Embryotoxic effects of Ciprofloxacin in Chicken: A potential risk for antibiotic resistance

Background: Ciprofloxacin is considered as a relatively safe drug having broad spectrum antimicrobial activity in humans and animals including poultry, besides its reported cartilage damage in children and debated use in pregnancy.Methods: Current study is designed to highlight the embryotoxic effects of ciprofloxacin in chicken. In the study fertilized eggs were categorized in 5 groups incubated at standard parameters. On 4th day of incubation, group1 and 2 were injected with Ciprofloxacin (30 and 60 mg/egg respectively). Group 3 was pinched with needle only and group 4 was injected with sterilized saline solution. Group 5 was kept as a control, without any injection or pinching.Results: On the 18th day of incubation, the growth of embryos was monitored. Hemorrhages on neck and head areas were noticed in treated group treated with 60 mg/egg. Low body weight along with the defective beak and nail formation was noticed. No other clear external deformity was observed in any treated and normal groups. It can be inferred that embryotoxic effects of ciprofloxacin cannot be ignored. High or repeated doses can reduce the turnover number of successful hatching chicks and the consumption of antibiotics treated chicken can lead to the development of antimicrobial resistance in humans.Conclusion: It can be concluded that recommended dose limit is very important to avoid the harmful effect of antibiotics and chemicals. Embryotoxic effect of ciprofloxacin cannot be ignored. Use of antibiotic/s in poultry and live stocks should be carefully monitored and judged on medical basis; also its use for growth promotion should be discontinued.Keywords: Ciprofloxacin; Poultry; Antibiotic resistance; Embryotoxic effects; Antimicrobial activity 

Identification of a Novel Mutation in Codon 31 of Kirstein Rat Sarcoma Viral Oncogene Homologue in Colon Cancer: Another Evidence of Non-Canonical Mutational Pathway

Abstract.-Colorectal cancer (CRC) is a disease of the large intestine and regarded as a multistep process resulting from accumulation of different genetic alterations like activation of proto-oncogenes and inactivation of tumour suppressor genes. Kirstein rat sarcoma viral oncogene homologue (K ras) is a proto-oncogene and mutations in this gene are considered to be involved in the early transition from normal colonic epithelium to premalignant tissue. Mutations at codon 12, 13, and 61 are widely studied and considered to be responsible to account for most Rasmediated carcinogenesis but some of the recent evidences have suggested that non canonical mutations (outside of codons 12, 13, and 61) may also contribute to the genetic aberrations leading to the Ras-associated oncogenesis. We have analyzed the whole coding region of the gene and report a non-canonical novel heterozyogous mutation at codon 31 in a colonic tumor. Polymerase Chain Reaction (PCR)-Denaturing Gradient Gel Electrophoresis (DGGE), subsequent sequencing data revealed, G to A transition at first base of codon substituting glutamic acid (GAA) to lysine (AAA). Since this mutation has never been reported before in CRC, it is a novel variant in K ras

願書留（正月より十二月まで、名主上野新右衛門外）

Few quantifiable tissue biomarkers for the diagnosis and prognosis of prostate cancer exist. Using an unbiased, quantitative approach, this study evaluates the potential of three proteins of the 40S ribosomal protein complex as putative biomarkers of malignancy in prostate cancer. Prostate tissue arrays, constructed from 82 patient samples (245 tissue cores, stage pT3a or pT3b), were stained for antibodies against three ribosomal proteins, RPS19, RPS21 and RPS24. Semi-automated Ox-DAB signal quantification using ImageJ software revealed a significant change in expression of RPS19, RPS21 and RPS24 in malignant vs non-malignant tissue (p<0.0001). Receiver operating characteristics curves were calculated to evaluate the potential of each protein as a biomarker of malignancy in prostate cancer. Positive likelihood ratios for RPS19, RPS21 and RPS24 were calculated as 2.99, 4.21, and 2.56 respectively, indicating that the overexpression of the protein is correlated with the presence of disease. Triple-labelled, quantitative, immunofluorescence (with RPS19, RPS21 and RPS24) showed significant changes (p<0.01) in the global intersection coefficient, a measure of how often two fluorophore signals intersect, for RPS19 and RPS24 only. No change was observed in the co-localization of any other permutations of the three proteins. Our results show that RPS19, RPS21 or RPS24 are upregulated in malignant tissue and may serve as putative biomarkers for prostate cancer

Bi-allelic variants in OGDHL cause a neurodevelopmental spectrum disease featuring epilepsy, hearing loss, visual impairment, and ataxia

The 2-oxoglutarate dehydrogenase-like (OGDHL) protein is a rate-limiting enzyme in the Krebs cycle that plays a pivotal role in mitochondrial metabolism. OGDHL expression is restricted mainly to the brain in humans. Here, we report nine individuals from eight unrelated families carrying bi-allelic variants in OGDHL with a range of neurological and neurodevelopmental phenotypes including epilepsy, hearing loss, visual impairment, gait ataxia, microcephaly, and hypoplastic corpus callosum. The variants include three homozygous missense variants (p.Pro852Ala, p.Arg244Trp, and p.Arg299Gly), three compound heterozygous single-nucleotide variants (p.Arg673Gln/p.Val488Val, p.Phe734Ser/p.Ala327Val, and p.Trp220Cys/p.Asp491Val), one homozygous frameshift variant (p.Cys553Leufs∗16), and one homozygous stop-gain variant (p.Arg440Ter). To support the pathogenicity of the variants, we developed a novel CRISPR-Cas9-mediated tissue-specific knockout with cDNA rescue system for dOgdh, the Drosophila ortholog of human OGDHL. Pan-neuronal knockout of dOgdh led to developmental lethality as well as defects in Krebs cycle metabolism, which was fully rescued by expression of wild-type dOgdh. Studies using the Drosophila system indicate that p.Arg673Gln, p.Phe734Ser, and p.Arg299Gly are severe loss-of-function alleles, leading to developmental lethality, whereas p.Pro852Ala, p.Ala327Val, p.Trp220Cys, p.Asp491Val, and p.Arg244Trp are hypomorphic alleles, causing behavioral defects. Transcript analysis from fibroblasts obtained from the individual carrying the synonymous variant (c.1464T>C [p.Val488Val]) in family 2 showed that the synonymous variant affects splicing of exon 11 in OGDHL. Human neuronal cells with OGDHL knockout exhibited defects in mitochondrial respiration, indicating the essential role of OGDHL in mitochondrial metabolism in humans. Together, our data establish that the bi-allelic variants in OGDHL are pathogenic, leading to a Mendelian neurodevelopmental disease in humans

Socio-economic effects of COVID-19 – a study of the University students and teachers in Pakistan

Background: Coronavirus Disease-2019 (COVID–19) has appeared as a deadly pandemic affecting most of the countries across the world. The disease has caught humanity unprepared; therefore, there has been a lack of awareness about the causes, and transmission and mortality rates. It has also affected the overall socioeconomics from individual to worldwide levels. COVID-19 is an unprecedented and first-time challenge for Pakistan and a lockdown imposed by the Government of Pakistan has further devastated the economy of the country. This online survey was conducted to know the effects of the Covid-19 pandemic on the social life and economic status of the people of Pakistan. In this article, we mainly focused on teachers and students from different Universities of Pakistan for data generation because they can provide better information due to the use of modern technologies as a source of information.Methods: An online questionnaire survey covering 11 parameters including age, gender, employment status, mortality rate, education, marital status and, information about the pathogen responsible for the disease was filled by 1260 individuals from Pakistan.Results: The results obtained show that 56.6% of the responders were males,43.4% were females, 59.9% were unmarried, 37.7% were graduate students and, 48.7% unemployed. Most of the responders (55.6%) said that COVID-19 negatively affected the jobs of the people. We found (93%) of the responders with good knowledge about COVID-19.Conclusion: We conclude from the results that most of the responders were males, educated and they knew the pathogenic effect of the COVID-19 virus on humans. These results also show that the disease has drastically affected the economy and social life of the people of Pakistan.Keywords: Coronavirus; COVID-19; Knowledge; Socio-economic; Pakistan

Origin, Potential Therapeutic Targets and Treatment for Coronavirus Disease (COVID-19)

he ongoing episode of coronavirus disease 19 (COVID-19) has imposed a serious threat to global health and the world economy. The disease has rapidly acquired a pandemic status affecting almost all populated areas of the planet. The causative agent of COVID-19 is a novel coronavirus known as SARS-CoV-2. The virus has an approximate 30 kb single-stranded positive-sense RNA genome, which is 74.5% to 99% identical to that of SARS-CoV, CoV-pangolin, and the coronavirus the from horseshoe bat. According to available information, SARS-CoV-2 is inferred to be a recombinant virus that originated from bats and was transmitted to humans, possibly using the pangolin as the intermediate host. The interaction of the SARS-CoV-2 spike protein with the human ACE2 (angiotensin-converting enzyme 2) receptor, and its subsequent cleavage by serine protease and fusion, are the main events in the pathophysiology. The serine protease inhibitors, spike protein-based vaccines, or ACE2 blockers may have therapeutic potential in the near future. At present, no vaccine is available against COVID-19. The disease is being treated with antiviral, antimalarial, anti-inflammatory, herbal medicines, and active plasma antibodies. In this context, the present review article provides a cumulative account of the recent information regarding the viral characteristics, potential therapeutic targets, treatment options, and prospective research questions

Research trends in rabies vaccine in the last three decades: a bibliometric analysis of global perspective

Introduction Rabies is an infectious zoonotic viral disease which mainly occurs in Africa and Asia. Dogs are predominantly responsible for rabies transmission contributing up to 99% of all human rabies cases. Rabies is a vaccine preventable disease in both animals and humans. Objective This study aimed to quantify and characterize the scientific literature and identify the top most cited studies in rabies vaccine research (RVR) from 1991 to 2020. Methods The data used in this study were downloaded from Web of Science Core Collection (WoSCC), Science Citation Index-Expanded (SCI-E) database. Network visualization analysis was performed using VOSviewer software. Results A total of 1,042 papers (article: n = 986, 94.6%, review: n = 56, 5.4%) were included in this study. These have been cited 17,390 times with an average citation per paper was 16.69 times. The most frequent publication year was 2019 (n = 75, 7.2%). More than 55% studies were published from the United State of America (USA) (n = 380, 36.5%), France (n = 128, 12.3%), and China (n = 97, 9.3%). The most studied Web of Science (WoS) category was immunology (n = 344, 33%). The most prolific author in RVR was Rupprecht CE (n = 55, 5.3%). ‘Vaccine’ was the leading journal (n = 218, 20.9%). Rabies was the most widely used keyword. Conclusion Abundant literature has been published on RVR in developed countries. This study might provide a reference to understand the current and future research trends in RVR. In developing countries research collaboration and co-operation among institutes and researchers needs to be strengthened with developed countries

In Vivo Assessment of the Ameliorative Impact of Some Medicinal Plant Extracts on Lipopolysaccharide-Induced Multiple Sclerosis in Wistar Rats

Multiple sclerosis is a chronic autoimmune disorder that leads to the demyelination of nerve fibers, which is the major cause of non-traumatic disability all around the world. Herbal plants Nepeta hindustana L., Vitex negundo L., and Argemone albiflora L., in addition to anti-inflammatory and anti-oxidative effects, have shown great potential as neuroprotective agents. The study was aimed to develop a neuroprotective model to study the effectiveness of herbal plants (N. hindustana, V. negundo, and A. albiflora) against multiple sclerosis. The in vivo neuroprotective effects of ethanolic extracts isolated from N. hindustana, V. negundo, and A. albiflora were evaluated in lipopolysaccharides (LPS) induced multiple sclerosis Wistar rat model. The rat models were categorized into seven groups including group A as normal, B as LPS induced diseased group, while C, D, E, F, and G were designed as treatment groups. Histopathological evaluation and biochemical markers including stress and inflammatory (MMP-6, MDA, TNF-α, AOPPs, AGEs, NO, IL-17 and IL-2), antioxidant (SOD, GSH, CAT, GPx), DNA damage (Isop-2α, 8OHdG) as well as molecular biomarkers (RAGE, Caspase-8, p38) along with glutamate, homocysteine, acetylcholinesterase, and myelin binding protein (MBP) were investigated. The obtained data were analyzed using SPSS version 21 and GraphPad Prism 8.0. The different extract treated groups (C, D, E, F, G) displayed a substantial neuroprotective effect regarding remyelination of axonal terminals and oligodendrocytes migration, reduced lymphocytic infiltrations, and reduced necrosis of Purkinje cells. The levels of stress, inflammatory, and DNA damage markers were observed high in the diseased group B, which were reduced after treatments with plant extracts. The antioxidant activity was significantly reduced in diseased induced group B, however, their levels were raised after treatment with plant extract. Group F (a mélange of all the extracts) showed the most significant change among all other treatment groups (C, D, E, G). The communal dose of selected plant extracts regulates neurodegeneration at the cellular level resulting in restoration and remyelination of axonal neurons. Moreover, 400 mg/kg dose of three plants in conjugation (Group F) were found to be more effective in restoring the normal activities of all measured parameters than independent doses (Group C, D, E) and is comparable with standard drug nimodipine (Group G) clinically used for the treatment of multiple sclerosis. The present study, for the first time, reported the clinical evidence of N. hindustana, V. negundo, and A. albiflora against multiple sclerosis and concludes that all three plants showed remyelination as well neuroprotective effects which may be used as a potential natural neurotherapeutic agent against multiple sclerosis

Nanoparticles in Drug Delivery: From History to Therapeutic Applications

Current research into the role of engineered nanoparticles in drug delivery systems (DDSs) for medical purposes has developed numerous fascinating nanocarriers. This paper reviews the various conventionally used and current used carriage system to deliver drugs. Due to numerous drawbacks of conventional DDSs, nanocarriers have gained immense interest. Nanocarriers like polymeric nanoparticles, mesoporous nanoparticles, nanomaterials, carbon nanotubes, dendrimers, liposomes, metallic nanoparticles, nanomedicine, and engineered nanomaterials are used as carriage systems for targeted delivery at specific sites of affected areas in the body. Nanomedicine has rapidly grown to treat certain diseases like brain cancer, lung cancer, breast cancer, cardiovascular diseases, and many others. These nanomedicines can improve drug bioavailability and drug absorption time, reduce release time, eliminate drug aggregation, and enhance drug solubility in the blood. Nanomedicine has introduced a new era for drug carriage by refining the therapeutic directories of the energetic pharmaceutical elements engineered within nanoparticles. In this context, the vital information on engineered nanoparticles was reviewed and conferred towards the role in drug carriage systems to treat many ailments. All these nanocarriers were tested in vitro and in vivo. In the coming years, nanomedicines can improve human health more effectively by adding more advanced techniques into the drug delivery system