Exploring the Potential of Plant Bioactive Compounds against Male Infertility: An In Silico and In Vivo Study.

Infertility is a well-recognized multifactorial problem affecting the majority of people who struggle with infertility issues. In recent times, among infertility cases, the male factor has acquired importance, and now it contributes to approximately half of the infertility cases because of different abnormalities. In the current study, we used natural phytochemicals as potential drug-lead compounds to target different receptor proteins that are involved in the onset of male infertility. A set of 210 plant phytochemicals were docked counter to active site residues of sex hormone-binding globulin, a disintegrin and metalloproteinase 17, and DNase I as receptor proteins. On the basis of binding scores and molecular dynamics simulation, the phytochemicals tricin, quercetin, malvidin, rhamnetin, isorhamnetin, gallic acid, kaempferol, esculin, robinetin, and okanin were found to be the potential drug candidates to treat male infertility. Molecular dynamics simulation showed tricin as a strong inhibitor of all selected receptor proteins because the ligand-protein complexes remained stabilized during the entire simulation time of 100 ns. Further, an in vivo study was designed to evaluate the effect of tricin in male rats with nicotine-induced infertility. It was explored that a high dose of tricin significantly reduced the levels of alanine transaminase, aspartate transaminase, urea, creatinine, cholesterol, triglyceride, and low-density lipoprotein and raised the level of high-density lipoprotein in intoxicated male rats. A high dose of tricin also increased the reproductive hormones (i.e., testosterone, luteinizing hormone, follicle-stimulating hormone, and prolactin) and reduced the level of DHEA-SO4. The phytochemical (tricin, 10 mg/kg body weight) also showed significant improvement in the histo-architecture after nicotine intoxication in rats. From the current study, it is concluded that the phytochemical tricin could serve as a potential drug candidate to cure male infertility.

Immobilization of Aspergillus oryzae tyrosine hydroxylase on ZnO nanocrystals for improved stability and catalytic efficiency towards L-dopa production.

The current study focuses on the submerged fermentation of tyrosine hydroxylase (TH) from Aspergillus oryzae IIB-9 and its immobilization on zinc oxide nanocrystals (ZnO-NPs) for increased L-dopa production. The volume of Vogel's medium (75 ml), period of incubation (72 h), initial pH (5.5), and size of inoculum (1.5 ml) were optimal for maximum TH activity. The watch glass-dried (WG) and filter paper-dried (FP) ZnO-NPs were prepared and characterized using analytical techniques. The UV-Vis spectra revealed 295 and 285 nm absorption peaks for WG-ZnO-NPs and FP-ZnO-NPs dispersed in isopropanol. X-ray diffraction analysis confirmed the crystalline nature of ZnO-NPs. FTIR spectra band from 740 to 648.1/cm and 735.8/cm to 650.1/cm showed the stretching vibrations of WG-ZnO-NPs and FP-ZnO-NPs, respectively. The particle size of ZnO-NPs observed by scanning electron microscopy (SEM) images was between 130 and 170 nm. Furthermore, the stability of immobilized TH on ZnO-NPs was determined by varying the incubation period (10 min for WG-NPs and 15 min for FP-NPs) and temperature (45 °C and 30 °C for WG and FP-NPs, respectively). Incubating enzymes with various copper, iron, manganese, and zinc salts studied the catalytic efficiency of TH. Immobilization of TH on ZnO-NPs resulted in an 11.05-fold increase in TH activity, thus enhancing stability and catalytic efficiency.

Characterization and gastroprotective effects of Rosa brunonii Lindl. fruit on gastric mucosal injury in experimental rats - A preliminary study.

Gastric ulcer is the most prevalent disorder affecting a large population. Rosa brunonii Lindl. fruit (RBF) has traditionally been used to treat stomach pains. Therefore, the current work aimed to isolate, characterize, and investigate the gastro-protective effect of Rosa brunonii Lindl. fruit chloroform extract (RBFCE) against ethanol-induced gastric ulcers in rats. Quercetin 3-O-glucoside (QUE-G) was isolated and characterized by modern spectroscopic techniques. RBFCE was orally administered at 250 mg/kg, 500 mg/kg, and 750 mg/kg doses for ten days. Gastric ulcer was induced by a single dose of absolute ethanol (5 ml/kg) on the last day of the study. Histological changes were calculated, along with ulcer inhibition and the ulcer index (UI). Gastric juice volume, pH, acidity, mucus content, and protein content were evaluated to understand the mechanism underlying its gastroprotective effect. Omeprazole (OMP) was used as the positive control. RBFCE at a dose of 750 mg/kg significantly (p<0.01) reduced the UI (3.54) and increased the protection rate (67.63%) compared to the negative (ulcer) control group. Treatment with RBFCE in a dose-dependent manner increased the gastric pH, mucus content, and total protein while decreasing gastric juice volume and total acidity. Histopathological studies showed severe gastric mucosal injury and edema in ulcer control animals compared to extract-treated groups. This study demonstrated that oral administration of RBFCE possesses a significant gastroprotective effect due to its anti-secretory and cytoprotective mechanisms. Our findings support the traditional use of RBF to treat the gastric ulcer.

Phytochemical Constituents and In vitro Pharmacological Response of Cnidium monnieri; A Natural Ancient Medicinal Herb.

Background: Natural medicines are being used for the treatment of various disorders due to pharmacological, therapeutical, and nutraceuticals characteristics. Objectives: Current research was planned to explore In vitro pharmacological response of phytochemical constituents extracted from C. monnieri' seeds using aqueous ethanol (70%). Methods: Qualitative and quantitative measurements for phytochemical constituents were performed following reference protocols. Then In vitro antioxidant potential, cytotoxic studies, antimicrobial, and spermicidal pharmacological response of C. monnieri extract were investigated. Results: The results of High Performance Liquid Chromatography (HPLC), Fourier Transform Infra-Red (FTIR) spectroscopy, and Atomic Absorption Spectrophotometer (AAS) explored the presence of wide range of bioactive compounds with significant (p<.05) antioxidant activities. Cytotoxic studies revealed significant (p<.05) protective behavior of C. monnieri evaluated using CtDNA damage protection, against Salmonella typhi TA98 and TA100, RBCs membrane stabilizing and clot lysis assay. It was also found that selected herb has antibacterial and antifungal activities. The results of spermicidal study on human (n = 30) spermatozoa revealed significant (p<.05) contraceptive per vaginal behavior of this natural medicinal plant. Conclusion: It could be concluded that C. monnieri showed significant pharmacological activities with non-toxic behavior, however In vivo study in animals and clinical trials are required to declare this natural herb as therapeutic agent.

Nano-remediation technologies for the sustainable mitigation of persistent organic pollutants.

The absence of novel and efficient methods for the elimination of persistent organic pollutants (POPs) from the environment is a serious concern in the society. The pollutants release into the atmosphere by means of industrialization and urbanization is a massive global hazard. Although, the eco-toxicity associated with nanotechnology is still being debated, nano-remediation is a potentially developing tool for dealing with contamination of the environment, particularly POPs. Nano-remediation is a novel strategy to the safe and long-term removal of POPs. This detailed review article presents an important perspective on latest innovations and future views of nano-remediation methods used for environmental decontamination, like nano-photocatalysis and nanosensing. Different kinds of nanomaterials including nanoscale zero-valent iron (nZVI), carbon nanotubes (CNTs), magnetic and metallic nanoparticles, silica (SiO2) nanoparticles, graphene oxide, covalent organic frameworks (COFs), and metal organic frameworks (MOFs) have been summarized for the mitigation of POPs. Furthermore, the long-term viability of nano-remediation strategies for dealing with legacy contamination was considered, with a particular emphasis on environmental and health implications. The assessment goes on to discuss the environmental consequences of nanotechnology and offers consensual recommendations on how to employ nanotechnology for a greater present and a more prosperous future.

Prospects of microbial polysaccharides-based hybrid constructs for biomimicking applications.

Polysaccharides are biobased polymers obtained from renewable sources. They exhibit various interesting features including biocompatibility, biodegradability, and nontoxicity. Microbial polysaccharides are produced by several microorganisms including yeast, fungi, algae, and bacteria. Microbial polysaccharides have gained high importance in biotechnology due to their novel physiochemical characteristics and composition. Among microbial polysaccharides, xanthan, alginate, gellan, and dextran are the most commonly reported polysaccharides for the development of biomimetic materials for biomedical applications including targeted drug delivery, wound healing, and tissue engineering. Several chemical and physical cross-linking reactions are performed to increase their technological and functional properties. Owning to the broad-scale applications of microbial polysaccharides, this review aims to summarize the characteristics with different ways of physical/chemical crosslinking for polysaccharide regulation. Recently, several biopolymers have gained high importance due to their biologically active properties. This will help in the formation of bioactive nutraceuticals and functional foods. This review provides a perspective on microbial polysaccharides, with special emphasis given to applications in promising biosectors and the subsequent advancement on the discovery and development of new polysaccharides for adding new products.

Dopamine in Parkinson's disease.

Parkinson's disease is a neurodegenerative disease caused by the death of neurons, ie, cells critical to the production of dopamine, an important neurotransmitter in the brain. Here, we present a brief review of the dopamine synthetic pathway, binding to the dopamine receptors, and subsequent action. The production of dopamine (a monoamine neurotransmitter) occurs in the ventral tegmental area (VTA) of the substantia nigra, specifically in the hypothalamic nucleus and midbrain. Compared to other monoamines, dopamine is widely distributed in the olfactory bulb, midbrain substantia nigra, hypothalamus, VTA, retina, and the periaqueductal gray area. Dopamine receptors are large G-protein coupled receptor family members, of which there are five subtypes including D1, D2, D3, D4, and D5. These subtypes are further divided into two subclasses: D1-like family receptors (types 1 and 5) and D2-like family receptors (types 2, 3, and 4). Four different pathways and functions of the dopaminergic system are presented in this review. In the oxidation of dopamine, 5,6-indolequinone, dopamine-o-quinone, and aminochrome are formed. It is difficult to separate the roles of 5,6-indolequinone and dopamine-o-quinone in the degenerative process of Parkinson's diseases due to their instability. The role of aminochrome in Parkinson's disease is to form and stabilize the neurotoxic protofibrils of alpha-synuclein, mitochondrial dysfunction, oxidative stress, and the degradation of protein by lysosomal systems and proteasomes. The neurotoxic effects of aminochrome can be inhibited by preventing the polymerization of 5,6-indolequinone, dopamine-o-quinone, and aminochrome into neuromelanin, by reducing aminochrome catalysis by DT-diaphorase, and by preventing dopamine oxidative deamination catalyzed by monoamine oxidase. In addition to these, the conversion of dopamine in the neuromelanin (NM) shows both protective and toxic roles. Therefore, the aims of this review were to discuss and explain the role of dopamine and explore its physiology and specificity in Parkinson's disease, as well as its role in other physiological functions.

Physiopathology and effectiveness of therapeutic vaccines against human papillomavirus.

Human papillomavirus (HPV) is a well-known sexually transmitted disorder globally. Human papillomavirus (HPV) is the 3rd most common cancer that causes cervical carcinoma, and globally it accounts for 275,000 deaths every year. The load of HPV-associated abrasions can be lessened through vaccination. At present, three forms of prophylactic vaccines, Cervarix, Gadrasil, and Gardasil 9, are commercially accessible but all these prophylactic vaccines have not the ability to manage and control developed abrasions or infections. Therefore, a considerable amount of the population is not secured from HPV infectivity. Consequently, the development of therapeutic HPV vaccines is a crucial requirement of this era, for the treatment of persisting infections, and to stop the progression of HPV-associated cancers. Therapeutic vaccines are a developing trial approach. Because of the constitutive expression of E6 and E7 early genes in cancerous and pre-cancerous tissues, and their involvement in disturbance of the cell cycle, these are best targets for this therapeutic vaccine treatment. For the synthesis and development of therapeutic vaccines, various approaches have been examined comprising cell-based vaccines, peptide/protein-based vaccines, nucleic acid-based vaccines, and live-vector vaccines all proceeding towards clinical trials. This review emphasizes the development, progress, current status, and future perspective of several vaccines for the cure of HPV-related abrasions and cancers. This review also provides an insight to assess the effectiveness, safety, efficacy, and immunogenicity of therapeutic vaccines in the cure of patients infected with HPV-associated cervical cancer.

Hantavirus diseases pathophysiology, their diagnostic strategies and therapeutic approaches: A review.

Hantaviruses are enveloped negative (-) single-stranded RNA viruses belongs to Hantaviridae family, hosted by small rodents and entering into the human body through inhalation, causing haemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) also known as hantavirus cardiopulmonary syndrome (HCPS). Hantaviruses infect approximately more than 200 000 people annually all around the world and its mortality rate is about 35%-40%. Hantaviruses play significant role in affecting the target cells as these inhibit the apoptotic factor in these cells. These viruses impair the integrity of endothelial barrier due to an excessive innate immune response that is proposed to be central in the pathogenesis and is a hallmark of hantavirus disease. A wide range of different diagnostic tools including polymerase chain reaction (PCR), focus reduction neutralization test (FRNT), enzyme-linked immunosorbent assay (ELISA), immunoblot assay (IBA), immunofluorescence assay (IFA), and other molecular techniques are used as detection tools for hantavirus in the human body. Now the availability of therapeutic modalities is the major challenge to control this deadly virus because still no FDA approved drug or vaccine is available. Antiviral agents, DNA-based vaccines, polyclonal and monoclonal antibodies neutralized the viruses so these techniques are considered as the hope for the treatment of hantavirus disease. This review has been compiled to provide a comprehensive overview of hantaviruses disease, its pathophysiology, diagnostic tools and the treatment approaches to control the hantavirus infection.

REVIEW - Advancements in combination therapy of Hepatitis C virus.

Hepatitis C virus (HCV) is a primary cause of chronic liver disease along with various complications like liver cirrhosis and malignancy which leads to death. It has infected more than 185 million people worldwide. There is no congruence established for the treatment of various genotypes of HCV infection owing to diversity in prevalence globally. Assessment of affected individuals with HCV by polymerase chain reaction (PCR), viral load of HCV and liver enzyme levels (i.e., ALT and AST) are the foundation to evaluate the safety and efficacy of HCV therapies. The antiviral efficacy has been greatly improved and sustained viral response (SVR) rates increased from 6% with interferon monotherapy to 50-80% with PEG-interferon/ribavirin combination therapy to >95% after the approval of all interferon free oral direct acting antiviral agents. The main objective of this review article is to compile data from reference sources regarding the old and current therapeutic strategies used to manage HCV infection. It is accepted that chronic HCV infection increases patient's thrombocytopenia and neutropenia risk and complications increased in co-morbid disorders like in tuberculosis, HIV, diabetes etc. In past treatment associated side effects were the major consequences and many patients have to stop the treatment. But after the approval of direct acting antiviral drugs create a revolution in the treatment of HCV infection. So, it could be concluded that current combination therapies are a promising hope to eradicate and to control HCV but some safety concerns required more considerations Therefore, this review focus on the available latest combination therapies and their effectiveness to eradicate HCV infection.

Naegleria fowleri: Sources of infection, pathophysiology, diagnosis, and management; a review.

Naegleria fowleri, a thermophilic flagellate amoeba known as a "brain-eating" amoeba, is the aetiological agent of a perilous and devastating waterborne disease known as primary amoebic meningoencephalitis (PAM), both in humans as well as in animals. PAM is a rare but fatal disease affecting young adults all around the world, particularly in the developed world but recently reported from developing countries, with 95%-99% mortality rate. Swimmers and divers are at high risk of PAM as the warm water is the most propitious environment adapted by N. fowleri to cause this infection. Infective amoeba in the trophozoite phase enter the victim's body through the nose, crossing the cribriform plate to reach the human brain and cause severe destruction of the central nervous system (CNS). The brain damage leads to brain haemorrhage and death occurs within 3-7 days in undiagnosed cases and maltreated cases. Though the exact pathogenesis of N. fowleri is still not known, it has exhibited two primary mechanisms, contact-independent (brain damage through different proteins) and contact-dependent (brain damage through surface structures food cups), that predominantly contribute to the pathogen invading the host CNS. For the management of this life-threatening infection different treatment regimens have been applied but still the survival rate is only 5% which is ascribed to its misdiagnosis, as the PAM symptoms closely resembled bacterial meningitis. The main objectives of this review article are to compile data to explore the sources and routes of N. fowleri infection, its association in causing PAM along with its pathophysiology; latest techniques used for accurate diagnosis, management options along with challenges for Pakistan to control this drastic disorder.