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Abstract Physical properties of biomolecular condensates formed via phase separation of proteins and nucleic acids are associated with cell physiology and disease. Condensate properties can be regulated by several cellular factors including post-translational modifications. Here, we introduce an application of intermolecular energy migration via homo-FRET (Förster resonance energy transfer), a nanometric proximity ruler, to study the modulation in short- and long-range protein-protein interactions leading to the changes in the physical properties of condensates of fluorescently-tagged FUS (Fused in Sarcoma) that is associated with the formation of cytoplasmic and nuclear membraneless organelles. We show that homoFRET captures modulations in condensate properties of FUS by RNA, ATP, and post-translational arginine methylation. We also extend the homoFRET methodology to study the in-situ formation of cytoplasmic stress granules in mammalian cells. Our studies highlight the broad applicability of homoFRET as a potent generic tool for studying intracellular phase transitions involved in function and disease.

A series of Isatin thiosemicarbazones and their copper(II) complexes were synthesized and evaluated for their anti-cancer activities to develop potent chemotherapeutic agents. Among the compounds synthesized, copper conjugated isatin-thiosemicarbazone derivative, Cu-Istpypz, showed considerable anti-proliferative activity against A431 (Skin Cancer) and A549 (Lung Cancer) cell lines. Cell viability assay using crystal violet dye exhibited the effects of the compounds against those cell lines. Cu-Istpypz was highly effective in inhibiting A431 cell proliferation at lower concentrations. The compound Cu-Istpypz also suppressed the colony formation of A431 cells in a concentration-dependent manner, as demonstrated by the clonogenic assay. Additionally, at higher concentrations, Cu-Istpypz slowed down the migration and wound-healing capabilities of A431 cells. RT-PCR and western blot analysis indicated that the compound induced the expression of pro-apoptotic Bax and inhibited anti-apoptotic Bcl-2 and Bcl-xl in a concentration-dependent manner. Further, the compound induces intrinsic apoptosis in A431 cells by activating the JNK signalling pathway and suppressing the PI3K/AKT pathway. DNA fragmentation assay further confirms the onset of apoptosis in the presence of the compound. All these confirm that Cu-Istpypz thiosemicarbazone has the potential to be developed as a future chemotherapeutic agent in the treatment of skin cancer.

Obesity is an enormous global health problem, and obesity‐induced nonalcoholic steatohepatitis (NASH) is contributing to a rising incidence and mortality for hepatocellular carcinoma (HCC). Increase in de novo lipogenesis and decrease in fatty acid β‐oxidation (FAO) underlie hepatic lipid accumulation in NASH. Astrocyte‐elevated gene‐1/metadherin (AEG‐1) overexpression contributes to both NASH and HCC. AEG‐1 harbors an LXXLL motif through which it blocks activation of peroxisome proliferator activated receptor α (PPARα), a key regulator of FAO. To better understand the role of LXXLL motif in mediating AEG‐1 function, using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology, we generated a mouse model (AEG‐1‐L24K/L25H) in which the LXXLL motif in AEG‐1 was mutated to LXXKH. We observed increased activation of PPARα in AEG‐1‐L24K/L25H livers providing partial protection from high‐fat diet–induced steatosis. Interestingly, even with equal gene dosage levels, compared with AEG‐1–wild‐type livers, AEG‐1‐L24K/L25H livers exhibited increase in levels of lipogenic enzymes, mitogenic activity and inflammation, which are attributes observed when AEG‐1 is overexpressed. These findings indicate that while LXXLL motif favors steatotic activity of AEG‐1, it keeps in check inflammatory and oncogenic functions, thus maintaining a homeostasis in AEG‐1 function. AEG‐1 is being increasingly appreciated as a viable target for ameliorating NASH and NASH‐HCC, and as such, in‐depth understanding of the functions and molecular attributes of this molecule is essential. Conclusion: The present study unravels the unique role of the LXXLL motif in mediating the balance between the metabolic and oncogenic functions of AEG‐1.

Rapid evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV) poses enormous challenge in the development of broad-spectrum antivirals that are effective against the existing and emerging viral strains. Virus entry through endocytosis represents an attractive target for drug development, as inhibition of this early infection step should block downstream infection processes, and potentially inhibit viruses sharing the same entry route. In this study, we report the identification of 1,3-diphenylurea (DPU) derivatives (DPUDs) as a new class of endocytosis inhibitors, which broadly restricted entry and replication of several SARS-CoV-2 and IAV strains. Importantly, the DPUDs did not induce any significant cytotoxicity at concentrations effective against the viral infections. Examining the uptake of cargoes specific to different endocytic pathways, we found that DPUDs majorly affected clathrin-mediated endocytosis, which both SARS-CoV-2 and IAV utilize for cellular entry. In the DPUD-treated cells, although virus binding on the cell surface was unaffected, internalization of both the viruses was drastically reduced. Since compounds similar to the DPUDs were previously reported to transport anions including chloride (Cl-) across lipid membrane and since intracellular Cl- concentration plays a critical role in regulating vesicular trafficking, we hypothesized that the observed defect in endocytosis by the DPUDs could be due to altered Cl- gradient across the cell membrane. Using in vitro assays we demonstrated that the DPUDs transported Cl- into the cell and led to intracellular Cl- accumulation, which possibly affected the endocytic machinery by perturbing intracellular Cl- homeostasis. Finally, we tested the DPUDs in mice challenged with IAV and mouse-adapted SARS-CoV-2 (MA 10). Treatment of the infected mice with the DPUDs led to remarkable body weight recovery, improved survival and significantly reduced lung viral load, highlighting their potential for development as broad-spectrum antivirals.

In this study, nanocomposite film was fabricated using cellulose nanocrystals (CNCs) as nanofiller in a polymer matrix of polyvinyl alcohol (PVA) and gum tragacanth (GT) via solution casting. CNCs were extracted from sugarcane bagasse using a steam explosion technique followed by acid hydrolysis. Initial analysis of CNCs by transmission electron microscopy (TEM) showed nanosized particles of 104 nm in length and 7 nm in width. Physical and chemical characteristics of neat PVA, PVA/GT, and PVA/GT/CNC films with varying concentrations of CNCs (from 2% to 10%) were analyzed by the scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectrometry, mechanical test, and swelling test. The SEM analysis showed cluster formation of CNCs in the polymer matrix at high concentration. The developed films were transparent. FTIR spectrometry analysis confirmed the chemical functional groups of the various components in the film. The presence of GT and CNCs in the polymer matrix improved the characteristics of films as evident in the prolonged stability for 7 days and increased mechanical properties. The highest elastic modulus of 1526.11 ± 31.86 MPa and tensile strength of 80.39 MPa were recorded in PVA/GT/CNC2 film. The swelling ability, however, decreased from 260% to 230%. Cytotoxicity analysis of the PVA/GT/CNC film showed that it is nontoxic to mouse fibroblast cells L929 with 95% cell viability. Films loaded with betel leaf extract exhibited excellent antibacterial activities against Staphylococcus aureus DMST 8840 and Pseudomonas aeruginosa TISTR 781 with 28.20 ± 0.84 mm and 23.60 ± 0.55 mm inhibition zones, respectively. These results demonstrate that PVA/GT/CNC loaded with the betel leaf extract could act as promising and versatile wound dressings to protect the wound surface from infection and dehydration.

High-content screening prompted the development of software enabling discrete phenotypic analysis of single cells. Here, the authors show that supervised continuous machine learning can drive novel discoveries in diverse imaging experiments and present the Regression Plane module of Advanced Cell Classifier.

Herein, we report the synthesis of novel worm like structured SnO2 nanoparticles photocatalysts by chemical precipitation route from sodium stannate in the absence of a precipitating agent. The physico-chemical characteristics of the synthesized SnO2 were studied using powder X-ray diffraction (PXRD), Diffuse Reflectance Spectroscopy (DRS), Photoluminescence (PL), and High resolution transmission electron microscope (HRTEM) studies. PXRD and HRTEM analysis reveals the formation of amorphous SnO2 in the tetragonal crystal structure. XPS and PL characterization affirmed the presence of oxygen defects in SnO2, which could be due to Sn2+ present in the lattices. The optical band gap calculated using Kubelka-Munk method to be 3.8 eV. Photocatalytic studies of the prepared SnO2 catalyst showed 92% of Rhodamine-B (RhB) degradation in 120 min under UV irradiation. The enhanced dye degradation activity is attributed to oxygen defects in the SnO2 catalyst, which are responsible for the enhanced charge separation and inhibition of electron-hole pair recombination by trapping photogenerated electrons.

Red Blood Cells (RBCs)-derived particles are an emerging group of novel drug delivery systems. The natural attributes of RBCs make them potential candidates for use as a drug carrier or nanoparticle camouflaging material as they are innately biocompatible. RBCs have been studied for multiple decades in drug delivery applications but their evolution in the clinical arena are considerably slower. They have been garnering attention for the unique capability of conserving their membrane proteins post fabrication that help them to stay non-immunogenic in the biological environment prolonging their circulation time and improving therapeutic efficiency. In this review, we discuss about the synthesis, significance, and various biomedical applications of the above-mentioned classes of engineered RBCs. This article is focused on the current state of clinical translation and the analysis of the hindrances associated with the transition from lab to clinic applications.

Scientists are concerned about the health risks associated with consuming a diet high in saturated fats. In this regard, oleogels have been used as a shortening substitute by researchers. This present study evaluated the role of stearyl alcohol (SA)-, and Span-60 (SP)-tailored sunflower wax/sunflower oil oleogels upon butter replacement in whole wheat batter and cake. The evaluation of the cake batter under PLM microscopy revealed that a complete replacement of butter with SA-containing oleogels, i.e., Sa-C, showed homogenously distributed smaller gas cells. A uniform distribution of gas cells assists in stabilization and contributes to the porosity of the cake. The DSC and FTIR studies confirmed the prominent melting of amylose-lipid complexes in batter Sa-C. The baked cake Sa-C showed the existence of large pores in the cake matrix, which may have assisted in softening the cake. Further, low starch–lipid interactions were also observed in the FTIR spectra of Sa-C cake crumbs. The SR studies of cake crumbs revealed a higher stress-relaxing ability in Sa-C from the control. Although there were no observed variations in the cake hardness values, Sa-C showed a reduction in the chewiness from the control. This current study suggests the possibility of using emulsifier-tailored oleogels as a potential substitute for butter in the baking formulation.

A rising health concern with saturated fatty acids allowed researchers to look into the science of replacing these fats with unsaturated fatty acids. Oleogelation is a technique to structure edible oil using gelators. The present study looked for the effect of solid emulsifiers; namely, sorbitan monostearate (SP) and stearyl alcohol (SA), on the physicochemical parameters of oleogels. All the oleogels were formulated using 5% sunflower wax (SW) in sunflower oil (SO). The formulated oleogels displayed irregular-shaped wax crystals on their surface. The bright-field and polarized microscopy showed the fiber/needle network of wax crystals. Formulations consisting of 10 mg (0.05% w/w) of both the emulsifiers (SA10 and SP10) in 20 g of oleogels displayed the appearance of a dense wax crystal network. The SP and SA underwent co-crystallization with wax molecules, which enhanced crystal growth and increased the density and size of the wax crystals. The XRD and FTIR studies suggested the presence of a similar β’ polymorph to that of the triacylglycerols’ arrangement. The incorporation of SA and SP in wax crystal packing might have resulted in a lower crystallization rate in SA10 and SP10. Evaluation of the thermal properties of oleogels through DSC showed better gel recurrence of high melting enthalpy. These formulations also displayed a sustained release of curcumin. Despite the variations in several properties (e.g., microstructures, crystallite size, thermal properties, and nutrient release), the emulsifiers did not affect the mechanical properties of the oleogel. The meager amounts of both the emulsifiers were able to modulate the nutrient release from the oleogels without affecting their mechanical properties in comparison to the control sample.

Isolated fallopian tube torsion is an extremely rare occurrence in a young female. The lady concerned presented with acute abdominal pain and the ovaries were normal on the scan with dilated fallopian tubes. On laparoscopy, it was revealed that she was suffering from fallopian tube torsion and laparoscopic salpingectomy was performed. The patient recovered well postoperatively.

There is a pressing need for a ubiquitously expressed antigen or receptor on the tumor surface for successful mitigation of the deleterious side effects of chemotherapy. Phosphatidylserine (PS), normally constrained to the intracellular surface, is exposed on the external surface of tumors and most tumorigenic cell lines. Here we report that a novel PS-targeting liposome, phosphatidylcholine-stearylamine (PC-SA), induced apoptosis and showed potent anticancer effects as a single agent against a majority of cancer cell lines. We experimentally proved that this was due to a strong affinity for and direct interaction of these liposomes with PS. Complexation of the chemotherapeutic drugs doxorubicin and camptothecin in these vesicles demonstrated a manyfold enhancement in the efficacies of the drugs both in vitro and across three advanced tumor models without any signs of toxicity. Both free and drug-loaded liposomes were maximally confined to the tumor site with low tissue concentration. These data indicate that PC-SA is a unique and promising liposome that, alone and as a combination therapy, has anticancer potential across a wide range of cancer types.

The use of an appropriate oleogelator in the structuring of vegetable oil is a crucial point of consideration. Sunflower wax (SFW) is used as an oleogelator and displays an excellent potential to bind vegetable oils. The current study aimed to look for the effects of hydrophobic (SPAN-80) and hydrophilic (TWEEN-80) emulsifiers on the oleogels prepared using SFW and sunflower oil (SO). The biodegradability and all formulations showed globular crystals on their surface that varied in size and number. Wax ester, being the most abundant component of SFW, was found to produce fibrous and needle-like entanglements capable of binding more than 99% of SO. The formulations containing 3 mg of liquid emulsifiers in 20 g of oleogels showed better mechanical properties such as spreadability and lower firmness than the other tested concentrations. Although the FTIR spectra of all the formulations were similar, which indicated not much variation in the molecular interactions, XRD diffractograms confirmed the presence of β′ form of fat crystals. Further, the mentioned formulations also showed larger average crystallite sizes, which was supported by slow gelation kinetics. A characteristic melting point (Tm~60 °C) of triglyceride was visualized through DSC thermograms. However, a higher melting point in the case of few formulations suggests the possibility of even a stable β polymorph. The formed oleogels indicated the significant contribution of diffusion for curcumin release. Altogether, the use of SFW and SO oleogels with modified properties using biodegradable emulsifiers can be beneficial in replacing saturated fats and fat-derived products.

In this work, oleogels of cocoa butter (CB), rice bran oil (RBO), and graphene oxide (GO) were prepared. The prepared oleogels were subjected to various characterization techniques such as bright-field microscopy, X-ray diffraction (XRD), crystallization kinetics, differential scanning calorimetry (DSC), and mechanical studies. The influence of increasing GO content on the in vitro drug release and ex vivo corneal permeation of the model drug (ciprofloxacin HCl—CPH) from the oleogels was also investigated. Bright-field micrographs showed that increment in GO content reduced the size of the globular particles of CB. XRD analysis revealed that CB was crystallized in its β’ and β polymorphic forms in the oleogels, which was in agreement with thermal studies. The mechanical characterization demonstrated that the presence of GO improved the elastic nature and stress-bearing properties of the oleogels. Moreover, GO altered the crystallization kinetics of CB in the oleogels in a composition-dependent manner. The in vitro release of CPH from the oleogels occurred through either Fickian diffusion or fat network relaxation or a combination thereof. Furthermore, the inclusion of GO enhanced the ex vivo permeation of CPH molecules across the caprine cornea. Hence, we concluded that the prepared oleogels could be explored as potential delivery systems for ophthalmic applications.

A 65-year-old hypertensive male, with co-existing benign prostatic hyperplasia for last 5 years was on tab telmisartan 40 mg and tab tamsulosin 0.4 mg, both once daily. He was found dyslipidemic on a routine investigation and was put on tab atorvastatin 10 mg once daily. The patient developed a petechial rash and bleeding from gums within a week of starting atorvastatin, and his platelet count dropped to 15,000/cmm. Atorvastatin was suspected to be the offender as no other causes of thrombocytopenia could be implicated. Atorvastatin was discontinued and intravenous steroid and platelet transfusion given. Platelet count improved gradually and became normal after 10 days. Causality assessment as per the Naranjo algorithm revealed a "probable association" with atorvastatin therapy.

Introduction: Fluoxetine is a commonly prescribed drug which is used in the psychiatric practice and adenomyosis is a common medical problem in women of the reproductive age group. Objective: To explore the role of fluoxetine in the causation of adenomyosis. Methods: Female Wistar rats (n=18) were divided into three groups (group I (the control), group II and group III) and they were treated with normal saline and oral fluoxetine (4mg/kg and 8 mg/kg) respectively for 100 days. Periodic serum prolactin measurements and histopathological examinations of the uterine horns of all the rats were done at the end. Comparison of the mean serum prolactin levels between the patients (n=15) who were diagnosed with adenomyosis, the healthy age sex matched controls and the female patients (n=20) who received fluoxetine for more than 3 months, before and after the fluoxetine administration, was done separately. Appropriate (paired or unpaired) t tests were used for the data analysis. Results: Out of the 12 test group rats, 10 rats showed the features of adenomyosis histopathologically, along with significantly (p < 0.05) raised serum prolactin levels. The mean serum prolactin levels of the patients of adenomyosis in comparison to those of the controls and of the patients who were treated with fluoxetine (before and after the fluoxetine administration), were significantly high (p=0.001 in both the cases). Conclusion: Fluoxetine may have some role in the causation of adenomyosis; although for a stronger evidence, the followup of the patients who are treated with fluoxetine on a long term basis should be ideal.

To improve the understanding and perception about rational prescribing among the Undergraduate (UG) students, a record based study 'exercise on prescription audit' was undertaken as self-directed learning strategy. Study was conducted on Objectively Structured Evaluation of pharmacotherapy taking one year record of prescriptions in Bed Head Tickets (BHTs) of discharged Ophthalmic in-patients. Standard format for prescription writing, WHO guide to Good prescribing and Essential Medicines were followed to assess the in-patient prescriptions. Students improved markedly (p< 0.001) in audit of real prescriptions. Results revealed that 37 types of drugs were prescribed over 948 BHTs. Completeness of the prescription showed 100% perfection in maximum indicators with exception in judicious investigations (99.89%), medication information (89.32%) and relevant advices for patient (97.12%). Subsidiary or symptomatic drugs (56.76%) were prescribed more than the core drugs (43.24% of total drugs prescribed). Generic prescription was 54.05%. Study in turn improved the understanding and perception about rational prescribing among the students. The students gained knowledge about the utilization of different types of dosage forms of drugs. Prescription audit as self-directed learning must be a tool for practical lesson of Pharmacology for UG-course as well as for PG-curriculum.

Bullous pemphigoid is an autoimmune cutaneous blistering disorder, the exact pathogenesis of which is still not fully elucidated. Drug-induced bullous pemphigoid eruptions are rare but have been reported earlier with the use of frusemide, psoralens, ibuprofen, galantamine hydrobromide, ACE inhibitors like captopril, spironolactone, penicillin, ampicillin, levofloxacin, penicillamine. We hereby report a case of metronidazole induced bullous pemphigoid (BP) in a 52-year-old male patient suffering from liver abscess following 4 days of drug administration. The skin biopsy findings obtained from the patient were consistent with the diagnosis of bullous pemphigoid (BP). Metronidazole was discontinued and symptomatic treatment was offered to the patient. Following withdrawal of metronidazole, the bullae subsided in the next 7-10 days without any significant residual scarring. The causality assessment performed as per the Naranjo algorithm revealed the case to be probable (Naranjo score 7).

Antibiotic induced skin rash in setting of infectious mononucleosis is often encountered in clinical practice. However, macrolides like azithromycin are considered relatively safe and till date only two cases of azithromycin induced rash in setting of infectious mononucleosis have been reported. The following report illustrates the case of a 23-year-old man suffering from infectious mononucleosis who exhibited a generalized cutaneous rash following treatment with azithromycin. Using the Naranjo ADR probability scale, this case of acute onset rash following azithromycin administration was found to be in ‘probable’ category. The mechanism of antibiotic-induced rash in patients suffering from infectious mononucleosis is incompletely understood. It has been suggested that the rash could result from virus mediated immunomodulation or due to altered drug metabolism. The report calls for cautious use of antibiotics in the setting of suspected viral infections like infectious mononucleosis as injudicious use might increase the risk of deleterious skin reactions and increase the cost of healthcare.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions (SCAR) which are frequently caused by exposure to drugs and cause significant morbidity and mortality. A careful literature search revealed that only a few reports of diclofenac induced and one case of serratiopeptidase associated case report of SJS or TEN have been published till date. However, to our knowledge, no case report of diclofenac-serratiopeptidase combination induced SJS have been published till date. In this backdrop, we describe the first case of a 62-year-old woman who developed diffuse, erythematous rash on face, trunk and both extremities which later turned into blisters following five day treatment with diclofenac and serratiopeptidase combination. There was extensive ulceration of buccal, genital and ocular mucosa. The body surface area involvement of the patient at the time of presentation was 9%. A provisional diagnosis of SJS was made by the treating physician. After administration of intravenous antibiotic, topical antiseptic, anti-histamine, topical lubricants, fluid therapy and parenteral nutrition patient recovered and were discharged.

Arsenic, an environmental toxin, significantly contributes to the development of several health problems. Epidemiological studies done across the globe have reported that a prolonged arsenic exposure has been associated with characteristic skin lesions, neuropathy and an increased risk of skin, lung, liver (angiosarcoma), bladder, kidney and colon cancers. In present study, we are reporting a case of a 60- year-old male, who presented with a large (5cm x 4cm) painless ulcer in fronto-parietal area of scalp, with occasional oozing of blood. X-ray of skull (AP and lateral view) revealed granular well-outlined osteolytic lesions in right fronto-parietal skull vault, which raised a suspicion of malignancy. An incisional biopsy was taken and histopathology revealed no evidence of malignancy. A benign, non-healing skin ulcer is rarely seen in a setting of chronic arsenicosis. His skin examination showed characteristic fine freckles of spotted pigmentary changes i.e. classic rain-drop pigmentations which were present all over the body, particularly on trunk, palms and soles. Arsenic levels seen in hair and nail of the patient were 1.23 micrograms/gram and 3.26 micrograms/gram respectively, which were in accordance with WHO suggested diagnostic criteria of chronic arsenicosis.

Influenza A virus (IAV) represents a worldwide threat to public health by causing severe morbidity and mortality every year. Due to high mutation rate, new strains of IAV emerge frequently. These IAVs are often drug-resistant and require vaccine reformulation. A promising approach to circumvent this problem is to target host cell determinants crucial for IAV infection, but dispensable for the cell. Several RNAi-based screens have identified about one thousand cellular factors that promote IAV infection. However, systematic analyses to determine their specific functions are lacking. To address this issue, we developed quantitative, imaging-based assays to dissect seven consecutive steps in the early phases of IAV infection in tissue culture cells. The entry steps for which we developed the assays were: virus binding to the cell membrane, endocytosis, exposure to low pH in endocytic vacuoles, acid-activated fusion of viral envelope with the vacuolar membrane, nucleocapsid uncoating in the cytosol, nuclear import of viral ribonucleoproteins, and expression of the viral nucleoprotein. We adapted the assays to automated microscopy and optimized them for high-content screening. To quantify the image data, we performed both single and multi-parametric analyses, in combination with machine learning. By time-course experiments, we determined the optimal time points for each assay. Our quality control experiments showed that the assays were sufficiently robust for high-content analysis. The methods we describe in this study provide a powerful high-throughput platform to understand the host cell processes, which can eventually lead to the discovery of novel anti-pathogen strategies.

Influenza A virus (IAV) enters host cells by endocytosis followed by acid-activated penetration from late endosomes (LEs). Using siRNA silencing, we found that histone deacetylase 8 (HDAC8), a cytoplasmic enzyme, efficiently promoted productive entry of IAV into tissue culture cells, whereas HDAC1 suppressed it. HDAC8 enhanced endocytosis, acidification, and penetration of the incoming virus. In contrast, HDAC1 inhibited acidification and penetration. The effects were connected with dramatic alterations in the organization of the microtubule system, and, as a consequence, a change in the behavior of LEs and lysosomes (LYs). Depletion of HDAC8 caused loss of centrosome-associated microtubules and loss of directed centripetal movement of LEs, dispersing LE/LYs to the cell periphery. For HDAC1, the picture was the opposite. To explain these changes, centrosome cohesion emerged as the critical factor. Depletion of HDAC8 caused centrosome splitting, which could also be induced by depleting a centriole-linker protein, rootletin. In both cases, IAV infection was inhibited. HDAC1 depletion reduced the splitting of centrosomes, and enhanced infection. The longer the distance between centrosomes, the lower the level of infection. HDAC8 depletion was also found to inhibit infection of Uukuniemi virus (a bunyavirus) suggesting common requirements among late penetrating enveloped viruses. The results established class I HDACs as powerful regulators of microtubule organization, centrosome function, endosome maturation, and infection by IAV and other late penetrating viruses.

Freeze drying is one of the popular methods of fabrication for poly(lactide-co-glycolide) (PLGA) microspheres incorporated polymer scaffolds. However, the consequence of microspheres incorporation on physical and biological properties of scaffold has not been studied yet. In this study, attempt has been made to characterize the effect of PLGA microsphere incorporation on the physical properties of freeze-dried gelatin scaffold and its influence on cytocompatibility. Scaffolds loaded with varying amount of PLGA microspheres (10%, 1%, 0.1% w/w) were subjected to microarchitecture analysis, swelling, porosity, mechanical properties, biodegradation, cell adhesion, and cell proliferation studies. Results revealed that an increase in percentage loading of microspheres reduced the pore size and uniformity of the pore structure. Moreover, loading of PLGA microspheres up to 1% w/w significantly increased porosity, swelling, and mechanical properties of the scaffold but variations were not proportional for 10% w/w loading. Results also showed that PLGA microspheres have no significant effect on cell adhesion but influenced the growth kinetics.

A novel bioanalogue hydroxyapatite (HAp)/chitosan phosphate (CSP) nanocomposite has been synthesized by a solution-based chemical methodology with varying HAp contents from 10 to 60% (w/w). The interfacial bonding interaction between HAp and CSP has been investigated through Fourier transform infrared absorption spectra (FTIR) and x-ray diffraction (XRD). The surface morphology of the composite and the homogeneous dispersion of nanoparticles in the polymer matrix have been investigated through scanning electron microscopy (SEM) and transmission electron microscopy (TEM), respectively. The mechanical properties of the composite are found to be improved significantly with increase in nanoparticle contents. Cytotoxicity test using murine L929 fibroblast confirms that the nanocomposite is cytocompatible. Primary murine osteoblast cell culture study proves that the nanocomposite is osteocompatible and highly in vitro osteogenic. The use of CSP promotes the homogeneous distribution of particles in the polymer matrix through its pendant phosphate groups along with particle-polymer interfacial interactions. The prepared HAp/CSP nanocomposite with uniform microstructure may be used in bone tissue engineering applications.