Unravelling the therapeutic potential of forkhead box proteins in breast cancer: An update (Review).

Breast cancer, a prominent cause of mortality among women, develops from abnormal growth of breast tissue, thereby rendering it one of the most commonly detected cancers in the female population. Although numerous treatment strategies are available for breast cancer, discordance in terms of effective treatment and response still exists. Recently, the potential of signaling pathways and transcription factors has gained substantial attention in the cancer community; therefore, understanding their role will assist researchers in comprehending the onset and advancement of breast cancer. Forkhead box (FOX) proteins, which are important transcription factors, are considered crucial regulators of various cellular activities, including cell division and proliferation. The present study explored several subclasses of FOX proteins and their possible role in breast carcinogenesis, followed by the interaction between microRNA (miRNA) and FOX proteins. This interaction is implicated in promoting cell infiltration into surrounding tissues, ultimately leading to metastasis. The various roles that FOX proteins play in breast cancer development, their intricate relationships with miRNA, and their involvement in therapeutic resistance highlight the complexity of breast cancer dynamics. Therefore, recognizing the progress and challenges in current treatments is crucial because, despite advancements, persistent disparities in treatment effectiveness underscore the need for ongoing research, with future studies emphasizing the necessity for targeted strategies that account for the multifaceted aspects of breast cancer.

Cytotoxic potential and metabolomic profiling of alkaloid rich fraction of Tylophora indica leaves.

Tylophora indica (Burm f.) Merrill, belong to family Asclepiadaceae, is considered to be a natural remedy with high medicinal benefits. The objective of this work is to assess the metabolomic profile of T. indica leaves enriched in alkaloids, as well as to evaluate the in vitro cytotoxicity of these leaves using the MTT assay on human breast MCF-7 and liver HepG2 cancer cell lines. Dried leaves of T. indica were extracted by sonication, using methanol containing 2 % (v/v) of acetic acid and obtained fraction was characterized by HPTLC and UPLC-MS. The UPLC-MS study yielded a preliminary identification of 32 metabolites, with tylophorine, tylophorine B, tylophorinine, and tylophorinidine being the predominant metabolites. The cytotoxicity of the extract of T. indica was evaluated on HepG2 and MCF-7 cell lines, yielding inhibitory concentration (IC50) values of 75.71 µg/mL and 69.60 µg/mL, respectively. Data suggested that the phytochemical screening clearly showed presence of numerous secondary metabolites with moderate cytotoxic efficacy. In conclusion, the future prospects of T. indica appear promising for the advancement of phytopharmaceutical-based anticancer medications, as well as for the design of contemporary pharmaceuticals in the field of cancer chemotherapy.

The role of Aedes aegypti in inducing/aggravating IgE-mediated allergic airway disease: extensive computational studies for identification of allergenic proteins.

Respiratory allergies have become a major public health concern and affect one-third of the world's population. Several factors like environmental changes, industrialization, and immunologic interactions are reported to contribute to allergic respiratory diseases. Immunological reactions because of mosquito bite (allergic proteins) have been reported to have a high contribution to IgE-mediated allergic airway disease but they are largely ignored. In this study, we aim to predict the potential allergens (proteins) from Aedes aegypti that might play a role in the reactions of IgE-mediated allergic airway diseases. The allergens are identified from an extensive literature search and the 3D structures were prepared using the SwissDock server. Computational studies were performed to identify the potential allergens that might be responsible for IgE-mediated allergies. Our docking and molecular dynamics (MD) simulation results suggest that ADE-3, an allergen from Aedes aegypti, has the highest docking score and is predicted to be responsible for IgE-mediated allergic reaction(s). Overall, this study highlights the importance of immunoinformatics, and the obtained information can be used for designing prophylactic peptide vaccine candidates and inhibitors for controlling IgE-mediated inflammations.Communicated by Ramaswamy H. Sarma.

Potential honey bee (Apis mellifera) allergens associated with IgE-mediated allergy- An In-silico study.

Allergies due to honeybee venom (HBV) are reported to be the second most common form of allergy to Hymenoptera venom that occurs after being stung. Indeed, 15-20% of people test IgE positive after being stung. However, accurate data on the incidence of honey bee allergens is missing and estimated to be less than 0.001%. Beekeeping is an ancient and widely practiced activity across the Kingdom of Saudi Arabia. Still, studies on the allergenic effect of the different subspecies of honey bees are very rare in Saudi Arabia. Hence, in this study, using the In-silico approach, we aimed to study and evaluate the effect of allergens from honey bees in Ha'il City, Saudi Arabia on IgE-mediated allergies. A list of potential allergens from Apis mellifera was prepared, and the 3D structure was prepared using the SWISS-MODEL web server and the PDB database was used for retrieving the structure of the immunoglobulin E- fragment antigen-binding (IgE-Fab) region. Molecular docking (clusPro webserver) and molecular dynamics (Schrödinger) results revealed that the B2D0J5 protein from Apis mellifera might be the key protein associated with IgE-mediated allergic response. Overall, the identified knowledge can be used for exploring prophylactic vaccine candidates and improving the diagnosis of allergic reactions to honey bees in the Ha'il region of Saudi Arabia.

Journey of CAR T­cells: Emphasising the concepts and advancements in breast cancer (Review).

Cancer is the primary and one of the most prominent causes of the rising global mortality rate, accounting for nearly 10 million deaths annually. Specific methods have been devised to cure cancerous tumours. Effective therapeutic approaches must be developed, both at the cellular and genetic level. Immunotherapy offers promising results by providing sustained remission to patients with refractory malignancies. Genetically modified T­lymphocytic cells have emerged as a novel therapeutic approach for the treatment of solid tumours, haematological malignancies, and relapsed/refractory B­lymphocyte malignancies as a result of recent clinical trial findings; the treatment is referred to as chimeric antigen receptor T­cell therapy (CAR T­cell therapy). Leukapheresis is used to remove T­lymphocytes from the leukocytes, and CARs are created through genetic engineering. Without the aid of a major histocompatibility complex, these genetically modified receptors lyse malignant tissues by interacting directly with the carcinogen. Additionally, the outcomes of preclinical and clinical studies reveal that CAR T­cell therapy has proven to be a potential therapeutic contender against metastatic breast cancer (BCa), triple­negative, and HER 2+ve BCa. Nevertheless, unique toxicities, including (cytokine release syndrome, on/off­target tumour recognition, neurotoxicities, anaphylaxis, antigen escape in BCa, and the immunosuppressive tumour microenvironment in solid tumours, negatively impact the mechanism of action of these receptors. In this review, the potential of CAR T­cell immunotherapy and its method of destroying tumour cells is explored using data from preclinical and clinical trials, as well as providing an update on the approaches used to reduce toxicities, which may improve or broaden the effectiveness of the therapies used in BCa.

A comprehensive immunoinformatics study to explore and characterize potential vaccine constructs against Ole e 9 allergen of Olea europaea.

Immunoglobulin E (IgE)-mediated allergy, which affects more than 30% of the population, is the most prevalent hypersensitivity illness. In an atopic individual, even a small amount of allergen exposure can cause IgE antibodies to be produced. Due to the engagement of receptors that are highly selective for IgE, even tiny amounts of allergens can induce massive inflammation. This study focuses on the exploration and characterization of the allergen potential of Olea europaea allergen (Ole e 9) affecting the population in Saudi Arabia. A systematic computational approach was performed to identify potential epitopes of allergens and complementary determining regions of IgE. In support, physiochemical characterization and secondary structure analysis unravel the structural conformations of allergens and active sites. Epitope prediction uses a pool of computational algorithms to identify plausible epitopes. Furthermore, the vaccine construct was assessed for its binding efficiency using molecular docking and molecular dynamics simulation studies, which led to strong and stable interactions. This is because IgE is known to play a role in allergic responses, which facilitate host cell activation for an immune response. Overall, the immunoinformatics analysis advocates that the proposed vaccine candidate is safe and immunogenic and therefore can be pushed as a lead for in vitro and in vivo investigations.Communicated by Ramaswamy H. Sarma.

In Silico Comparative Exploration of Allergens of Periplaneta americana, Blattella germanica and Phoenix dactylifera for the Diagnosis of Patients Suffering from IgE-Mediated Allergic Respiratory Diseases.

The burden of allergic illnesses is continuously rising, and patient diagnosis is a significant problem because of how intricately hereditary and environmental variables interact. The past three to four decades have seen an outbreak of allergies in high-income countries. According to reports on the illness, asthma affects around 300 million individuals worldwide. Identifying clinically important allergens for the accurate classification of IgE-mediated allergy respiratory disease diagnosis would be beneficial for implementing standardized allergen-associated therapy. Therefore, the current study includes an in silico analysis to identify potential IgE-mediated allergens in date palms and cockroaches. Such an immunoinformatic approach aids the prioritization of allergens with probable involvement in IgE-mediated allergic respiratory diseases. Immunoglobulin E (IgE) was used for molecular dynamic simulations, antigen-antibody docking analyses, epitope identifications, and characterizations. The potential of these allergens (Per a7, Per a 1.0102, and Bla g 1.0101) in IgE-mediated allergic respiratory diseases was explored through the evaluation of physicochemical characteristics, interaction observations, docking, and molecular dynamics simulations for drug and vaccine development.

MD Simulation Studies for Selective Phytochemicals as Potential Inhibitors against Major Biological Targets of Diabetic Nephropathy.

Diabetes is emerging as an epidemic and is becoming a public health concern worldwide. Diabetic nephropathy is one of the serious complications of diabetes, and about 40% of individuals with diabetes develop diabetic nephropathy. The consistent feature of diabetes and its associated nephropathy is hyperglycemia, and in some cases, hyperamylinemia. Currently, the treatment includes the use of medication for blood pressure control, sugar control, and cholesterol control, and in the later stage requires dialysis and kidney transplantation, making the management of this complication very difficult. Bioactive compounds, herbal medicines, and extracts are extensively used in the treatment and prevention of several diseases, and some are reported to be efficacious in diabetes too. Therefore, in this study, we tried to identify the therapeutic potential of phytochemicals used in in silico docking and molecular dynamic simulation studies using a library of 5284 phytochemicals against the two potential targets of type 2 diabetes-associated nephropathy. We identified two phytochemicals (i.e., gentisic acid and michelalbine) that target human amylin peptide and dipeptidyl peptidase-4, respectively, with good binding affinity. These phytochemicals can be further evaluated using in vitro and in vivo studies for their anti-hyperglycemia and anti-hyperamylinemia effects.

Identifying the alpha-glucosidase inhibitory potential of dietary phytochemicals against diabetes mellitus type 2 via molecular interactions and dynamics simulation.

The research aims to identify the inhibitory potential of natural dietary phytochemicals against non-insulinotropic target protein alpha-glucosidase and its possible implications to diabetes mellitus type 2. A data set of sixteen plant-derived dietary molecules viz., 4,5-dimethyl-3-hydroxy-2(5H)-furanone, apigenin, bromelain, caffeic acid, cholecalciferol, dihydrokaempferol 7-o-glucopyranoside, galactomannan, genkwanin, isoimperatorin, luteolin, luteolin 7-o-glucoside, neohesperidin, oleanoic acid, pelargonidin-3-rutinoside, quercetin, and quinic acid were taken to accomplish molecular docking succeeded by their comparison with known inhibitors including acarbose, miglitol, voglibose, emiglitate, and 1-deoxynojirimycin. Among all phyto-compounds, bromelain (ΔG: -9.54 kcal/mol), cholecalciferol (-8.47 kcal/mol), luteolin (-9.02 kcal/mol), and neohesperidin (-8.53 kcal/mol) demonstrated better binding interactions with alpha-glucosidase in comparison to the best-known inhibitor, acarbose (ΔG: -7.93 kcal/mol). Molecular dynamics simulation of 10 ns duration, CYP450 site of metabolism identification, and prediction of activity spectra for substances depicted the bromelain as the most stable inhibitor compared to luteolin and acarbose. Findings of molecular interactions, molecular dynamics study, metabolism, and biological activity prediction proved bromelain as a potential alpha-glucosidase inhibitor. Thus, bromelain might be helpful as an insulin-independent therapeutic molecule towards controlling and managing diabetes mellitus type 2.

Nephroprotective effects of polyherbal extract via attenuation of the severity of kidney dysfunction and oxidative damage in the diabetic experimental model.

In view of many complications of diabetes, kidney failure is considered as one of the main complications. The oxidative stress-induced due to persistent hyperglycemic conditions is the major cause of kidney disease. The present study was designed to explore the nephroprotective efficacy of polyherbal (PH) extract in a diabetic model induced by streptozotocin (STZ). STZ (55 mg/kg body weight, intraperitoneal) was injected in overnight fasting rats to develop the diabetic experimental model. Effect on kidney injury was evaluated by investigating biochemical and histological evidences in renal tissue after 56 days of treatment of PH extract. Results showed the high glucose level in STZ treated rats that suggested hyperglycemia persistence along with the successful establishment of nephropathy in diabetic rats with altered renal function, inflammatory cytokines level as well as oxidative and nitrosative stress. Administration of PH extract significantly improved the glycemic condition, glomerular function and proximal reabsorptive markers. Further, elevated pro-inflammatory cytokines levels and disturbed redox status were restored. Moreover, findings were fostered and substantiated by histopathological examinations. Our work strongly proposes that the nephroprotective effect of the PH extract on renal damage could be attributed due to its anti-inflammatory and antioxidant properties. Thus, PH extract could have potential as a pharmaceutical drug for diabetes mellitus (DM). Additional long-term study or clinical trial is required for further investigations.

miRNAs and the Hippo pathway in cancer: Exploring the therapeutic potential (Review).

Cancer is recognized as the leading cause of death worldwide. The hippo signaling pathway regulates organ size by balancing cell proliferation and cell death; hence dysregulation of the hippo pathway promotes cancer­like conditions. miRNAs are a type of non­coding RNA that have been shown to regulate gene expression. miRNA levels are altered in various classes of cancer. Researchers have also uncovered a crosslinking between miRNAs and the hippo pathway, which has been linked to cancer. The components of the hippo pathway regulate miRNA synthesis, and various miRNAs regulate the components of the hippo pathway both positively and negatively, which can lead to cancer­like conditions. In the present review article, the mechanism behind the hippo signaling pathway and miRNAs biogenesis and crosslinks between miRNAs and the hippo pathway, which result in cancer, shall be discussed. Furthermore, the article will cover miRNA­related therapeutics and provide an overview of the development of resistance to anticancer drugs. Understanding the underlying processes would improve the chances of developing effective cancer treatment therapies.

Prospects of microbial-engineering for the production of graphene and its derivatives: Application to design nanosystms for cancer theranostics.

Cancer is known as one of the leading causes of morbidity and fatality, currently faced by our society. The prevalence of cancer related dieses is rapidly increasing around the world. To reduce the mortality rates, early diagnosis and subsequent treatment of cancer in timely manner is quite essential. Advancements have been made to achieve effective theranostics strategies to tackle cancerous dieses, yet very challenging to overcome this issue. Recently, advances made in the field of nanotechnology have shown tremendous potential for cancer theranostics. Different types of nanomaterials have been successfully employed to develop sophisticated diagnosis and therapy techniques. In this context, graphene and its derivatives e.g. graphene oxide (GO) and reduced graphene oxide (RGO) have been investigated as promising candidates to design graphene-based nanosystems for the diagnosis and therapeutic purpose. Further, to synthesize graphene and its derivatives different types of physicochemical methods are being adopted. However, each method has its own advantage and disadvantages. In this reference, among diverse biological methods, microbial technique can be one of the most promising and eco-friendly approach for the preparation of graphene and its derivatives, particularly GO and RGO. In this review, we summarize studies performed on the preparation of graphene and its derivatives following microbial routes meanwhile focus has been made on the preparation method and the possible mechanism involved therein. Thereafter, we have discussed applications of graphene and its derivatives to developed advanced nanosystem that can be imperative for the cancer theranostics. Results of recent studies exploring applications graphene based nanosystem for the preparation of different types of biosensors for early diagnosis; advanced therapeutic approaches by designing drug delivery nanosystems along with multifunctionality (e.g cancer imaging, drug delivery, photodynamic and photo thermal therapy) in cancer theranostics have been discussed. Particularly, emphasis has been given on the preparation techniques of graphene based nanosystems, being employed in designing of biosensing platforms, drug delivery and multifunctional nanosystems. Moreover, issues have been discussed on the preparation of graphene and its derivatives following microbial technique and the implementation of graphene based nanosystems in cancer theranostics.

Psychological impact and stress factors among Ha'il medical students post COVID19 pandemic.

The current COVID-19 pandemic frightfully threatened the whole world, and people in different countries were demanded to be quarantined due to possible contact with the infection. High mortality rate, the spread of COVID19 and the propagation of fake news in social media programs created fear and anxiety among majority of society especially, medical students. One of the most essential changes during the covid-19 was the termination of teaching lectures in physical presence and its replacement by virtual online lectures. Circumstances like these have negative impact on the mental health of medical students. Therefore, it is of interest to investigate the impact of the COVID19 pandemic on medical students' learning and the effect of distressing situation they experienced, psychological and educational variables specifically during return to physical attendance in college and the impact of these variables of probably affecting factors like age, gender, marital status, transition of preclinical years to clinical years. A Cross-sectional study was completed among medical students at UOH, KSA. The data are collected by distributing an online questionnaire. Statistical analysis has been done with Microsoft Power BI. 14.82% of 5th year female participants were unable to stop worrying for different things while 10.54% of male participant were in the 1st year. Large numbers of students who have increased the number of times they wash their hands are found in med3 and med4 while 27.92% agree and 29.05% strongly agree of whole years of study. 45.29% of students were having mental pressure before online session due to internet connection while 51.55% had decreased motivation since the shift to online learning. Data shows that highest numbers of participants who were having past illness and anxious were in age group 21-23 in both male and female. The majority of students was having fear toward returning in physical presence and preferred not to have on- college education. Hence, it is recommended to encourage students and reduce stress by providing with Personal Protective Equipment (PPE) course.

Assessment of bio-contaminants during COVID-19 outbreak from the indoor environment of Hail city, Kingdom of Saudi Arabia.

Biocontaminants are minute particles derived from different biological materials. Indoor biocontaminants are associated with major public health problems. In Gulf countries, it is more precarious due to the harsh climatic conditions, including high ambient temperatures and relative humidity. In addition, due to COVID-19 pandemic, most of the time public is inside their home. Therefore, the aim of the study was to determine the load of biocontaminants in the indoor environment of Hail city. The results showed that most of the bacteria are gram-positive and higher in polymicrobial (87.1%) than monomicrobial (62.7%) association. There was no significant association with sample collection time and types of isolates. The most abundant microbes found in all samples were Staphylococcus aureus followed by Bacillus spp. Among Gram-negative bacterial isolates, E. coli was most common in tested indoor air samples. The study will be useful to find the biocontaminants associated with risk factors and their impact on human health in indoor environment, especially during the COVID-19 pandemic. These results indicate the need to implement health care awareness programs in the region to improve indoor air quality.

IN VITRO ANTHELMINTIC EFFICACY OF NATIVE PLANTS AGAINST HAEMONCHUS CONTORTUS.

The current study aimed to investigate in vitro anthelmintic efficacy of two medicinally important plants against Haemonchus contortus in small ruminants. Fruit peel of Punica granatum Linn. (vern. Anar), leaves and roots of Berberis lycium Royle (vern. Sumbal) were tested for their anthelmintic efficacy. Methanolic extracts of the test plants from various plant parts were tested for anthelmintic efficacy against the Haemonchus contortous using albendazole as a reference standard. The results revealed that both the plant extracts exhibited potent anthelmintic activity at concentrations higher than 50 mg/mL when tested against their respective standard drug. In case of Berberis lycium Royle when the results were compared, methanolic roots extracts showed more potent activity as compared to leaves extracts at the same concentration. It was observed that the in vitro anthelmintic potential of Punica granatum Linn. fruit peel and Berberis lyceium Royale root can be used to treat helminth infections after in vivo trails.