Labetalol is a medication used to treat maternal hypertension during pregnancy. However, it is often associated with many side effects. Recently, several studies have been focused on the protective effect of medicinal plant extracts, such as ginger, against drugs inducing toxicity. Therefore, it has been hypothesized that ginger aqueous extraction can ameliorate labetalol-induced histological, ultrastructural changes, DNA damage, and apoptosis in fetal heart tissue. To achieve the aim of this study, sixty pregnant female albino rats were divided into 4 groups (15 each). Group I (Control). Group II received ginger (200 mg/kg). Group III received labetalol (300 mg/kg). Group IV received labetalol first followed by ginger. All groups were orally injected daily during the organogenesis phase of gestation i.e., from the 6th to the 15th day, and sacrificed at the 20th day of gestation. Results showed that labetalol-induced marked histological and ultrastructural alterations. Also, there was severe DNA damage and an increase in the apoptotic rates determined by Annexin-V/PI dual staining assay. Injection of the ginger aqueous extract caused evident improvement in cardiac tissue, DNA damage, and apoptotic rates. In conclusion, the results suggest that ginger extract could be a potential candidate agent for reducing labetalol-induced cardiotoxicity in the fetal heart of albino rats.

Hyaluronic acid (HA) has great importance in biomedical applications. In this work, a novel nanoparticle-based method that stimulates the hyaluronic acid (HA) production by the bacteria Streptococcus equi subsp. Zooepidemicus has been reported. CNTs with diameters of 40-50 nm and lengths of about 20 mm were used at four different concentrations (0, 10, 25, 50, and 100 μg) to the bacteria and determined the mass of the produced HA in dependence on the exposure time under UV-irradiation. The results clearly showed that the exposure for one minute with low power UV light (254 nm) and 100 µg (CNTs) treatments steadily increased HA production from the control (0.062 g/L) to the highest value (0.992) g/L of HA. The incubation of the streptococci with CNTs led to an increase of the HA production by a factor of 4.23 after 300S exposure time under UV light, whereas the HA production was no significant enhancement under visible light. It is explained that the CNTs nanoparticle-stimulated increase of the HA production with the internalization of the nanoparticles by the bacteria since they "serve as co-enzymes" under induced mutation by UV-irradiation. Transformation process was carried out and showed that the major protein band of Streptococcus equi was observed in the Streptococcus DH5α. RAPD analysis indicates that the amplified DNA fragments and the percentage of polymorphism was similar between Streptococcus equi and Streptococcus DH50α. The chemical structure and molecular weight of the photoproduced HA from Streptococcus equi was similar to the chemical structure of the standard sample.

Red beet (Beta vulgaris L.) is commercially grown in Punjab and Khyber Pakhtunkhwa (KPK) regions while cultivated as vegetable in Baluchistan and Sindh regions of Pakistan. It is well known for its health-promoting role in several clinical and pathologic outcome due to abundance of betalains and other bioactive compounds. The purpose of study was to interpret bioactivity of of B. vulgaris leaves (BvLM) and roots (BvRM) extracts for finding natural cure of neurodegenerative diseases (NDs).

Pharmacogenetics is involved in customizing therapy according to the genetic makeup of an individual, and is applicable for chemotherapy, radiotherapy as well as targeted therapy. Drug metabolizing enzymes (DMEs) involving both phase I, and phase II reactions are widely studied. Our study was involved in whole exome sequencing (WES) of cancer patients, followed by analysis for identifying key variations in DMEs, and associated transporters that have a potential impact on treatment outcome.

Faba beans are acknowledged as a good source of proteins, minerals, fibers, vitamins and antioxidants. A blending study was undertaken in order to prepare naturally bread from enriched flours with added nutritional value, mainly in terms of Iron and proteins. Enriched flours were prepared with varied levels (25, 30, 35 and 40%) of whole faba bean flour to assess the effects of this substitution on their nutritional and technological properties. Then, whole durum wheat bread (regular) and enriched bread at 40% substitution level (composite bread) were prepared and subjected to sensory evaluation. The substitution level of composite bread was selected on the basis of Iron and proteins contents and technological results of the flour blends. Nutritionally, except for moisture, fibers, fat, zinc and sodium values, significant (p < 0.05) increases were showed in ash, proteins, minerals, total phenolic compounds, condensed tannins, total flavonoids and anti-radical activity values. Technologically, significant (p < 0.05) decreases were recorded for lightness and whiteness index. The gluten strength value revealed a significant (p < 0.05) decrease as whole faba bean flour was added. On the sensory level, the level of substitution (40%) chosen for the manufacture of composite bread resulted in acceptable bread by consumers. Moreover, composite bread was most preferred in aroma as it imparts a feeling of satiety. The observed nutritional improvements could be useful for malnourished people, including those having Iron and proteins deficiencies. Technologically, the observed changes didn't present limitations since composite bread was accepted by consumers even at 40% substitution level. Besides, the slight preference of composite bread aroma might encourage its consumption by consumers. Also, its promotion of satiety is important for gluten sensitivity sufferers. Our results suggested that 40% is the appropriate ratio to increase, at the same time, Iron and proteins contents of enriched flours as well as their overall nutritional quality. Also it was possible to produce natural composite bread at this level (40%) while maintaining adequate technological and sensory quality.

Iron deficiency anemia (IDA) is the highest nutritional deficiency worldwide. It is a multifactorial disease, with a higher morbidity rate. TMPRSS6 polymorphisms importantly rs855791 is found to play an essential role in iron homeostasis in the human body. The rs855791 (T > C) polymorphism is highly associated with iron levels, and multiple blood parameters, leading to IDA. The role of TMPRSS6 rs855791 polymorphism and the significance of complete blood count (CBC) parameters in the pathogenesis of IDA is not yet studied in the Pakistani population.

To investigate the effect of the ethyl acetate fraction of the aerial parts of E. paralias L. F. Euphorbiaceae on nephroprotective, cytotoxic, and antioxidant.

Ethnobotanical and phytochemical studies are useful to discover new drugs. Phytochemical screening is an important step in the detection of the bioactive components existing in medicinal plants that are used in traditional medicine. Very few phytochemical studies investigating medicinal plants used in traditional medicine exist in Saudi Arabia. Eighty-five medicinal plants used in traditional medicine in Jeddah, Saudi Arabia are investigated here for the first time. This research aims to screen of 85 medicinal plants used in traditional medicine in Jeddah for the presence of secondary metabolites, and to answer the following question: Is the ethnomedicinal importance of medicinal plants used in Jeddah conform to their secondary metabolite content. Ethnobotanical fieldwork took place in Jeddah from August 2018 to September 2019. Eighty-five different plant species belonging to 37 families were identified. Screening of 85 medicinal plants was performed for the presence of alkaloids, glycosides, flavonoids, tannins, saponins and resins using standard methods. The most commonly distributed phytochemical compounds among medicinal plants used were glycosides (82%; 70 species), tannins (68%; 58 species), alkaloids (56%; 48 species), saponins (52%, 44 species) and flavonoids (35%; 30 species). On the other hand, the least commonly distributed compounds were resins (31%; 26 species). All the six groups of secondary metabolites were found in seeds of Cuminum cyminum L., Pimpinella anisum L. and Trigonella foenum-graecum L. It can be said that the ethnomedicinal importance of these 85 medicinal plants used in Jeddah conform to their secondary metabolite content. More research should be carried out on the quantitative analysis of phytochemicals in these 85 medicinal plants used in traditional medicine in Jeddah. Furthermore, there is a need to focus phytochemical screening on ethnobotanical studies to complete research into traditional medicine which leads to the discovery of new drugs.

Breast cancer is a major cause of cancer related deaths in women worldwide. Available treatments pose serious limitations such as systemic toxicity, metastasis, tumor recurrence, off-target effects, and drug resistance. In recent years, phytochemicals such as secondary metabolites due to their effective anticancer potential at very low concentration have gained attention. Aim of the study was to evaluate anticancer potential of Citrullus colocynthis and its possible molecular targets on MCF-7, a human breast cancer cell line. Methanolic extract of leaves was prepared and fractionated by solvents (n-hexane, chloroform, ethyl acetate and n-butanol) with increasing polarity. Bioassays and gene expression regulation was conducted to evaluate the anticancer activity, proliferation rate and cell cycle regulation of breast cancer cells treated with extract and its fractions, separately. Results showed a significant anticancer activity of methanolic extract of C. colocynthis and two of its fractions prepared with chloroform and ethyl acetate. Bioassays depicted significant decrease in proliferation and growth potential along with cell cycle arrest of treated cells compared to control untreated cells. Expression regulation of genes further confirmed the cell cycle arrest through significant upregulation of cyclin-CDK inhibitors (p21 and p27) and cell cycle checkpoint regulators (HUS1, RAD1, ATM) followed by downregulation of downstream cell cycle progression genes (Cyclin A, Cyclin E, CDK2). It is concluded that C. colocynthis arrests cell cycle in human breast cancer cells through expression regulation of cyclin-CDK inhibitors and with further research can be proposed for therapeutic interventions.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is one of the biggest public health issues in the last years. The WHO has reported more than 50,000 confirmed cases and more than 1,000,000 confirmed deaths around the world. Early diagnosis is essential for an appropriate patient care and infection control, so laboratory where molecular tests are held plays a main role. However, laboratory facilities for testing are limited in rural areas. Therefore, it is important to have an effective and practical point-of-care diagnostic system in order to be implemented in developing countries with limited energy access. The objective of this research is to develop an energetically autonomous point-of-care diagnostic system for molecular detection of SARS-CoV-2. This design consists of a retractable system with an area of 15.79 m2 and 3 well-distributed interior areas to guaranty appropriate sample processing. Our point-of-care diagnostic system can be installed at a fixed place (stationary), and it can also be transported to various strategic places (itinerant). The off-grid photovoltaic system feasibility was evaluated using the PVsyst software, presenting an installed capacity of 2.79 KWp, consisting of 4 monocrystalline photovoltaic modules, a 45 A charge regulator and 4 batteries (6 V, 453 Ah). The results showed a performance ratio of 0.522, with higher losses by the full battery (31.77%). This research determines that the proposed point-of-care diagnostic system meets all requirements to set and operate molecular techniques to diagnose infectious diseases, such as COVID-19, with good laboratory conditions, secure and eco-efficient energy, supporting the health scheme to prevent and control the spread of the virus.

This study retroactively investigated the search used in a 2019 review by Hayden et al., one of the first systematic reviews of prognostic factors that was published in the Cochrane Library. The review was designed to address recognized weaknesses in reviews of prognosis by using multiple supplementary search methods in addition to traditional electronic database searching.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), can lead to severe respiratory illness. Patients with underlying comorbidities have a high risk of contracting COVID-19. Therefore, serological assays are urgently needed to diagnose asymptomatic carriers of SARS-CoV-2, to estimate the prevalence of infection, and for disease prevention and control. This study aimed to develop an enzyme-linked immunosorbent assay (ELISA) for the detection of anti-SARS-CoV-2 antibodies in humans.

Human milk is the ideal food for infants due to its unique nutritional and immune properties, and more recently human milk has also been recognized as an important source of bacteria for infants. However, a substantial amount of fundamental human milk microbiome information remains unclear, such as the origin, composition and function of the community and its members. There is emerging evidence to suggest that the diversity and composition of the milk microbiome might differ between lactation stages, due to maternal factors and diet, agrarian and urban lifestyles, and geographical location. The evolution of the methods used for studying milk microbiota, transitioning from culture dependent-approaches to include culture-independent approaches, has had an impact on findings and, in particular, primer selection within 16S rRNA gene barcoding studies have led to discrepancies in observed microbiota communities. Here, the current state-of-the-art is reviewed and emerging frontiers essential to improving our understanding of the human milk microbiome are considered.

Understanding the mechanisms behind lignin formation is an important research area with significant implications for the bioenergy and biomaterial industries. Computational models are indispensable tools for understanding this complex process. Models of the monolignol pathway in Populus trichocarpa and other plants have been developed to explore how transgenic modifications affect important bioenergy traits. Many of these models, however, only capture one level of biological organization and are unable to capture regulation across multiple biological scales. This limits their ability to predict how gene modification strategies will impact lignin and other wood properties. While the first multiscale model of lignin biosynthesis in P. trichocarpa spanned the transcript, protein, metabolic, and phenotypic layers, it did not account for cross-regulatory influences that could impact abundances of untargeted monolignol transcripts and proteins. Here, we present a multiscale model incorporating these cross-regulatory influences for predicting lignin and wood traits from transgenic knockdowns of the monolignol genes. The three main components of this multiscale model are (1) a transcript-protein model capturing cross-regulatory influences, (2) a kinetic-based metabolic model, and (3) random forest models relating the steady state metabolic fluxes to 25 physical traits. We demonstrate that including the cross-regulatory behavior results in smaller predictive error for 23 of the 25 traits. We use this multiscale model to explore the predicted impact of novel combinatorial knockdowns on key bioenergy traits, and identify the perturbation of PtrC3H3 and PtrCAld5H1&2 monolignol genes as a candidate strategy for increasing saccharification efficiencies while reducing negative impacts on wood density and height.

Biotherapeutics, and antimicrobial proteins in particular, are of increasing interest for human medicine. An important challenge in the development of such therapeutics is their potential immunogenicity, which can induce production of anti-drug-antibodies, resulting in altered pharmacokinetics, reduced efficacy, and potentially severe anaphylactic or hypersensitivity reactions. For this reason, the development and application of effective deimmunization methods for protein drugs is of utmost importance. Deimmunization may be achieved by unspecific shielding approaches, which include PEGylation, fusion to polypeptides (e.g., XTEN or PAS), reductive methylation, glycosylation, and polysialylation. Alternatively, the identification of epitopes for T cells or B cells and their subsequent deletion through site-directed mutagenesis represent promising deimmunization strategies and can be accomplished through either experimental or computational approaches. This review highlights the most recent advances and current challenges in the deimmunization of protein therapeutics, with a special focus on computational epitope prediction and deletion tools.

The tumor mutational burden (TMB) is closely related to immunotherapy outcome. However, the cost of TMB detection is extremely high, which limits its use in clinical practice. A new indicator of genomic instability, the average copy number variation (CNVA), calculates the changes of 0.5-Mb chromosomal fragments and requires extremely low sequencing depth.

Defined as helpful live bacteria that can provide medical advantages to the host when administered in tolerable amounts, oral probiotics might be worth considering as a possible preventive or therapeutic modality to mitigate coronavirus disease 2019 (COVID-19) symptom severity. This hypothesis stems from an emerging understanding of the gut-lung axis wherein probiotic microbial species in the digestive tract can influence systemic immunity, lung immunity, and possibly viral pathogenesis and secondary infection co-morbidities. We review the principles underlying the gut-lung axis, examples of probiotic-associated antiviral activities, and current clinical trials in COVID-19 based on oral probiotics.

There is a lack of information concerning mecC clinical methicillin-resistant Staphylococcus aureus (MRSA) strains throughout the world. In the present survey, 345 MRSA strains were characterized by antimicrobial susceptibility testing and staphylococcal cassette chromosome mec element (SCCmec) typing. mecC-positive MRSA isolates were characterized by study of biofilm formability, adhesion and virulence analysis, multilocus sequence typing, accessory gene regulator (agr) typing, S. aureus protein A locus (spa) typing and staphylocoagulase typing. The present study found ten SCCmec types, with the majority being SCCmec type III (38.3%). The presence of mecC was confirmed in three isolates from skin wounds (two isolates) and burn wounds (one isolate). All the mecC-positive isolates carried SCCmec XI and belonged to coa type III. Molecular typing showed that these isolates belonged to clonal complex/ST130-spa type t843-agr type III (two isolates) and clonal complex/ST599-spa type 5930-agr type I. The presence of SCCmec type IV confirms the hypothesis of extensive infiltration from the community to the hospital. Detection of MRSA isolates harbouring the mecC gene highlights the need to perform routine detection methods and molecular investigations in order to identify these emerging strains and limit their transfer in hospitals and communities.

Circular RNA (circRNA) is a novel subclass of noncoding-RNA molecules that participate in development and progression of a variety of human diseases via sponging microRNAs (miRNAs). Until now, the contributions of circRNAs in chemoresistance of hepatocellular carcinoma (HCC) remain largely unknown. In the present study, we aimed to investigate the role of circRNA in cisplatin resistance of HCC. We investigated the expression of circRNAs in 5 paired cisplatin-sensitive and cisplatin-resistant HCC tissues by microarray analysis. The qRT-PCR analysis was to investigate the expression pattern of circARNT2 in HCC patient tissues and cell lines. Then, the effects of circARNT2 on cisplatin resistance, cell proliferation, and apoptosis were assessed in HCC in vitro and in vivo. circARNT2 was significantly upregulated in HCC tissues and cell lines. Overexpression of circARNT2 in HCC was significantly correlated with aggressive characteristics and served as an independent risk factor for overall survival in patients with HCC. In vitro experiments showed that knockdown of circARNT2 inhibited cell proliferation and enhances the cisplatin sensitivity of HCC cells. Furthermore, circARNT2 facilitates HCC progression in vivo. We demonstrated that circARNT2 acts as a sponge for miR-155-5p and verified that PDK1 is a novel target of miR-155-5p. In summary, our study demonstrated that circARNT2 modulates cisplatin resistance through miR-155-5p/PDK1 pathway. Our findings indicated that circARNT2 may serve as a promising therapeutic target for overcoming cisplatin resistance for HCC.

VPS33B is reported to be a tumor suppressor in hepatocellular carcinoma, nasopharyngeal carcinoma, colon cancer, and lung adenocarcinoma. Here, we observed that reduced VPS33B protein level was an unfavorable factor that promoted the pathogenesis of non-small cell lung cancer (NSCLC) in clinical specimens. We achieved lentivirus-mediated stable overexpression of VPS33B in NSCLC cells. Increased VPS33B reduced cell cycle transition and cell proliferation of NSCLC cells in vivo and in vitro. Knocking down VPS33B restored cell growth. Mechanism analysis indicated that miR-192-3p was induced by VPS33B and acted as a tumor suppressor of cell growth in NSCLC. Further, c-Myc or p53 was identified as a transcription factor that bound to the miR-192-3p promoter and regulated its expression. miR-192-3p directly targeted cell cycle-promoted factor CCNB1 and suppressed NSCLC cell growth. VPS33B modulated c-Myc/p53/miR-192-3p signaling to target CCNB1 by reducing activation of the Ras/ERK pathway. Our study reveals a novel molecular basis for VPS33B as a tumor suppressor to participate in the pathogenesis of NSCLC.