Intermittent fasting along with hydroalcoholic extract of Centella-asiatica ameliorates sub-acute hypoxia-induced ischemic stroke in adult zebrafish.

Reduced blood flow (hypoxia) to the brain is thought to be the main cause of strokes because it deprives the brain of oxygen and nutrients. An increasing amount of evidence indicates that the Centella-Asiatica (HA-CA) hydroalcoholic extract has a variety of pharmacological benefits, such as antioxidant activity, neuroprotection, anti-inflammatory qualities, and angiogenesis promotion. Intermittent fasting (IF) has neurological benefits such as anti-inflammatory properties, neuroprotective effects, and the ability to enhance neuroplasticity. The current study evaluates the combined effect of IF (for 1, 6, and 12 days) along with HA-CA (daily up to 12 days) in adult zebrafish subjected to hypoxia every 5 min for 12 days followed by behavioral (novel tank and open-field tank test), biochemical (SOD, GSH-Px, and LPO), inflammatory (IL-10, IL-1ß, and TNF-α), mitochondrial enzyme activities (Complex-I, II, and IV), signaling molecules (AMPK, MAPK, GSK-3ß, Nrf2), and imaging/staining (H&E, TTC, and TEM) analysis. Results show that sub-acute hypoxia promotes the behavioral alterations, and production of radical species and alters the oxidative stress status in brain tissues of zebrafish, along with mitochondrial dysfunction, neuroinflammation, and alteration of signaling molecules. Nevertheless, HA-CA along with IF significantly ameliorates these defects in adult zebrafish as compared to their effects alone. Further, imaging analysis significantly provided evidence of infarct damage along with neuronal and mitochondrial damage which was significantly ameliorated by IF and HA-CA. The use of IF and HA-CA has been proven to enhance the physiological effects of hypoxia in all dimensions.

Assessment of the antigenic evolution of a clade 6B.1 human H1N1pdm influenza virus revealed differences between ferret and human convalescent sera.

BACKGROUND: Influenza viruses continually acquire mutations in the antigenic epitopes of their major viral antigen, the surface glycoprotein haemagglutinin (HA), allowing evasion from immunity in humans induced upon prior influenza virus infections or vaccinations. Consequently, the influenza strains used for vaccine production must be updated frequently. METHODS: To better understand the antigenic evolution of influenza viruses, we introduced random mutations into the HA head region (where the immunodominant epitopes are located) of a pandemic H1N1 (H1N1pdm) virus from 2015 and incubated it with various human sera collected in 2015-2016. Mutants not neutralized by the human sera were sequenced and further characterized for their haemagglutination inhibition (HI) titers with human sera and with ferret sera raised to H1N1pdm viruses from 2009 to 2015. FINDINGS: The largest antigenic changes were conferred by mutations at HA amino acid position 187; interestingly, these antigenic changes were recognized by human, but not by ferret serum. H1N1pdm viruses with amino acid changes at position 187 were very rare until the end of 2018, but have become more frequent since; in fact, the D187A amino acid change is one of the defining changes of clade 6B.1A.5a.1 viruses, which emerged in 2019. INTERPRETATION: Our findings indicate that amino acid substitutions in H1N1pdm epitopes may be recognized by human sera, but not by homologous ferret sera. FUNDING: This project was supported by funding from the NIAID-funded Center for Research on Influenza Pathogenesis (CRIP, HHSN272201400008C).

Myomodulation with Facial Fillers: A Comprehensive Technical Guide and Retrospective Case Series.

The article titled "Myomodulation with Facial Fillers: A Comprehensive Technical Guide and Retrospective Case Series" by Coimbra et al. in Aesthetic Plastic Surgery presents a technical guide for holistic facial treatment using hyaluronic acid (HA) fillers and a map for addressing individual facial units through myomodulation. The authors' approach is appreciated for its value. However, concerns arise about the employed methodologies. Understanding HA's properties is vital for treatment standardization. The significance of HA's rheological properties, encompassing viscosity, elasticity, and cohesiveness, is critical for optimal dermal filler selection. The authors' insights are acknowledged, yet further analysis considering these factors is recommended. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Ethanol-Extracted Acorn Induces Anti-Inflammatory Effects in Human Keratinocyte and Production of Hyaluronic Acid in Human Fibroblasts.

Acorn (Quercus acutissima CARR.) has been used in traditional food and medicinal ethnopharmacology in Asia, and it has shown multifarious functions such as antidementia, antiobesity, and antiasthma functions. However, there is limited scientific evidence about the efficacy of acorn for ameliorating skin problems. Treatment with ethanol-extracted acorns (EeA's) ablated the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX2), monocyte chemoattractant protein-1 (MCP-1), and interleukin (IL)-8 stimulated by tumor necrosis factor (TNF)-α in human adult low calcium high temperature (HaCaT) cells under sublethal dosages. In addition, treatment with EeA dose dependently inhibited the ex vivo hyper keratin formation induced by TNF-α in HaCaT cells in conjunction with the blockade of cytokeratin-1 (CK-1) and cytokeratin-5 (CK-5) expression. Moreover, EeA treatment stimulated the expression of hyaluronic acid (HA) expression in human fibroblasts in a dose-dependent manner. Linoleamide was identified as the functional component of EeA using preparative high-performance liquid chromatography and ultra high performance liquid chromatography-mass spectrometry-mass spectrometry analysis, and the anti-inflammatory features and enhanced HA expression were verified. Collectively, these results suggest the efficacy of EeA supplementation in improving skin problems via anti-inflammation and upregulating HA production.

Interpenetration Phenomena via Anion Template Effects in Fe(II) and Co(II) Coordination Networks with a Bis-(1,2,4-triazole) Ligand.

Seven new coordination networks, [Fe(tbbt)3](BF4)2 (1), [Co(tbbt)3](BF4)2 (2), [Fe(tbbt)3](ClO4)2 (3), [Co(tbbt)3](ClO4)2 (4), [Fe(NCS)2(tbbt)2] (5), [Co(NCS)2(tbbt)2] (6), and [Fe(H2O)2(tbbt)2]Br2·2H2O (7), were synthesized with the linker 1,1'-(trans-2-butene-1,4-diyl)bis-1,2,4-triazole (tbbt) and structurally investigated. The structure of complexes 1-4 is composed of three interpenetrating, symmetry-related 3D networks. Each individual 3D network forms a primitive, nearly cubic lattice (pcu) with BF4- or ClO4- anions present in the interstitial spaces. The structure of compounds 5 and 6 is composed of two-dimensional sql layers, which are parallel to each other in the AB stacking type. These layers are interpenetrated by one-dimensional chains, both having the same formula unit, [M(NCS)2(tbbt)2] (M = Fe, Co). The structure of compound 7 consists of parallel, two-dimensional sql layers in the ABCD stacking type. The interpenetration in 1-6 is not controlled by π-π-interactions between the triazole rings or C=C bonds, as could have been expected, but by (triazole)C-H⋯F4B, C-H⋯O4Cl, and C-H⋯SCN anion hydrogen bonds, which suggests a template effect of the respective non-coordinated or coordinated anion for the interpenetration. In 7, the (triazole)C-H⋯Br anion interactions are supplemented by O-H⋯O and O-H⋯Br hydrogen bonds involving the aqua ligand and crystal water molecules. It is evident that the coordinated and non-coordinated anions play an essential role in the formation of the networks and guide the interpenetration. All iron(II) coordination networks are colorless, off-white to yellow-orange, and have the metal ions in the high-spin state down to 77 K. Compound 5 stays in the high spin state even at temperatures down to 10 K.

Combined Bipolar Radiofrequency and Non-Crosslinked Hyaluronic Acid Mesotherapy Protocol to Improve Skin Appearance and Epidermal Barrier Function: A Pilot Study.

BACKGROUND: Age-associated changes in epidermal hydration, pigmentation, thickness and cell renewal influence skin appearance and can lead to laxity, dryness and poor skin tone. The aim of this pilot study was to assess the synergistic effects of a new bipolar radiofrequency plus non-crosslinked hyaluronic acid (HA) mesotherapy protocol compared with radiofrequency alone on skin appearance and markers of epidermal function. METHODS: This prospective, single-center, split-face pilot study recruited women aged 25-65 years with dryness and laxity of the facial skin defined by a trans-epidermal water loss (TEWL) value of ≥26 g/m2/h. Subjects were treated with a bipolar radiofrequency device on both sides of the face. This was immediately followed by needle hyaluronic acid (HA) treatment on one side of the face with 2.5 mL of a non-crosslinked HA. Photographic documentation, analysis of epidermal barrier function parameters, and high frequency (HF) ultrasound analysis were performed prior to treatment and at 28 days. RESULTS: Twenty female subjects with a mean age of 46 (range 29 to 54) years and dry and lax facial skin were included. TEWL was reduced and skin hydration improved to a greater extent with the combined radiofrequency plus mesotherapy protocol compared with radiofrequency alone (-5.8% vs. +3.9% and +23.1% vs. +1.0%, respectively). The combined protocol was also associated with greater improvements in melanin (-7.5% vs. -1.5%) and erythema values (-7.2% vs. +3.0%), respectively. Ultrasound measures of epidermal thickness and epidermal density were greater after the combined protocol compared with radiofrequency alone (12.0% vs. 5.6% and 57.7% vs. 7.1%, respectively). Both treatments were well-tolerated. CONCLUSIONS: The combined bipolar radiofrequency and HA mesotherapy protocol provided greater improvements in skin hydration, firmness and tone compared with radiofrequency alone. The combination treatment was also associated with greater epidermal thickness and density and increased keratinocyte differentiation suggesting a synergistic effect of both treatments on epidermal homeostasis and barrier function. Both treatments were well-tolerated and led to improvements in facial appearance.

[Effects of catgut embedding and PGLA embedding at "Zusanli" (ST 36) on skin mast cells, substance P and histamine in healthy rats].

OBJECTIVE: To observe the effects of catgut embedding and polyglycolic acid/poly-lactic acid (PGLA) embedding at "Zusanli" (ST 36) on the activation of local skin mast cells (MC), and expression of substance P (SP) and histamine (HA), and to explore the mechanism of the temporal stimulation effect of acupoint catgut embedding and provide a foundation for further research on the initiation mechanism of acupoint catgut embedding. METHODS: One hundred and sixty male SPF-grade SD rats were randomly divided into a blank group (10 rats), a sham-embedding group (50 rats), a catgut group (50 rats), and a PGLA group (50 rats). Each intervention group was further randomly divided into five subgroups according to the time points after intervention: 8 hours, 3 days, 7 days, 14 days, and 21 days, with 10 rats in each subgroup. One-time sham-embedding, catgut embedding and PGLA embedding was given at left "Zusanli" (ST 36) in each intervention group, respectively. The skin and subcutaneous connective tissue of the left "Zusanli" (ST 36) were collected at the corresponding time points after intervention, except for the blank group (only one day before intervention). Toluidine blue staining was used to detect MC count and degranulation, and immunohistochemical staining was used to detect the expression of SP and HA positive cells. RESULTS: There was no significant difference in MC count between the subgroups of each intervention group and the blank group (P>0.05). There was no significant difference in MC count between the subgroups of the catgut group and the PGLA group (P>0.05). The MC count in the 8-hour subgroup of PGLA group was higher than that in the 8-hour subgroup of catgut group (P<0.05), while the MC count in the 21-day subgroup of PGLA group was lower than that in the 21-day subgroup of catgut group (P<0.05). Compared with the blank group, the degranulation rates of MC were increased in the 8-hour and 3-day subgroups of sham-embedding group, 8-hour, 3-day, and 7-day subgroups of catgut group, and 8-hour, 3-day, 7-day, and 14-day subgroups of PGLA group (P<0.01, P<0.05, P<0.001). There was no significant difference in the degranulation rate of MC between the subgroups of the catgut group and the PGLA group (P>0.05), and no significant difference in the degranulation rate of MC between the two embedding groups at the same time point (P>0.05). Compared with the blank group, the expression of SP positive cells was increased in the 8-hour subgroup of sham-embedding group, 8-hour, 3-day, 7-day, and 14-day subgroups of catgut group, and 3-day, 7-day, and 14-day subgroups of PGLA group (P<0.001, P<0.05). The expression of SP positive cells in the 7-day subgroup of catgut group was higher than that in the 8-hour subgroup of catgut group (P<0.05), while the expression of SP positive cells in the 14-day subgroup of catgut group was lower than that in the 7-day subgroup of catgut group (P<0.001). The expression of SP positive cells in the 7-day subgroup of PGLA group was higher than that in the 3-day subgroup of PGLA group (P<0.05), while the expression of SP positive cells in the 14-day subgroup of PGLA group was lower than that in the 7-day subgroup of PGLA group (P<0.01). There was no significant difference in the expression of SP positive cells between the subgroups of the two embedding groups at the same time point (P>0.05). Compared with the blank group, the expression of HA positive cells was increased in the 8-hour, 3-day subgroups of sham-embedding group, 8-hour, 3-day, 7-day, and 14-day subgroups of catgut group, and 8-hour, 3-day, 7-day, 14-day, and 21-day subgroups of PGLA group (P<0.001, P<0.01, P<0.05). The expression of HA positive cells in the 14-day subgroup of catgut group was lower than that in the 7-day subgroup of catgut group (P<0.05), while the expression of HA positive cells in the 3-day subgroup of PGLA group was higher than that in the 8-hour subgroup of PGLA group (P<0.05), and the expression of HA positive cells in the 14-day subgroup of PGLA group was lower than that in the 7-day subgroup of PGLA group (P<0.05). The expression of HA positive cells in the 3-day subgroup of PGLA group was higher than that in the 3-day subgroup of catgut group (P<0.05). CONCLUSION: Catgut and PGLA embedding at "Zusanli" (ST 36) in healthy rats could induce changes in local skin MC, SP, and HA, which may be one of the mechanisms of the temporal stimulation effect after acupoint embedding. There are certain differences between different suture materials. A moderate inflammatory response in the acupoint area, mediated by MC and involving SP and HA, may be one of the initiating factors for the effect of acupoint catgut embedding.

The Extent of the Use of Multivitamins and Multimineral Supplements Without Clinically Measurable Benefits Among Adults in Ha'il, Saudi Arabia: A Cross-Sectional Study.

Introduction Multivitamins and multiminerals (MVMM) are nutritional supplements that contain a wide range of important nutrients. The use of vitamins and minerals has been showing a tremendous increase over the past few years due to the high demand for supplements to replenish nutritional deficiencies. Purpose This study aimed to assess MVMM usage, the reasons why people chose to use MVMM, and the factors related to this usage. Methodology A cross-sectional study was conducted on adults living in Ha'il, Saudi Arabia. Data were collected between October 31 and December 14, 2022, a self-administered online questionnaire was used, and data were analyzed using SPSS version 25.0 (IBM Corp, Armonk, NY). Results A total of 310 participants enrolled in the study, of which 240 (77.42%) were females and 70 (22.58%) were males. The extent of the use of MVMM supplements without clinically measurable benefits was more than half of the present study participants (58.71%). There was a significant difference between MVMM use and gender or employment status. MVMM usage on a regular basis was found to be associated with satisfaction with the outcomes. The majority of participants used MVMM to promote health. Calcium and vitamin D were found to be the most common types of dietary supplements used. Conclusion The use of MVMM supplements without clinically measurable benefits was more prevalent among females. It is important to promote public health awareness programs about the benefits and risks of overdose.

Preventing Persistence of HPV Infection with Natural Molecules.

Human papillomavirus (HPV) infection is one the most common sexually transmitted infections worldwide. In most cases, the infection is temporary and asymptomatic; however, when persistent, it may lead to lesions that can evolve into cancer in both women and men. Nowadays, prophylactic vaccination is the primary preventive strategy for HPV infections, but vaccines do not cover all types of HPV strains. Scientific research has uncovered the beneficial role of some natural supplements in preventing persistent HPV infections or treating HPV-related lesions. We review the current insight into the roles of natural molecules in HPV infection with a special focus on epigallocatechin gallate (EGCG), folic acid, vitamin B12, and hyaluronic acid (HA). Specifically, EGCG from green tea extracts plays a critical role in suppressing HPV oncogenes and oncoproteins (E6/E7), which are responsible for HPV oncogenic activity and cancer development. Folic acid and vitamin B12 are essential vitamins for multiple functions in the body, and accumulating evidence suggests their importance in maintaining a high degree of methylation of the HPV genome, thus decreasing the likelihood of causing malignant lesions. HA, due to its re-epithelizing property, may prevent HPV virus entry in damaged mucosa and epithelia. Thereby, based on these premises, the combination of EGCG, folic acid, vitamin B12, and HA may be a very promising therapeutic approach to prevent HPV persistence.

Serum 25-hydroxyvitamin D and hyaluronic acid levels as markers of fibrosis in patients with chronic liver disease at the main tertiary referral hospital in Ghana: A case-control study design.

Background and Aims: Liver fibrosis leading to chronic liver disease (CLD) is a major cause of morbidity, mortality and health-care expenditure worldwide. The "gold standard" for diagnosis and staging of liver fibrosis is histological analysis of liver tissue obtained by liver biopsy, an invasive procedure. Therefore, there is the need to identify noninvasive and inexpensive markers for diagnosis and staging of liver fibrosis. This study aimed at evaluating the correlation of hyaluronic acid (HA) and 25-hydroxyvitamin D (25-OH vitamin D) serum levels as markers of fibrosis with histologically staged and graded liver biopsies obtained from CLD patients. Methods: This was a case-control study involving 40 CLD patients requiring liver biopsies and 40 controls. Liver biopsies were staged to determine the degree of fibrosis. Serum levels of 25-OH vitamin D and HA were determined using ELISA. Statistical analyses were performed to determine differences in HA and 25-OH vitamin D levels between controls and patients as well as to correlate the biomarkers with the stages of fibrosis. Results: CLD patients showed significant (p < 0.001) increase in the levels of AST, ALT, GGT, compared to the controls. Patients also had significantly (p < 0.001) lower serum 25-OH vitamin D and higher HA (p < 0.001) levels compared to the controls. Additionally, 25-OH vitamin D levels of the CLD patients were significantly different across the stages of liver fibrosis likewise serum HA levels. Furthermore, 25-OH vitamin D levels inversely correlated with the severity of liver fibrosis. A significant negative correlation (r = -0.33, p < 0.05) between CLD patients' HA and 25-OH vitamin D were found. Conclusion: CLD patients had significantly reduced serum 25-OH vitamin D and higher HA. Both markers correlated with the degree of liver fibrosis. These findings have major clinical translatable implication in the use of vitamin D supplementation in the management of CLD in Ghana.

HA PEGylated Filler in Association with an Infrared Energy Device for the Treatment of Facial Skin Aging: 150 Day Follow-Up Data Report.

BACKGROUND: The face is the area most exposed to the normal course of skin aging, both intrinsically and extrinsically. The aim of the study was to evaluate the cellular and clinical response of a therapeutic protocol aimed at countering facial skin aging. MATERIALS AND METHODS: Twenty female patients with facial skin laxity and photodamage underwent combined therapy including mesotherapy using non-cross-linked hyaluronic acid with calcium hydroxyapatite and an infrared energy-based device treatment with subsequent implementation of PEG-cross-linked hyaluronic acid soft tissue fillers. To evaluate the benefits, patients underwent histological, immunological, and biomechanical evaluations before the treatment and at 21 and 150 days after the treatment. RESULTS: The histological results at 21 days and 150 days after the procedure showed an increase in the number of fibroblasts and angiogenesis. As for the immunological aspect, it was shown that the treatment has an immunomodulating action, avoiding the activation of CD4 and CD8 cells. Biomechanical data showed that, at 150 days after treatment, the average changes in skin elasticity increased by 72% and the skin hydration increased by 49%. CONCLUSIONS: A combination of an infrared energy-based device treatment with both non-cross-linked hyaluronic acid and novel PEG-cross-linked hyaluronic acid leads to numerous positive cutaneous changes after histological, immunological, and biomechanical evaluations.

A New Stilbene Glucoside from Biotransformation-Guided Purification of Chinese Herb Ha-Soo-Oh.

Ha-Soo-Oh is a traditional Chinese medicine prepared from the roots of Polygonum multiflorum Thunb. The herb extract has been widely used in Asian countries as a tonic agent and nutritional supplement for centuries. To identify new bioactive compounds in Chinese herbs, the biotransformation-guided purification (BGP) process was applied to Ha-Soo-Oh with Bacillus megaterium tyrosinase (BmTYR) as a biocatalyst. The result showed that a major biotransformed compound could be purified using the BGP process with preparative high-performance liquid chromatography (HPLC), and it was confirmed as a new compound, 2,3,5,3',4'-pentahydroxystilbene-2-O-ß-glucoside (PSG) following mass and nucleic magnetic resonance (NMR) spectral analyses. PSG was further confirmed as a biotransformation product from 2,3,5,4'-tetrahydroxystilbene-2-O-ß-glucoside (TSG) by BmTYR. The new PSG exhibited 4.7-fold higher 1,1-diphenyl-2-picrylhydrazine (DPPH) free radical scavenging activity than that of TSG. The present study highlights the potential usage of BGP in herbs to discover new bioactive compounds in the future.

Collagenase-I decorated co-delivery micelles potentiate extracellular matrix degradation and hepatic stellate cell targeting for liver fibrosis therapy.

Liver fibrosis is a pathological process of multiple chronic liver diseases progressing to cirrhosis for which there are currently no effective treatment options. During fibrosis progression, the overproduction of extracellular matrix (ECM) collagen secreted by hepatic stellate cells (HSCs) greatly impedes drug delivery and reduces drug therapeutic effects. In this study, a glycyrrhetinic acid (GA)-conjugated prodrug micellar system with collagenase I (COL) decoration (COL-HA-GA, abbreviated as CHG) was designed to codelivery sorafenib (Sora/CHG, abbreviated as S/CHG) for potentiating ECM degradation and HSCs targeting on liver fibrosis therapy. In ECM barrier models established in vitro or in vivo, CHG micelles efficiently degraded pericellular collagen and demonstrated enormous ECM penetration abilities as well as superior HSCs internalization. Moreover, CHG micelles exhibited more Sora & GA accumulations and activated HSCs targeting efficiencies in the fibrotic livers than those in the normal livers. More importantly, S/CHG micelles were more effective in anti-liver fibrosis by lowering the collagen content, inhibiting the HSCs activation, as well as down-regulating the fibrosis-related factors, leading to reverse the fibrotic liver to normal liver through the multi-mechanisms including angiogenesis reduction, liver fibrosis microenvironment regulation, and epithelial-mesenchymal transition inhibition. In conclusion, the developed COL decorated nano-codelivery system with fibrotic ECM collagen degradation and activated HSCs targeting dual-functions exhibited great potential for liver fibrosis therapy. STATEMENT OF SIGNIFICANCE: A glycyrrhetinic acid (GA)-conjugated prodrug with collagenase I (COL) decoration (CHG) was designed for codelivery with sorafenib (S/CHG), potentiating extracellular matrix (ECM) degradation-penetration and hepatic stellate cells (HSCs) targeting on liver fibrosis therapy. In ECM barrier models, CHG micelles efficiently degraded pericellular collagen and demonstrated ECM penetration abilities, as well as displayed superior HSCs internalization. Moreover, S/CHG micelles were more effective in anti-liver fibrosis by lowering the collagen content, inhibiting the HSCs activation, as well as down-regulating cytokines, reversing the fibrotic liver to normal through various mechanisms. In conclusion, the developed fibrotic ECM degradation and HSCs targeting dual-functional nano-codelivery system provided a prospective potentiality in liver fibrosis therapy.

A behavioural study of hydrothermally derived novel alumina/magnesia/hydroxyapatite (Al2O3/MgO/HA) bioceramic nanocomposite.

Regeneration and regrowth of human bones is a gradual and time-consuming process. Therefore scaffolds are required to hold the bones in position and give them time to heal well. Though hydroxyapatite (HA) is a potential candidate, its weak mechanical nature has made it undesirable. To overcome this hurdle, a novel nanocomposite of HA with alumina (Al2O3) and magnesia (MgO) was prepared by hydrothermal method in this study. The constitution, composition and conformation of the Al2O3/MgO/HA nanocomposite were affirmed via X-ray Diffraction (XRD), Fourier-Transform Infra-Red (FTIR) and imaging tests. Vicker's hardness test evinces the mechanical calibre of the nanocomposite. A perspective load-displacement analysis was done by means of Onitsch and Kick's power laws. The nanocomposite excelled above par with a hardness of 5.19 GPa and fracture toughness of 1.27 MPam1/2. This holistic progress makes this nanocomposite a very desirable bone implant material.

Immunogenicity and cross-protective efficacy of recombinant H5HA1 protein of clade 2.3.2.1a highly pathogenic H5N1 avian influenza virus expressed in E.coli.

The global spread of H5N1 highly pathogenic avian influenza virus (HPAIV) in poultry has caused great economic loss to the poultry farmers and industry with significant pandemic threat. The current study involved production of recombinant HA1 protein of clade 2.3.2.1a H5N1 HPAIV (rH5HA1) in E.coli and evaluation of its protective efficacy in chickens. Purification under denaturing conditions and refolding by dialysis against buffers containing decreasing concentrations of urea was found to preserve the biological activity of the expressed recombinant protein as assessed by hemagglutination assay, Western blot and ELISA. The Montanide ISA 71 VGA adjuvanted rH5HA1 protein was used for immunization of chickens. Humoral response was maintained at a minimum of 4log2 hemagglutination inhibition (HI) titre till 154 days post 2nd booster. We evaluated the protective efficacy of rH5HA1 protein in immunized chickens by challenging them with homologous (2.3.2.1a) and heterologous (2.3.2.1c) clades of H5N1 HPAIV. In both the groups, the HI titre significantly increased (P < 0.05) after challenge and the virus shedding significantly (P < 0.05) reduced between 3rd and 14th day post challenge. The virus shedding ratio in oro-pharyngeal swabs did not differ significantly between both the groups except on 7 days post challenge and during the entire experimental period in cloacal swabs. These results indicate that rH5HA1 was able to induce homologous and cross protective immune response in chickens and could be a potential vaccine candidate used for combating the global spread of H5N1 HPAIV threat. To our knowledge, this is the first study to report immunogenicity and protective efficacy of prokaryotic recombinant H5HA1 protein in chicken.

Advanced application of stimuli-responsive drug delivery system for inflammatory arthritis treatment.

Inflammatory arthritis is a major cause of disability in the elderly. This condition causes joint pain, loss of function, and deterioration of quality of life, mainly due to osteoarthritis (OA) and rheumatoid arthritis (RA). Currently, available treatment options for inflammatory arthritis include anti-inflammatory medications administered via oral, topical, or intra-articular routes, surgery, and physical rehabilitation. Novel alternative approaches to managing inflammatory arthritis, so far, remain the grand challenge owing to catastrophic financial burden and insignificant therapeutic benefit. In the view of non-targeted systemic cytotoxicity and limited bioavailability of drug therapies, a major concern is to establish stimuli-responsive drug delivery systems using nanomaterials with on-off switching potential for biomedical applications. This review summarizes the advanced applications of triggerable nanomaterials dependent on various internal stimuli (including reduction-oxidation (redox), pH, and enzymes) and external stimuli (including temperature, ultrasound (US), magnetic, photo, voltage, and mechanical friction). The review also explores the progress and challenges with the use of stimuli-responsive nanomaterials to manage inflammatory arthritis based on pathological changes, including cartilage degeneration, synovitis, and subchondral bone destruction. Exposure to appropriate stimuli induced by such histopathological alterations can trigger the release of therapeutic medications, imperative in the joint-targeted treatment of inflammatory arthritis.

The inhibition effects and mechanisms of sulfated chitooligosaccharides on influenza A virus in vitro and in vivo.

Sulfated chitooligosaccharide was reported to possess inhibition effect on human immunodeficiency virus (HIV) entry into host cells. Herein, we prepared chitooligosaccharide COS and its sulfate derivative SCOS and explored whether the sulfation modification can enhance the anti-influenza A virus (IAV) activity of COS. Interestingly, we discovered that SCOS possessed broad-spectrum anti-IAV effects with low toxicity, while the non-sulfated chitooligosaccharide COS had very low inhibition on IAV, verifying that the sulfation modification is essential for the anti-IAV actions of chitooligosaccharide. SCOS may target virus hemagglutinin (HA) protein to block both virus adsorption and membrane fusion processes. Oral administration of SCOS significantly decreased pulmonary viral titers and improved survival rate in IAV infected mice, comparable to the effects of Oseltamivir. Therefore, our findings support further studies on the use of SCOS as a novel entry inhibitor for IAV and as a supplement to current therapeutics for influenza.

Quercetin and polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a reproductive endocrine disease, and results to opsomenorrhea or amenorrhea, hairy, acne, acanthosis, infertility, abortion. In the long term, PCOS may also increase the risk of endometrial cancer, diabetes, hypertension, dyslipidemia and other diseases. Till now there is no specific drug for PCOS due to the unclearness of the cause and pathogenesis, as current treatments for PCOS only target certain symptoms. Quercetin (QUR) is a flavonoid drug widely found in Chinese herbal medicines, fruits, leaves, vegetables, seeds and plants roots. Studies on other diseases have found that QUR has anti-oxidant, anti-inflammatory, anti-insulin resistance, anti-cancer and other effects. Some studies have shown that serum testosterone (T), luteinizing hormone (LH), the LH/follicule-stimulating hormone (FSH) ratio, fasting glucose, fasting insulin, HOMA-IR and lipid levels are reduced in PCOS patients with QUR treatment. However, the mechanisms of QUR in PCOS patients have not been completely elucidated. In this review, we retrospect the basic characteristics of QUR, and in vitro studies, animal experiments and clinical trials of QUR and plant extracts containing QUR in the treatment of PCOS. We also summarized the effects and mechanism of QUR in ovarian cells in vitro and PCOS model rats, the changes in relevant parameters after QUR administration in PCOS patients, and its potentially therapeutic applications.

Modulation of Gut Barrier Functions in Ulcerative Colitis by Hyaluronic Acid System.

The active stages of intestinal inflammation and the pathogenesis of ulcerative colitis are associated with superficial mucosal damage and intermittent wounding that leads to epithelial barrier defects and increased permeability. The standard therapeutic interventions for colitis have focused mainly on maintaining the remission levels of the disease. Nonetheless, such treatment strategies (using anti-inflammatory, immunomodulatory agents) do not address colitis' root cause, especially the mucosal damage and dysregulated intestinal barrier functions. Restoration of barrier functionality by mucosal healing or physical barrier protecting strategies shall be considered as an initial event in the disease suppression and progression. Herein, a biphasic hyaluronan (HA) enema suspension, naïve-HA systems that protect the dysregulated gut epithelium by decreasing the inflammation, permeability, and helping in maintaining the epithelial barrier integrity in the dextran sodium sulfate-induced colitis mice model is reported. Furthermore, HA-based system modulates intestinal epithelial junctional proteins and regulatory signaling pathways, resulting in attenuation of inflammation and mucosal protection. The results suggest that HA-based system can be delivered as an enema to act as a barrier protecting system for managing distal colonic inflammatory diseases, including colitis.

Bio-diesel production of sunflower through sulphur management in a semi-arid subtropical environment.

Energy security is a prime focus of policy makers to support agriculture, industrialisation, and transportation. Due to limited conventional energy sources, there is a need to harness non-conventional energy sources. In this regard, one of the proposed approaches is using biomass (e.g. energy crops) to produce biofuel-a renewable source of energy. Sunflower has several agronomic features to be exploited for a renewable, non-conventional, and environment-friendly source of bioenergy. Sulphur (S) fertilisation holds key for realising sunflower potential for seed and oil yield. In response to variable S supply rates, here we compared and quantified sunflower yield (seed, oil, and biodiesel) and biodiesel quality according to the ASTM international standards. We used a combined approach of field experimentation and rigorous lab analysis. Firstly, in a field experiment laid out in randomised complete block design with split-plot arrangement, response of two local sunflower hybrids (FH-331 and FH-689) to four S supply rates (0, 25, 50, 75 kg S ha-1) was evaluated in terms of agronomic traits. Experimental data showed that fertilisation of S significantly influenced growth and yield (seed, oil) traits; the response was different between two hybrids which also interacted with S supply rate. FH-331 recorded the highest achene yield at S fertilisation of 75 kg S ha-1, whereas FH-689 recorded the highest achene yield at 50 kg ha-1; achene yield of FH-331 was 13.6% higher than FH-689. Compared to control, S at 75 kg S ha-1 increased oil yield of FH-331 by 22% whereas S at 50 kg ha-1 increased oil yield by 23% of FH-689. Seed samples were analysed for different biodiesel quality parameters. The ranges of all quality parameters of sunflower biodiesel such as viscosity, calorific values, acid value, iodine value, saponification value, cetane number, and pour point were in ASTM standard range. We conclude that sunflower is a promising and sustainable option for producing biodiesel, the potential of which can be increased by optimal S management under field conditions.