Industrially Important Fungal Carotenoids: Advancements in Biotechnological Production and Extraction.

Carotenoids are lipid-soluble compounds that are present in nature, including plants and microorganisms such as fungi, certain bacteria, and algae. In fungi, they are widely present in almost all taxonomic classifications. Fungal carotenoids have gained special attention due to their biochemistry and the genetics of their synthetic pathway. The antioxidant potential of carotenoids may help fungi survive longer in their natural environment. Carotenoids may be produced in greater quantities using biotechnological methods than by chemical synthesis or plant extraction. The initial focus of this review is on industrially important carotenoids in the most advanced fungal and yeast strains, with a brief description of their taxonomic classification. Biotechnology has long been regarded as the most suitable alternative way of producing natural pigment from microbes due to their immense capacity to accumulate these pigments. So, this review mainly presents the recent progress in the genetic modification of native and non-native producers to modify the carotenoid biosynthetic pathway for enhanced carotenoid production, as well as factors affecting carotenoid biosynthesis in fungal strains and yeast, and proposes various extraction methods to obtain high yields of carotenoids in an attempt to find suitable greener extraction methods. Finally, a brief description of the challenges regarding the commercialization of these fungal carotenoids and the solution is also given.

In Silico Designing of Thieno[2,3-b]thiophene Core-Based Highly Conjugated, Fused-Ring, Near-Infrared Sensitive Non-fullerene Acceptors for Organic Solar Cells.

The performance of organic solar cells (OSCs) has been improving steadily over the last few years, owing to the optimization of device fabrication, fine-tuning of morphology, and thin-film processing. Thiophene core containing fused ring-type non-fullerene acceptors (NFAs) achieved significant proficiency for highly efficient OSCs. Quantum chemical computations are utilized herein with the motive of suggesting new NIR sensitive, highly efficient low-band gap materials for OSCs. A series of extended conjugated A-π-D-π-A architectured novel fused-ring NFAs (FUIC-1-FUIC-6) containing thieno[2,3-b]thiophene-based donor core are proposed by substituting the end-capped units of synthesized molecule F10IC. Different properties including frontier molecular orbital analysis, density of states analysis, transition density matrix analysis, excitation energy, reorganizational energies of both holes (λh) and electrons (λe), and open-circuit voltage (V oc) were performed employing the density functional theory approach. Charge transfer analysis of the best-designed molecule with the donor complex was analyzed to comprehend the efficiency of novel constructed molecules (FUIC-1-FUIC-6) and compared with the reference. End-caped acceptor alteration induces the reduction of the energy gap between HOMO-LUMO (1.88 eV), tunes the energy levels, longer absorption in the visible and near-infrared regions, larger V oc, smaller reorganizational energies, and binding energy values in designed structures (FUIC-1-FUIC-6) in comparison to reference (FUIC). The designed molecules show the best agreement with the PTBT-T donor polymer blend and cause the highest charge from the HOMO to the LUMO orbital. Our findings predicted that thieno[2,3-b] thiophene-based newly designed molecules would be efficient NFAs with outstanding photovoltaic characteristics and can be used in future applications of OSCs.

Clinical and Epidemiological Spectrum of Acute Viral Hepatitis Due to Hepatitis A and E in Children: A Descriptive, Cross-Sectional, Hospital-Based Study.

OBJECTIVE: Acute viral hepatitis (AVH) in children is a serious and major public health concern globally and in developing countries such as Pakistan. We conducted this study to determine the clinical and epidemiological spectrum of AVH due to hepatitis A virus (HAV) and hepatitis E virus (HEV) infection in children. METHODOLOGY: This cross-sectional study was conducted at the Pediatric Medicine Department of a tertiary care hospital from February 20, 2020, to February 20, 2022. A total of 200 children 1-12 years of age who presented with symptoms and signs of AVH were enrolled. Demographic and clinical characteristics were noted, and venous blood was drawn for the assessment of HAV IgM and HEV IgM using an enzyme-linked immunosorbent assay (ELISA). Descriptive statistics are run, and the results are presented as tables. RESULTS: Of the children, 75% were diagnosed with acute HAV infection. The median duration of illness was six days (range: 2-21 days). The most common age group affected was 6-10 years (43.5%), of which 56.5% were males. Most of the children belonged to low and middle socioeconomic status (86.5%), and 41.5% consumed underground water for drinking. Fever was the most common symptom, followed by appetite loss and yellow discoloration of urine. Alanine aminotransferase (ALT) was significantly high in HEV compared to HAV infection (2060.2±1036.7 versus 1730.7±957.5 IU/L) (P=0.04). CONCLUSION: Acute HAV was more prevalent. Those who are male, 6-10 years of age, from lower and middle socioeconomic status, and using underground drinking water were more affected by acute viral hepatitis. The clinical and biochemical presentation of HAV and HEV did not differ significantly.

Phytochemical analysis of Berberis lyceum methanolic extract and its antiviral activity through the restoration of MAPK signaling pathway modulated by HCV NS5A

Objective: To evaluate the antiviral activity and phytochemicals of selected plant extracts and their effect on the mitogen-activated protein kinase (MAPK) signaling pathway modulated by hepatitis C virus (HCV) nonstructural protein 5A (NS5A). Methods: A total of ten plant extracts were initially screened for their toxicities against HepG2 cells. The non-toxic plants were tested for their inhibitory effect on the expression of HCV NS5A at both mRNA and protein levels using real-time PCR and Western blotting assays, respectively. The differential expression of the genes associated with MAPK pathway in the presence of NS5A gene and plant extract was measured through real-time PCR. Subsequently, the identification of secondary metabolites was carried out by phytochemical and HPLC analysis. Results: The phytochemical profiling of Berberis lyceum revealed the presence of alkaloids, phenols, saponins, tannins, flavonoids, carbohydrates, terpenoids, steroids, and glycosides. Similarly, quercetin, myricetin, gallic acid, caffeic acid, and ferulic acid were identified through HPLC analysis. The methanolic extract of Berberis lyceum strongly inhibited HCV RNA replication with an IC50 of 11.44 μg/mL. RT-PCR and Western blotting assays showed that the extract reduced the expression of HCV NS5A in a dose-dependent manner. Berberis lyceum extract also attenuated NS5A-induced dysregulation of the MAPK signaling pathway. Conclusions: Our findings suggest that Berberis lyceum extract strongly inhibits HCV propagation by reducing HCV NS5A-induced perturbation of MAPK signaling.

One-Pot Synthesis of Heterobimetallic Metal-Organic Frameworks (MOFs) for Multifunctional Catalysis.

A one-pot synthesis of bimetallic metal-organic frameworks (Co/Fe-MOFs) was achieved by treating stoichiometric amounts of Fe and Co salts with 2-aminoterephthalic acid (NH2 -BDC). Monometallic Fe (catalyst A) and Co (catalyst F) were also prepared along with mixed-metal Fe/Co catalysts (B-E) by changing the Fe/Co ratio. For mixed-metal catalysts (B-E) SEM energy-dispersive X-ray (EDX) analysis confirmed the incorporation of both Fe and Co in the catalysts. However, a spindle-shaped morphology, typically known for the Fe-MIL-88B structure and confirmed by PXRD analysis, was only observed for catalysts A-D. To test the catalytic potential of mixed-metal MOFs, reduction of nitroarenes was selected as a benchmark reaction. Incorporation of Co enhanced the activity of the catalysts compared with the parent NH2 -BDC-Fe catalyst. These MOFs were also tested as electrocatalysts for the oxygen evolution reaction (OER) and the best activity was exhibited by mixed-metal Fe/Co-MOF (Fe/Co batch ratio=1). The catalyst provided a current density of 10 mA cm-2 at 410 mV overpotential, which is comparable to the benchmark OER catalyst (i.e., RuO2 ). Moreover, it showed long-term stability in 1 m KOH. In a third catalytic test, dehydrogenation of sodium borohydride showed high activity (turnover frequency=87 min-1 ) and hydrogen generation rate (67 L min-1 g-1 catalyst). This is the first example of the synthesis of bimetallic MOFs as multifunctional catalysts particularly for catalytic reduction of nitroarenes and dehydrogenation reactions.

A trinuclear cobalt-based coordination polymer as an efficient oxygen evolution electrocatalyst at neutral pH.

The dearth of an efficient, robust, abundant and cost-effective water oxidation catalyst is debatably the major hurdle for the technological advancement of artificial photosynthesis devices. Herein, a three dimensional (3D) cobalt-based coordination polymer {[Co3(pyz)(fa)3(dmso)2]·2H2O}n, (1) (pyz = pyrazine, fa = fumarate, dmso = dimethyl sulfoxide) has been synthesized and demonstrated to act as an efficient electrocatalyst towards water oxidation at neutral pH. Compound 1 displays a stair-like arrangement parallel to the b-axis, with the cobalt clusters arranged in a zigzag fashion, and contains small, honeycomb-like channels parallel to the c-axis. Compound 1 shows a remarkable activity for water oxidation and attains a current density of 1 mA.cm-2 at low overpotential (η = 257 mV) with a Tafel slope value of 80.5 mV.dec-1. This high performance of 1 in catalysing the water oxidation reaction is attributed to its unique 3-D architecture. The results of electrochemical investigations, including long-term and controlled potential electrolysis, are anticipated to guide the forthcoming advancement in creating efficient, cheap and noble metal (Pt/Ru/Ir) free catalysts for the water oxidation reaction.

Combinatorial effect of curcumin and tumor necrosis factor-α-related apoptosis-inducing ligand (TRAIL) in induction of apoptosis via inhibition of nuclear factor kappa activity and enhancement of caspase-3 activity in chronic myeloid cells: An In-vitro study.

BACKGROUND: Nuclear factor kappa B (NFkB-light-chain-enhancer of activated B-cells) expression and its regulation is a key role in the development of number of malignancies, as NFkB mediates the balance between cell death and its survival. Therefore, NFkB regulation constitutes an attractive target to overcome the resistance to chemotherapeutic agents in anticancer therapy. Curcumin, as a chemopreventive agent, has a potential role in inhibiting cell growth in a variety of malignancies. Thus, this study was aimed to investigate the efficacy of curcumin along with tumor necrosis factor-α-related apoptosis-inducing ligand (TRAIL) in KCL-22 myeloid cells along with an investigation of the mechanism by which both the agents exert their effects. MATERIALS AND METHODS: KCL-22 cells were exposed to different doses of curcumin and TRAIL alone and in combination. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, caspase activity by fluorescent method, protein expression by western Blot, and NFkB activity by electrophoretic mobility shift assays, respectively. RESULTS: Cell viability assay revealed that when both the agents, curcumin and TRAIL, were used together, there was reduced cell viability in dose- and time-dependent manner as compared to each agent alone. Curcumin and TRAIL enhanced the caspase-3 activity as compared to caspase-8 and caspase-9. Both the agents induced apoptosis in KCL-22 cells by suppressing the IκB kinase and NFkB activity. CONCLUSION: Our results conclude that curcumin and TRAIL effectively induce the apoptosis through the inhibition of NFkB activity and by enhancing the caspase-3 activity. Thus, curcumin may prove as a potent inhibitor of NFkB by representing its role in cancer pathogenesis, especially in chronic myeloid leukemia cells.

Ionic liquid as a potential solvent for preparation of collagen-alginate-hydroxyapatite beads as bone filler.

In this study, collagen/alginate/hydroxyapatite beads having different proportions were prepared as bone fillers for the restoration of osteological defects. Ionic liquid was used to dissolve the collagen and subsequently the solution was mixed with sodium alginate solution. Hydroxyapatite was added in different proportions, with the rationale to enhance mechanical as well as biological properties. The prepared solutions were given characteristic bead shapes by dropwise addition into calcium chloride solution. The prepared beads were characterized using FTIR, XRD, TGA and SEM analysis. Microhardness testing was used to evaluate the mechanical properties. The prepared beads were investigated for water adsorption behavior to ascertain its ability for body fluid uptake and adjusted accordingly to the bone cavity. Drug loading and subsequently the antibacterial activity was investigated for the prepared beads. The biocompatibility was assessed using the hemolysis testing and cell proliferation assay. The prepared collagen-alginate-HA beads, having biocompatibility and good mechanical properties, have showed an option of promising biologically active bone fillers for bone regeneration.

Leptin as a Predictive Marker in Unexplained Infertility in North Indian Population.

INTRODUCTION: According to WHO, the primary infertility in India is about 3.9% (age-standardized to 25-49 year) and 16.8% (age-standardized to 15-49 year), using the "age but no birth" definition. Several factors which affect fertility include low sperm production in men, poor egg quality and blocked fallopian tubes in women and also hormonal imbalances. Leptin plays a critical role in women's reproduction and neuroendocrine health. It is used for treating exercise-induced bone loss, eating disorders and infertility. AIM: To evaluate the serum leptin levels in Indians and to ascertain the relationship between serum leptin levels, Unexplained Infertility (UI) and related variables [height, weight, Waist Hip Ratio (WHR), Body Mass Index (BMI)] between obese infertile, non-obese infertile and healthy subjects. MATERIALS AND METHODS: The present case-control study was conducted at the Department of Obstetrics and Gynaecology, King George's Medical University (KGMU), Lucknow, India and funded by Department of Science and Technology, New Delhi, India. The study included 229 female participants in the age group of 18-40 years (120 cases and 109 controls) who were randomly selected. The blood samples were collected from the Infertility Clinic, Queen Mary's Hospital, KGMU, Lucknow, India. All the participants underwent complete physical examination. Initially, the participants were categorized into fertile and infertile groups, they were further divided on the basis of BMI, normal (BMI- 18.5-24.5) and overweight or obese (BMI≥25). Leptin level was measured by Active Human Leptin ELISA kit and BMI of all subjects was calculated in kg/m2 (weight in kg and height in m). RESULTS: A highly positive linear correlation (R=0.754, p<0.001) was found between BMI and serum leptin in unexplained infertile women, which indicates a strong relationship between BMI and serum leptin. The variation in serum leptin is explained by the independent variable, BMI. There was a partial positive linear correlation between BMI and serum leptin in the control group. Statistically there was no significant correlation (R=0.109, p=0.258) between BMI and serum leptin in the control group. CONCLUSION: The present study clearly demonstrates that level of leptin is higher in unexplained infertile than in the fertile group, and also shows that a strong relationship exists between BMI and serum leptin in the obese group. Serum leptin level was significantly higher in obese than non-obese subjects. Thus, leptin is an important factor for normal reproductive function. Obesity, the main cause of infertility may be controlled by regulating the leptin concentration.

Antiproliferative and Apoptotic Effect of Curcumin and TRAIL (TNF Related Apoptosis inducing Ligand) in Chronic Myeloid Leukaemic Cells.

INTRODUCTION: Curcumin, traditionally utilized as a flavouring zest as a part of Indian cooking, has been accounted to decrease the proliferation potential of most cancer cells. Apoptosis is a mechanism by which most anticancer therapies including chemotherapy, radiation and antihormonal therapy kill tumour/cancer cells. Novel agents that may sensitize drug-resistant tumour cells for induction of apoptosis by customary treatments could lead to the regression and improved prognosis of the refractory disease. Indeed, chemotherapeutic agents have been shown to sensitize cancer cells to killing by death ligands such as tumour necrosis factor-α. AIM: To investigate cytotoxicity and apoptotic effect of curcumin in chronic myeloid leukaemic cell line KCL-22. MATERIALS AND METHODS: In present study, different doses of curcumin (10,25,50,75,100µM) and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) (25,50 µM) alone and combine regimen were exposed to myeloid leukaemic cell KCL-22. The cell viability was monitored by MTT assay, apoptotic activity by binding of Annexin V-FITC using fluorescence microscopy and cell cycle check points by flow cytometry. RESULTS: Cytotoxic assay revealed that curcumin and TRAIL induced both dose and time-dependent decrease in cell viability. Significant cell cytotoxicity was seen in combine regimen of both curcumin and TRAIL at 48 h of exposure. Cells treated with curcumin and TRAIL was arrested at the S phase, as revealed by flow cytometric analysis. Subtoxic concentrations of the curcumin-TRAIL combination induced strong apoptotic response in KCL-22 cells as demonstrated by the binding of Annexin V-FITC. CONCLUSION: Our study conclude that curcumin inhibits the cancer cell growth by inducing apoptosis and enhance the therapeutic potential of TRAIL which recommends that both curcumin alone or in combination with TRAIL might be useful for leukaemic prevention and better therapeutic responses.

The role of Wnt signaling pathway in carcinogenesis and implications for anticancer therapeutics.

The Wnt proteins are a family of 19 secreted glycoproteins that occupy crucial roles in the regulation of processes such as cell survival, proliferation, migration and polarity, cell fate specification, body axis patterning and self-renewal in stem cells. The canonical pathway has been implicated in a variety of cancers. As such, it is only fair to conclude that therapies targeting the Wnt pathway may play an essential role in the future of anticancer therapeutics, both alone or in conjunction with traditional therapies.

Reasons for non-vaccination in pediatric patients visiting tertiary care centers in a polio-prone country.

BACKGROUND: The Expanded Program on Immunization (EPI) was initiated by World Health Organization (WHO) in 1974 in order to save children from life threatening, disabling vaccine-preventable diseases (VPDs). In Pakistan, this program was launched in 1978 with the main objectives of eradicating polio by 2012, eliminating measles and neonatal tetanus by 2015, and minimizing the incidence of other VPDs. However, despite the efforts of government and WHO, this program has not received the amount of success that was desired. Hence, the objectives of this study were to elucidate the main reasons behind not achieving the full immunization coverage in Pakistan, the awareness of children's attendant about the importance of vaccination, their attitudes, thoughts and fears regarding childhood immunization, and the major hurdles faced in pursuit of getting their children vaccinated. METHODS: This was an observational, cross-sectional, questionnaire-based study conducted during a one year period from 4th January, 2012 to 6th January, 2013 at the pediatric outpatient clinics of Civil Hospital (CHK) and National Institute of Child Health (NICH). We attempted to interview all the parents who could be approached during the period of the study. Thus, convenience sampling was employed. The parents were approached in the clinics and interviewed after seeking informed, written consent. Those patients who were not accompanied by either of their parents were excluded from the study. The study instrument comprised of three sections. The first section consisted was concerned with the demographics of the patient and the parents. The second section dealt with the reasons for complete vaccination or under-vaccination. The last section aimed to assess the knowledge, attitudes and beliefs of the respondents. RESULTS: Out of 1044 patients, only 713(68.3%) were fully vaccinated, 239(22.9%) were partially vaccinated while 92(8.8%) had never been vaccinated. The vaccination status showed statistically significant association with ethnicity, income, residence, number of children and paternal occupation (p < 0.05 for all). The most common provocative factor for vaccination compliance was mass media (61.9%). The most common primary reason for non-vaccination was lack of knowledge (18.1%), whereas the most common secondary reason for non-vaccination was religious taboos (31.4%). Majority of the respondents demonstrated poor knowledge of EPI schedules or VPDs. However, most believed that there was a need for more active government/NGO involvement in this area. CONCLUSION: The most common primary reason for non-vaccination, i.e. lack of knowledge, and the most common secondary reason, i.e. religious taboos, imply that there is dire need to promote awareness among the masses in collaboration with NGOs, and major religious and social organizations.

(5Z)-5-(2-Hydroxy-benzyl-idene)-2-thioxo-1,3-thia-zolidin-4-one methanol hemisolvate.

In the title compound, C(10)H(7)NO(2)S(2)·0.5CH(3)OH, the dihedral angle between the aromatic rings is 11.43 (11)° and a short intra-molecular C-H⋯S contact occurs. The methanol solvent mol-ecule is equally disordered over two sets of sites. In the crystal, inversion dimers linked by pairs of N-H⋯O hydrogen bonds occur. The methanol solvent mol-ecule connects the dimers through O-H⋯S and O-H⋯O inter-molecular hydrogen bonds. Further stability is afforded by C-H⋯π and π-π inter-actions [centroid-centroid separation = 3.5948 (13) Å].

(5Z)-5-(2-Hydroxy-benzyl-idene)-3-phenyl-2-thioxo-1,3-thia-zolidin-4-one.

In the title compound, C(16)H(11)NO(2)S(2), the dihedral angles between the heterocyclic ring and the phenyl and anilinic benzene rings are 9.68 (13) and 79.26 (6)°, respectively, and an intra-molecular C-H⋯S inter-action occurs. In the crystal, inversion dimers linked by pairs of O-H⋯O hydrogen bonds occur, leading to R(2) (2)(10) loops, and C-H⋯O and weak C-H⋯π inter-actions further consolidate the packing.

(5Z)-5-(2-Methyl-benzyl-idene)-3-phenyl-2-thioxo-1,3-thia-zolidin-4-one.

In the title compound, C(17)H(13)NOS(2), the heterocyclic ring is oriented at a dihedral angle of 74.43 (5)° with respect to the anilinic benzene ring and at a dihedral angle of 17.31 (9)° with respect to phenyl ring. An intra-molecular C-H⋯S inter-action occurs, resulting in an S(6) ring. In the crystal, the packing is consolidated by C-H⋯π inter-actions and possible very weak aromatic π-π stacking [centroid-centroid separation = 4.025 (1) Å].