSIONS: The 2017 PN formulations and guidelines developed by the 2017 Neonatal Parenteral Nutrition Consensus Group offer concise and practical instructions to clinicians on how to implement current and up-to-date evidence based PN to the NICU population.
Erlotinib-loaded carboxymethyl temarind gum semi-interpenetrating nanocomposites

Bera H, Abbasi YF, Lee Ping L, Marbaniang D, Mazumder B, Kumar P, et al.

Carbohydr Polym, 2020 Feb 15;230:115664.
PMID: 31887927 DOI: 10.1016/j.carbpol.2019.115664

Erlotinib-loaded carboxymethyl temarind gum-g-poly(N-isopropylacrylamide)-montmorillonite based semi-IPN nanocomposites were synthesized and characterized for their in vitro performances for lung cancer therapy. The placebo matrices exhibited outstanding biodegradability and pH-dependent swelling profiles. The molar mass (M¯ c) between the crosslinks of these composites was declined with temperature. The solid state characterization confirmed the semi-IPN architecture of these scaffolds. The corresponding drug-loaded formulations displayed excellent drug-trapping capacity (DEE, 86-97 %) with acceptable zeta potential (-16 to -13 mV) and diameter (967-646 nm). These formulations conferred sustained drug elution profiles (Q8h, 77-99 %) with an initial burst release. The drug release profile of the optimized formulation (F-3) was best fitted in the first order kinetic model with Fickian diffusion driven mechanism. The mucin adsorption to F-3 followed Langmuir isotherms. The results of MTT assay, AO/EB staining and confocal analyses revealed that the ERL-loaded formulation suppressed A549 cell proliferation and induced apoptosis more effectively than pristine drug.
Analytical and computational sliding wear prediction in a novel knee implant: a case study

Hussin MS, Fernandez J, Ramezani M, Kumar P, Kelly PA

Comput Methods Biomech Biomed Engin, 2020 Mar;23(4):143-154.
PMID: 31928215 DOI: 10.1080/10255842.2019.1709118

Osteoarthritis (OA) is a commonly occurring cartilage degenerative disease. The end stage treatment is Total Knee Arthroplasty (TKA), which can be costly in terms of initial surgery, but also in terms of revision knee arthroplasty, which is quite often required. A novel conceptual knee implant has been proposed to function as a reducer of stress across the joint surface, to extend the period of time before TKA becomes necessary. The objective of this paper is to develop a computational model which can be used to assess the wear arising at the implant articulating surfaces. Experimental wear coefficients were determined from physical testing, the results of which were verified using a semi-analytical model. Experimental results were incorporated into an anatomically correct computational model of the knee and implant. The wear-rate predicted for the implant was 27.74 mm3 per million cycles (MC) and the wear depth predicted was 1.085 mm/MC. Whereas the wear-rate is comparable to that seen in conventional knee implants, the wear depth is significantly higher than for conventional knee prostheses, and indicates that, in order to be viable, wear-rates should be reduced in some way, perhaps by using low-wear polymers.
AML1 protein interacts with influenza A virus neuraminidase and upregulates IFN-β response in infected mammalian cells

Gaur P, Kumar P, Sharma A, Lal SK

Lett Appl Microbiol, 2020 Apr;70(4):252-258.
PMID: 31990997 DOI: 10.1111/lam.13279

Neuraminidase (NA) is an integral membrane protein of influenza A virus (IAV) and primarily aids in the release of progeny virions, following the intracellular viral replication cycle. In an attempt to discover new functions of NA, we conducted a classical yeast two-hybrid screen and found acute myeloid leukaemia marker 1 (AML1) as a novel interacting partner of IAV-NA. The interaction was further validated by co-immunoprecipitation in IAV-infected cells and in an in vitro coupled transcription/translation system. Interestingly, we found an increase in the expression of AML1 upon IAV infection in a dose-dependent manner. As expected, we also observed an increase in the IFN-β levels, the first line of defence against viral infections. Subsequently, when AML1 was downregulated using siRNA, the IFN-β levels were found to be remarkably reduced. Our study also shows that AML1 is induced upon IAV infection and results in the induction of IFN-β. Thus, AML1 is proposed to be an important player in IFN induction and has a role in an antiviral response against IAV infection. SIGNIFICANCE AND IMPACT OF THE STUDY: Influenza epidemics and pandemics are constant threats to human health. Development of antiviral therapeutics has focused on important and major IAV proteins as targets. However, the rate at which this virus mutates makes the task challenging. Thus, next-generation approaches aim at host cellular proteins that aid the virus in its replication. This study reports a new host-virus interaction, of acute myeloid leukaemia marker 1 (AML1) with influenza A neuraminidase (IAV-NA). We have found that this interaction has a direct effect on the upregulation of host IFN-β response. Further studies may lead to a greater understanding of this new innate defence pathway in infected cells.
Fulltext Upregulation of miR-101 during Influenza A Virus Infection Abrogates Viral Life Cycle by Targeting mTOR Pathway

Sharma S, Chatterjee A, Kumar P, Lal S, Kondabagil K

Viruses, 2020 04 15;12(4).
PMID: 32326380 DOI: 10.3390/v12040444

Micro RNAs (miRNAs) are a class of small non-coding single-stranded RNA, which play an important role in modulating host-Influenza A virus (IAV) crosstalk. The interplay between influenza and miRNA interaction is defined by a plethora of complex mechanisms, which are not fully understood yet. Here, we demonstrate that in IAV infected A549 cells, a synchronous increase was observed in the expression of mTOR up to 24 hpi and significant downregulation at 48 hpi. Additionally, NP of IAV interacts with mTOR and modulates the levels of mTOR mRNA and protein, thus regulating the translation of host cell. RNA sequencing and qPCR analysis of IAV-infected A549 cells and NP transfected cells revealed that miR-101 downregulates mTOR transcripts at later stages of infection. Ectopic expression of miR-101 mimic led to a decrease in expression of NP, a reduction in IAV titer and replication. Moreover, treatment of the cells with Everolimus, a potent inhibitor of mTOR, resulted in an increase of miR-101 transcript levels, which further suppressed the viral protein synthesis. Collectively, the data suggest a novel mechanism that IAV stimulates mTOR pathway at early stages of infection; however, at a later time-point, positive regulation of miR-101 restrains the mTOR expression, and hence, the viral propagation.

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