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BackgroundColorectal cancer (CRC) ranks among the top three cancers globally in both incidence and mortality, posing a significant public health challenge. Most CRC cases are diagnosed at intermediate to advanced stages, and reliable biomarkers for early detection are lacking. Long non-coding RNAs (lncRNAs) have been implicated in various cancers, including CRC, playing key roles in tumor development, progression, and prognosis.MethodsA comprehensive search of the PubMed database was conducted to identify relevant studies on the early diagnosis of CRC. Bioinformatics analysis was performed to explore lncRNA-mRNA networks, leading to the identification of five potential blood biomarkers. Expression analysis was carried out using the GEPIA and GEO online databases, focusing on MYC and STAT3. Differential expression between normal and CRC tissues was assessed, followed by Receiver Operating Characteristic (ROC) analysis to evaluate the diagnostic potential of these markers. Quantitative Real-Time PCR (qRT-PCR) was performed to validate MYC and STAT3 expression levels, and findings were further confirmed using the Human Protein Atlas (HPA) database.ResultsDatabase analysis revealed significant differential expression of MYC and STAT3 between normal and CRC tissues. ROC analysis demonstrated the diagnostic potential of these markers. qRT-PCR validation confirmed the differential expression patterns observed in the databases. Validation through the HPA database further supported these findings, confirming the potential of MYC and STAT3 as diagnostic biomarkers for CRC.ConclusionOur results suggest that MYC and STAT3 are promising diagnostic biomarkers for CRC, offering new insights into its pathophysiology and potential for targeted therapies.

Abstract Diabetic retinopathy (DR) is an eye disease that causes blindness and vision loss in diabetic. Risk factors for DR include high blood glucose levels and some environmental factors. The pathogenesis is based on inflammation caused by interferon and other nuclear proteins. This review article provides an overview of DR and discusses the role of nuclear proteins in the pathogenesis of the disease. Some core proteins such as MAPK, transcription co-factors, transcription co-activators, and others are part of this review. In addition, some current advanced treatment resulting from the role of nuclear proteins will be analyzes, including epigenetic modifications, the use of methylation, acetylation, and histone modifications. Stem cell technology and the use of nanobiotechnology are proposed as promising approaches for a more effective treatment of DR.

Abstract In the past, hydrogen sulfide (H2S) was recognized as a toxic and dangerous gas; in recent years, with increased research, we have discovered that H2S can act as an endogenous regulatory transmitter. In mammals, H2S‐catalyzing enzymes, such as cystathionine‐β‐synthase, cystathionine‐γ‐lyase, and 3‐mercaptopyruvate sulfurtransferase, are differentially expressed in a variety of tissues and affect a variety of biological functions, such as transcriptional and posttranslational modification of genes, activation of signaling pathways in the cell, and metabolic processes in tissues, by producing H2S. Various preclinical studies have shown that H2S affects physiological and pathological processes in the body. However, a detailed systematic summary of these roles in health and disease is lacking. Therefore, this review provides a thorough overview of the physiological roles of H2S in different systems and the diseases associated with disorders of H2S metabolism, such as ischemia–reperfusion injury, hypertension, neurodegenerative diseases, inflammatory bowel disease, and cancer. Meanwhile, this paper also introduces H2S donors and novel release modes, as well as the latest preclinical experimental results, aiming to provide researchers with new ideas to discover new diagnostic targets and therapeutic options.

Abstract For a long time, hydrogen sulfide (H2S) has been considered a toxic compound, but recent studies have found that H2S is the third gaseous signaling molecule which plays a vital role in physiological and pathological conditions. Currently, a large number of studies have shown that H2S mediates apoptosis through multiple signaling pathways to participate in cancer occurrence and development, for example, PI3K/Akt/mTOR and MAPK signaling pathways. Therefore, the regulation of the production and metabolism of H2S to mediate the apoptotic process of cancer cells may improve the effectiveness of cancer treatment. In this review, the role and mechanism of H2S in cancer cell apoptosis in mammals are summarized.

Autophagy is an evolutionarily conserved cellular recycling process that maintains cellular homeostasis. Despite extensive research in endocrine contexts, the role of autophagy in ovarian and testicular steroidogenesis remains elusive. The significant role of autophagy in testosterone production suggests potential treatments for conditions like oligospermia and azoospermia. Further, influence of autophagy in folliculogenesis, ovulation, and luteal development emphasizes its importance for improved fertility and reproductive health. Thus, investigating autophagy in gonadal cells is clinically significant. Understanding these processes could transform treatments for endocrine disorders, enhancing reproductive health and longevity. Herein, we provide the functional role of autophagy in testicular and ovarian steroidogenesis to date, highlighting its modulation in testicular steroidogenesis and its impact on hormone synthesis, follicle development, and fertility therapies.

Hydrogen sulfide (H2S) is one of the three known gas signal transducers, and since its potential physiological role was reported, the literature on H2S has been increasing. H2S is involved in processes such as vasodilation, neurotransmission, angiogenesis, inflammation, and the prevention of ischemia-reperfusion injury, and its mechanism remains to be further studied. At present, the role of post-translational processing of proteins has been considered as a possible mechanism for the involvement of H2S in a variety of physiological processes. Current studies have shown that H2S is involved in S-sulfhydration, phosphorylation, and S-nitrosylation of proteins, etc. This paper focuses on the effects of protein modification involving H2S on physiological and pathological processes, looking forward to providing guidance for subsequent research.

Background: Hydrogen sulfide (H2S) has been identified as the third gaseous signaling molecule. Endogenous H2S plays a key role in the progression of various types of cancer. However, the effect of endogenous H2S on the growth of esophageal cancer (EC) remains unknown. Methods: In this study, three kinds of H2S-producing enzymes inhibitors, DL-propargylglycine (PAG, inhibitor of cystathionine-γ-lyase), aminooxyacetic acid (AOAA, inhibitor of cystathionine-β-synthase), and L-aspartic acid (L-Asp, inhibitor of 3-mercaptopyruvate sulfurtransferase) were used to determine the role of endogenous H2S in the growth of EC9706 and K450 human EC cells. Results: The results indicated that the combination (PAG+AOAA+L-Asp) group showed higher inhibitory effects on the viability, proliferation, migration, and invasion of EC cells than PAG, AOAA, and L-Asp group. Inhibition of endogenous H2S promoted apoptosis via activation of mitogen-activated protein kinase pathway in EC cells. Endogenous H2S suppression triggered pyroptosis of EC cells by activating reactive oxygen species-mediated nuclear factor-κB signaling pathway. In addition, the combine group showed its more powerful growth-inhibitory effect on the growth of human EC xenograft tumors in nude mice without obvious toxicity. Conclusion: Our results indicate that inhibition of endogenous H2S production can significantly inhibit human EC cell growth via promotion of apoptosis and pyroptosis. Endogenous H2S may be a promising therapeutic target in EC cells. Novel inhibitors for H2S-producing enzymes can be designed and developed for EC treatment.

Summary: Neurological diseases are one of the most pressing issues in modern times worldwide. It thus possesses explicit attention from researchers and medical health providers to guard public health against such an expanding threat. Various treatment modalities have been developed in a remarkably short time but, unfortunately, have yet to lead to the wished-for efficacy or the sought-after clinical improvement. The main hurdle in delivering therapeutics to the brain has always been the blood-brain barrier which still represents an elusive area with lots of mysteries yet to be solved. Meanwhile, nanotechnology has emerged as an optimistic platform that is potentially holding the answer to many of our questions on how to deliver drugs and treat CNS disorders using novel technologies rather than the unsatisfying conventional old methods. Nanocarriers can be engineered in a way that is capable of delivering a certain therapeutic cargo to a specific target tissue. Adding to this mind-blowing nanotechnology, the revolutionizing gene-altering biologics can have the best of both worlds, and pave the way for the long-awaited cure to many diseases, among those diseases thus far are Alzheimer’s disease (AD), brain tumors (glioma and glioblastoma), Down syndrome, stroke, and even cases with HIV. The review herein collects the studies that tested the mixture of both sciences, nanotechnology, and epigenetics, in the context of brain therapeutics using three main categories of gene-altering molecules (siRNA, miRNA, and CRISPR) with a special focus on the advancements regarding the new favorite, intranasal route of administration.

Monkeypox (Mpox) is a virus that first emerged in Africa in 1970 [...]

Background: Skin cancer has been the leading type of cancer worldwide. Melanoma and non-melanoma skin cancers are now the most common types of skin cancer that have been reached to epidemic proportion. Based on the rapid prevalence of skin cancers, and lack of efficient drug delivery systems, it is essential to surge the possible ways to prevent or cure the disease. Aim of review: Although surgical modalities and therapies have been made great progress in recent years, however, there is still an urgent need to alleviate its increased burden. Hence, understanding the precise pathophysiological signaling mechanisms and all other factors of such skin insults will be beneficial for the development of more efficient therapies. Key scientific concepts of review: In this review, we explained new understandings about onset and development of skin cancer and described its management via polymeric micro/nano carriers-based therapies, highlighting the current key bottlenecks and future prospective in this field. In therapeutic drug/gene delivery approaches, polymeric carriers-based system is the most promising strategy. This review discusses that how polymers have successfully been exploited for development of micro/nanosized systems for efficient delivery of anticancer genes and drugs overcoming all the barriers and limitations associated with available conventional therapies. In addition to drug/gene delivery, intelligent polymeric nanocarriers platforms have also been established for combination anticancer therapies including photodynamic and photothermal, and for theranostic applications. This portfolio of latest approaches could promote the blooming growth of research and their clinical availability.

The world is currently dealing with a second viral outbreak, monkeypox, which has the potential to become an epidemic after the COVID-19 pandemic. People who reside in or close to forest might be exposed indirectly or at a low level, resulting in subclinical disease. However, the disease has lately emerged in shipped African wild mice in the United States. Smallpox can cause similar signs and symptoms to monkeypox, such as malaise, fever, flu-like signs, headache, distinctive rash, and back pain. Because Smallpox has been eliminated, similar symptoms in a monkeypox endemic zone should be treated cautiously. Monkeypox is transmitted to humans primarily via interaction with diseased animals. Infection through inoculation via interaction with skin or scratches and mucosal lesions on the animals is conceivable significantly once the skin barrier is disrupted by scratches, bites, or other disturbances or trauma. Even though it is clinically unclear from other pox-like infections, laboratory diagnosis is essential. There is no approved treatment for human monkeypox virus infection, however, smallpox vaccination can defend counter to the disease. Human sensitivity to monkeypox virus infection has grown after mass vaccination was discontinued in the 1980s. Infection may be prevented by reducing interaction with sick patients or animals and reducing respiratory exposure among people who are infected.

Abstract Background Sphingosine-1-phosphate (S1P) is a bioactive metabolite of sphingolipids and produced by sphingosine kinases (SphK1 and SphK2). SphK1/S1P pathway is implicated in the progression of chronic kidney disease. However, the role of SphK1/S1P pathway in renal injury in hypertension has not been reported. This study tested the hypothesis that SphK1/S1P pathway mediates the kidney damage in DOCA-salt hypertensive mice. Methods Male wild type (WT) C57BL6 and SphK1 knockout (KO) mice were subjected to unilateral nephrectomy, subcutaneous implant containing 50 mg of deoxycorticosterone acetate (DOCA) and 1% NaCl drinking water for 7 weeks. At the end of experiments, blood pressure data, 24 h urine and kidney samples were collected. Renal mRNA levels of SphK1 were measured by real-time RT-PCR. Markers for fibrogenesis and immune cell infiltration in kidneys were detected using Western blot and immunohistochemistray analysis, respectively. The glomerular morphological changes were examined in kidney tissue slides stained with Periodic-Acid Schiff. Four groups were studied: wild type control (WT-C), WT-DOCA, KO-C and KO-DOCA. Results The renal SphK1 mRNA expression was significantly upregulated in WT-DOCA mice, whereas this upregulation of renal SphK1 mRNA was blocked in KO-DOCA mice. There was no difference in DOCA-salt-induced hypertension between WT and KO mice. The urinary albumin was increased in both DOCA-salt groups. However, the albuminuria was significantly lower in KO-DOCA than in WT-DOCA group. There were increases in glomerulosclerosis indices in both DOCA-salt groups, whereas the increases were also significantly lower in KO-DOCA than in WT-DOCA mice. Renal protein levels of α-smooth muscle actin were upregulated in both DOCA-salt groups, but the increase was significant lower in KO-DOCA than in WT-DOCA group. The increased staining areas of collagen detected by Sirius Red-staining in kidney tissue sections were also attenuated in KO-DOCA compared with WT-DOCA mice. In contrast, the increased infiltration of CD43+ (a T cell marker) or CD68+ (a macrophage marker) cells in DOCA-salt kidneys showed no significant difference between WT-DOCA and KO-DOCA mice. Conclusions SphK1/S1P signaling pathway mediates kidney damage in DOCA-salt hypertensive mice independent of blood pressure and immune modulation.

PEST-containing nuclear protein (PCNP), a novel nuclear protein, is involved in vital cellular processes like cell proliferation and mediates tumorigenesis. PCNP is a short-living, small nuclear protein of only 178 amino acids with two remarkable PEST sequences that are rich in proline (P), glutamic acid (E), serine (S), and threonine (T). The current understanding of PCNP reveals that PCNP has the ability to interact with cell cycle regulatory proteins; tumor suppressors (p53 and pRB), and promoters (cyclin E and cyclin D) to determine the fate of tissues to facilitate the process of either apoptosis or cell proliferation. In many preclinical studies, it has been evaluated that PCNP expression has associations with the development and progression of various cancers like neuroblastoma, lung adenocarcinoma, and ovarian cancer. Based on these depicted novel roles of PCNP in cell cycleregulation and of PCNP in tumorigenesis, it is logical to consider PCNP as a potential molecular target for cancer research. The aim of the current communication is to present an update on PCNP research and discussion on the potential role of PCNP in cancer development with challenges and opportunities perspectives. Considering the available evidence as a baseline for our statement, we anticipate that in the future, new research insights will strengthen the aim to develop PCNP-based diagnostic and therapeutic approaches that will move the PCNP from the laboratory to the cancer clinic.

Monkeypox virus is a double-stranded DNA virus species that causes disease in humans and mammals. It is a zoonotic virus belongs the genus Orthopoxviral, the family of Poxviridae, associated with the smallpox virus in many aspects. The first human case of monkeypox was reported throughout the Democratic Republic of Congo in 1970. In April 2022, several cases were recorded in widespread regions of Africa, the Northern and western hemispheres. The current review spotlights taxonomic classification, clinical presentations during infection, and the pathogenicity of the monkeypox virus in humans. Furthermore, the current review also highlights different diagnostics used for virus detection.

Monkeypox is a serious public health issue in tropical and subtropical areas. Antivirals that target monkeypox proteins might lead to more effective and efficient therapy. The F13 protein is essential for the growth and maturation of the monkeypox virus. F13 inhibition might be a viable therapeutic target for monkeypox. The in silico fragment-based drug discovery method for developing antivirals may provide novel therapeutic options. In this study, we generated 800 compounds based on tecovirimat, an FDA-approved drug that is efficacious at nanomolar quantities against monkeypox. These compounds were evaluated to identify the most promising fragments based on binding affinity and pharmacological characteristics. The top hits from the chemical screening were docked into the active site of the F13 protein. Molecular dynamics simulations were performed on the top two probable new candidates from molecular docking. The ligand–enzyme interaction analysis revealed that the C2 ligand had lower binding free energy than the standard ligand tecovirimat. Water bridges, among other interactions, were shown to stabilize the C2 molecule. Conformational transitions and secondary structure changes in F13 protein upon C2 binding show more native three-dimensional folding of the protein. Prediction of pharmacological properties revealed that compound C2 may be promising as a drug candidate for monkeypox fever. However, additional in vitro and in vivo testing is required for validation.

Background: Coronavirus disease 2019 (COVID-19) is a global health threat and caused a universal psychosocial impact on the general population. Therefore, the knowledge, attitude, and perceptions (KAPs) of the general population are critical for the development and effective implementation of standard operating procedures (SOP) to contain the contagion and minimize the losses. Therefore, the current study was conducted to understand and evaluate the KAPs of Pakistani populations toward the COVID-19.Methods: An online cross-sectional study was carried out among participants from 1 May to 30 July 2020 in different areas of Pakistan. The respondents of the study were the general population with age ≥ 18 years. The poll URL was posted on several channels after a call for participation. Other social media platforms such as WeChat, WhatsApp, Facebook, Twitter, Instagram, Messenger, and LinkedIn were engaged to maximize general population engagement. The questionnaire included details about sociodemographic, knowledge about COVID-19, perceptions toward universal safety precautions of COVID-19, and beliefs attitude toward the COVID-19. The obtained data were exported into a Microsoft Excel spreadsheet and SPSS software version 21 for windows. The descriptive statistics values were presented in frequencies and percentages. Binary logistic regression, Chi-square test, and one-way ANOVA were applied to analyze the participants' socio-demographic characteristics and variables related to KAPs. P-value < 0.05 was recorded as significant.Results: A total of 1,000 participants were invited of which 734 participated in this study. The response rate was 73.4% (734/1,000). The gender, marital status, education, and residence showed a significant association with the knowledge score. The majority of the study participants were thinking that COVID-19 may be more dangerous in elderly individuals 94.5% (n = 700), and individuals with chronic diseases or severe complications 96.7% (n = 710) (p = 0.00). More than half of the participants 52.5% (n = 385) showed their concern that either they or their family members might get the infection. More than 98% (n = 703), (P-value = 0.00) of the participants held that COVID-19 would be successfully controlled in Pakistan by following the standard SOPs and government guidelines.Conclusion: This study showed that the general population of Pakistan has good awareness and reasonable attitudes and perceptions toward the full features of the COVID-19. The current study suggests that mass-level effective health education programs are necessary for developing countries to improve and limit the gap between KAP toward COVID-19.

Central nervous system disorders, especially neurodegenerative diseases, are a public health priority and demand a strong scientific response. Various therapy procedures have been used in the past, but their therapeutic value has been insufficient. The blood–brain barrier (BBB) and the blood–cerebrospinal fluid barrier is two of the barriers that protect the central nervous system (CNS), but are the main barriers to medicine delivery into the CNS for treating CNS disorders, such as brain tumors, Parkinson’s disease, Alzheimer’s disease, and Huntington’s disease. Nanotechnology-based medicinal approaches deliver valuable cargos targeting molecular and cellular processes with greater safety, efficacy, and specificity than traditional approaches. CNS diseases include a wide range of brain ailments connected to short- and long-term disability. They affect millions of people worldwide and are anticipated to become more common in the coming years. Nanotechnology-based brain therapy could solve the BBB problem. This review analyzes nanomedicine’s role in medication delivery; immunotherapy, chemotherapy, and gene therapy are combined with nanomedicines to treat CNS disorders. We also evaluated nanotechnology-based approaches for CNS disease amelioration, with the intention of stimulating the immune system by delivering medications across the BBB.

Lung cancer is one of the 10 most common cancers in the world, which seriously affects the normal life and health of patients. According to the investigation report, the 3-year survival rate of patients with lung cancer is less than 20%. Heredity, the environment, and long-term smoking or secondhand smoke greatly promote the development and progress of the disease. The mechanisms of action of the occurrence and development of lung cancer have not been fully clarified. As a new type of gas signal molecule, hydrogen sulfide (H2S) has received great attention for its physiological and pathological roles in mammalian cells. It has been found that H2S is widely involved in the regulation of the respiratory system and digestive system, and plays an important role in the occurrence and development of lung cancer. H2S has the characteristics of dissolving in water and passing through the cell membrane, and is widely expressed in body tissues, which determines the possibility of its participation in the occurrence of lung cancer. Both endogenous and exogenous H2S may be involved in the inhibition of lung cancer cells by regulating mitochondrial energy metabolism, mitochondrial DNA integrity, and phosphoinositide 3-kinase/protein kinase B co-pathway hypoxia-inducible factor-1α (HIF-1α). This article reviews and discusses the molecular mechanism of H2S in the development of lung cancer, and provides novel insights for the prevention and targeted therapy of lung cancer.

Abstract Polypeptide sequences enriched with proline (P), glutamic acid (E), aspartic acid (D) and serine (S)/ threonine (T) (PEST) have been reported to be the most abundant and frequently distributed at the cellular level. There is growing evidence that PEST sequences act as proteolytic recognition signals for degradation of residual proteins which is critical for activation or deactivation of regulatory proteins involved in cellular signaling pathways of cell growth, differentiation, stress responses and physiological death. A PEST containing nuclear protein (PCNP) was demonstrated as a tumor suppressor in a neuroblastoma cancer model and tumor promoter in lung adenocarcinoma cancer model. Its unique properties like ubiquitination by NIRF, co‐localization with NIRF in nucleus and tumor progression attract the attention of researchers. PCNP was reported to be ubiquitinated by ring finger protein NIRF in E3 ligase manner and as modulator of MAPK and PI3K/AKT/mTOR signaling pathways. In this review, we summarize PCNP linked DNA damage response, Post translational modifications, and transportation to address initiation, prognosis, and resistance of tumor cells in terms of cell cycle regulation, transcription and apoptosis. Hence, we demonstrate PCNP as a novel target in cancer diagnosis and treatment.

Objective: The goal of public health in combatting COVID-19 is to increase herd immunity. However, vaccine reluctance makes attaining herd immunity a worldwide challenge. This investigation aimed to identify negative and positive attitudes and intentions about COVID-19 vaccinations. Methods: A cross-sectional online survey was conducted once free COVID-19 vaccines became available in Pakistan in 2021. 4392 Pakistanis aged 18 and older were surveyed from seven administrative units between 1 July and 30 August 2021. Online structured questionnaires were utilized to collect data using a simple sampling procedure. The questionnaires were divided into three major sections: sociodemographic, health factors, and attitudes toward COVID-19. Results: The survey link was shared with approximately 4500 participants. 97.6%(4392) completed the survey once begun. Frequency, percentage and Chi-square tests were used to analyze statistical data. Most of the participants in the research were men (2703 (61.54%)), 3277 (74.61%) were aged 18–29 years, and 1824 (41.53%) were residents of the Khyber Pakhtunkhwa province. (18.69%) Respondents expressed COVID-19 vaccine hesitancy, whereas 36.66% of participants liked getting the Sinopharm and Sinovac vaccines and (35.84%) of participants preferred the Pfizer vaccine. A significant number of participants (38.05%) were concerned about the vaccine’s unexpected side effects Thus, it is essential to realize that many participants were concerned about the vaccine’s unexpected side effects. Conclusions: The overall high level of concern about the unforeseen side effects of COVID-19 vaccines, as well as widespread vaccine hesitancy among Pakistani populations and its predictors, should be taken into account if public health intervention campaigns in Pakistan are changing negative attitudes and improving compliance with regard to COVID-19 vaccines.

Hydrogen sulfide (H2S), as one of the three known gaseous signal transduction molecules in organisms, has attracted a surging amount of attention. H2S is involved in a variety of physiological and pathological processes in the body, such as dilating blood vessels (regulating blood pressure), protecting tissue from ischemia-reperfusion injury, anti-inflammation, carcinogenesis, or inhibition of cancer, as well as acting on the hypothalamus and pancreas to regulate hormonal metabolism. The change of H2S concentration is related to a variety of endocrine disorders, and the change of hormone concentration also affects the synthesis of H2S. Understanding the effect of biosynthesis and the concentration of H2S on the endocrine system is useful to develop drugs for the treatment of hypertension, diabetes, and other diseases.

Alzheimer’s disease (AD) is a devastating disease of the aging population characterized by the progressive and slow brain decay due to the formation of extracellular plaques in the hippocampus. AD cells encompass tangles of twisted strands of aggregated microtubule binding proteins surrounded by plaques. Delivering corresponding drugs in the brain to deal with these clinical pathologies, we face a naturally built strong, protective barrier between circulating blood and brain cells called the blood–brain barrier (BBB). Nanomedicines provide state-of-the-art alternative approaches to overcome the challenges in drug transport across the BBB. The current review presents the advances in the roles of nanomedicines in both the diagnosis and treatment of AD. We intend to provide an overview of how nanotechnology has revolutionized the approaches used to manage AD and highlight the current key bottlenecks and future perspective in this field. Furthermore, the emerging nanomedicines for managing brain diseases like AD could promote the booming growth of research and their clinical availability.

Brain is by far the most complex organ in the body. It is involved in the regulation of cognitive, behavioral, and emotional activities. The organ is also a target for many diseases and disorders ranging from injuries to cancers and neurodegenerative diseases. Brain diseases are the main causes of disability and one of the leading causes of deaths. Several drugs that have shown potential in improving brain structure and functioning in animal models face many challenges including the delivery, specificity, and toxicity. For many years, researchers have been facing challenge of developing drugs that can cross the physical (blood–brain barrier), electrical, and chemical barriers of the brain and target the desired region with few adverse events. In recent years, nanotechnology emerged as an important technique for modifying and manipulating different objects at the molecular level to obtain desired features. The technique has proven to be useful in diagnosis as well as treatments of brain diseases and disorders by facilitating the delivery of drugs and improving their efficacy. As the subject is still hot, and new research findings are emerging, it is clear that nanotechnology could upgrade health care systems by providing easy and highly efficient diagnostic and treatment methods. In this review, we will focus on the application of nanotechnology in the diagnosis and treatment of brain diseases and disorders by illuminating the potential of nanoparticles.

Hydrogen sulfide (H2S), a gaseous signaling molecule, is associated with the development of various malignancies via modulating various cellular signaling cascades. Published research has established the fact that inhibition of endogenous H2S production or exposure of H2S donors is an effective approach against cancer progression. However, the effect of pharmacological inhibition of endogenous H2S-producing enzymes (cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MPST)) on the growth of breast cancer (BC) remains unknown. In the present study, DL-propargylglycine (PAG, inhibitor of CSE), aminooxyacetic acid (AOAA, inhibitor of CBS), and L-aspartic acid (L-Asp, inhibitor of 3-MPST) were used to determine the role of endogenous H2S in the growth of BC by in vitro and in vivo experiments. An in silico study was also performed to confirm the results. Corresponding to each enzyme in separate groups, we treated BC cells (MCF-7 and MDA-MB-231) with 10 mM of PAG, AOAA, and L-Asp for 24 h. Findings reveal that the combined dose (PAG + AOAA + L-Asp) group showed exclusive inhibitory effects on BC cells’ viability, proliferation, migration, and invasion compared to the control group. Further, treated cells exhibited increased apoptosis and a reduced level of phospho (p)-extracellular signal-regulated protein kinases such as p-AKT, p-PI3K, and p-mTOR. Moreover, the combined group exhibited potent inhibitory effects on the growth of BC xenograft tumors in nude mice, without obvious toxicity. The molecular docking results were consistent with the wet lab experiments and enhanced the reliability of the drugs. In conclusion, our results demonstrate that the inhibition of endogenous H2S production can significantly inhibit the growth of human breast cancer cells via the AKT/PI3K/mTOR pathway and suggest that endogenous H2S may act as a promising therapeutic target in human BC cells. Our study also empowers the rationale to design novel H2S-based anti-tumor drugs to cure BC.

Hydrogen sulfide (H2S) is an endogenous biologically active gas produced in mammalian tissues. It plays a very critical role in many pathophysiological processes in the body. It can be endogenously produced through many enzymes analogous to the cysteine family, while the exogenous source may involve inorganic sulfide salts. H2S has recently been well investigated with regard to the onset of various carcinogenic diseases such as lung, breast, ovaries, colon cancer, and neurodegenerative disorders. H2S is considered an oncogenic gas, and a potential therapeutic target for treating and diagnosing cancers, due to its role in mediating the development of tumorigenesis. Here in this review, an in-detail up-to-date explanation of the potential role of H2S in different malignancies has been reported. The study summarizes the synthesis of H2S, its roles, signaling routes, expressions, and H2S release in various malignancies. Considering the critical importance of this active biological molecule, we believe this review in this esteemed journal will highlight the oncogenic role of H2S in the scientific community.

COVID-19 has spread rapidly worldwide since its outbreak and has now become a major public health problem. More and more evidence indicates that SARS-CoV-2 may not only affect the respiratory system but also cause great harm to the central nervous system. Therefore, it is extremely important to explore in-depth the impact of SARS-CoV-2 infection on the nervous system. In this paper, the possible mechanisms of SARS-CoV-2 invading the central nervous system during COVID-19, and the neurological complications caused by SARS-CoV-2 infection were reviewed.

Hydrogen sulfide (H2S) plays a key role in the regulation of physiological processes in mammals. The decline in H2S level has been reported in numerous renal disorders. In animal models of renal disorders, treatment with H2S donors could restore H2S levels and improve renal functions. H2S donors suppress renal dysfunction by regulating autophagy, apoptosis, oxidative stress, and inflammation through multiple signaling pathways, such as TRL4/NLRP3, AMP-activated protein kinase/mammalian target of rapamycin, transforming growth factor-β1/Smad3, extracellular signal-regulated protein kinases 1/2, mitogen-activated protein kinase, and nuclear factor kappa B. In this review, we summarize recent developments in the effects of H2S donors on the treatment of common renal diseases, including acute/chronic kidney disease, renal fibrosis, unilateral ureteral obstruction, glomerulosclerosis, diabetic nephropathy, hyperhomocysteinemia, drug-induced nephrotoxicity, metal-induced nephrotoxicity, and urolithiasis. Novel H2S donors can be designed and applied in the treatment of common renal diseases.

Melanoma is the deadliest skin tumor and is prone to distant metastases. The incidence of melanoma has increased rapidly in the past few decades, and current trends indicate that this growth is continuing. This study was aimed to explore the molecular mechanisms of melanoma pathogenesis and discover underlying pathways and genes associated with melanoma. We used high-throughput expression data to study differential expression profiles of related genes in melanoma. The differentially expressed genes (DEGs) of melanoma in GSE15605, GSE46517, GSE7553, and the Cancer Genome Atlas (TCGA) datasets were analyzed. Differentially expressed genes (DEGs) were identified by paired t-test. Then the DEGs were performed cluster and principal component analyses and protein–protein interaction (PPI) network construction. After that, we analyzed the differential genes through bioinformatics and got hub genes. Finally, the expression of hub genes was confirmed in the TCGA databases and collected patient tissue samples. Total 144 up-regulated DEGs and 16 down-regulated DEGs were identified. A total of 17 gene ontology analysis (GO) terms and 11 pathways were closely related to melanoma. Pathway of pathways in cancer was enriched in 8 DEGs, such as junction plakoglobin (JUP) and epidermal growth factor receptor (EGFR). In the PPI networks, 9 hub genes were obtained, such as loricrin (LOR), filaggrin (FLG), keratin 5 (KRT5), corneodesmosin (CDSN), desmoglein 1 (DSG1), desmoglein 3 (DSG3), keratin 1 (KRT1), involucrin (IVL), and EGFR. The pathway of pathways in cancer and its enriched DEGs may play important roles in the process of melanoma. The hub genes of DEGs may become promising melanoma candidate genes. Five key genes FLG, DSG1, DSG3, IVL, and EGFR were identified in the TCGA database and melanoma tissues. The results suggested that FLG, DSG1, DSG3, IVL, and EGFR might play important roles and potentially be valuable in the prognosis and treatment of melanoma. These hub genes might well have clinical significance as diagnostic markers.

Abstract Background PEST-containing nuclear protein (PCNP), a novel nuclear protein, is involved in cell proliferation and tumorigenesis. However, the precise mechanism of action of PCNP in the process of tumor growth has not yet been fully elucidated. Methods ShRNA knockdown and overexpression of PCNP were performed in human neuroblastoma cells. Tumorigenic and metastatic effects of PCNP were examined by tumor growth, migration, and invasion assays in vitro, as well as xenograft tumor assay in vivo. Results PCNP over-expression decreased the proliferation, migration, and invasion of human neuroblastoma cells and down-regulation of PCNP showed reverse effects. PCNP over-expression increased protein expressions of cleaved caspase-3, cleaved caspase-8, cleaved caspase-9, and cleaved poly adenosine diphosphate-ribose polymerase, as well as ratios of B-cell lymphoma-2 (Bcl-2)-associated X protein/Bcl-2 and Bcl-2-associated death promoter/B-cell lymphoma-extra large in human neuroblastoma cells, however PCNP knockdown exhibited reverse trends. PCNP over-expression increased phosphorylations of extracellular signal-regulated protein kinase 1/2, p38, c-Jun N-terminal kinase, as well as decreased phosphorylations of phosphatidylinositol 3-kinase (PI3K), Akt, and mammalian target of rapamycin (mTOR), nevertheless PCNP knockdown exhibited opposite effects. Furthermore, PCNP over-expression significantly reduced the growth of human neuroblastoma xenograft tumors by down-regulating angiogenesis, whereas PCNP knockdown markedly promoted the growth of human neuroblastoma xenograft tumors through up-regulation of angiogenesis. Conclusions PCNP mediates the proliferation, migration, and invasion of human neuroblastoma cells through mitogen-activated protein kinase and PI3K/AKT/mTOR signaling pathways, implying that PCNP is a therapeutic target for patients with neuroblastoma.

The ongoing outbreak of coronavirus disease COVID-19 is significantly implicated by global heterogeneity in the genome organization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The causative agents of global heterogeneity in the whole genome of SARS-CoV-2 are not well characterized due to the lack of comparative study of a large enough sample size from around the globe to reduce the standard deviation to the acceptable margin of error. To better understand the SARS-CoV-2 genome architecture, we have performed a comprehensive analysis of codon usage bias of sixty (60) strains to get a snapshot of its global heterogeneity. Our study shows a relatively low codon usage bias in the SARS-CoV-2 viral genome globally, with nearly all the over-preferred codons’ A.U. ended. We concluded that the SARS-CoV-2 genome is primarily shaped by mutation pressure; however, marginal selection pressure cannot be overlooked. Within the A/U rich virus genomes of SARS-CoV-2, the standard deviation in G.C. (42.91% ± 5.84%) and the GC3 value (30.14% ± 6.93%) points towards global heterogeneity of the virus. Several SARS-CoV-2 viral strains were originated from different viral lineages at the exact geographic location also supports this fact. Taking all together, these findings suggest that the general root ancestry of the global genomes are different with different genome’s level adaptation to host. This research may provide new insights into the codon patterns, host adaptation, and global heterogeneity of SARS-CoV-2.

Respiratory diseases are leading causes of death and disability around the globe, with a diverse range of health problems. Treatment of respiratory diseases and infections has been verified to be thought-provoking because of the increasing incidence and mortality rate. Hydrogen sulfide (H2S) is one of the recognized gaseous transmitters involved in an extensive range of cellular functions, and physiological and pathological processes in a variety of diseases, including respiratory diseases. Recently, the therapeutic potential of H2S for respiratory diseases has been widely investigated. H2S plays a vital therapeutic role in obstructive respiratory disease, pulmonary fibrosis, emphysema, pancreatic inflammatory/respiratory lung injury, pulmonary inflammation, bronchial asthma and bronchiectasis. Although the therapeutic role of H2S has been extensively studied in various respiratory diseases, a concrete literature review will have an extraordinary impact on future therapeutics. This review provides a comprehensive overview of the effective role of H2S in respiratory diseases. Besides, we also summarized H2S production in the lung and its metabolism processes in respiratory diseases.

Sepsis is the leading cause of death for critically ill patients in recent years. Dendritic cells (DCs) are important antigen-presenting cells and play a key role in immune response by regulating the innate and adaptive immunity. The number of DCs, the differentiation of monocytes into DCs, and the levels of surface molecules associated with the function of DCs are changed in the development of sepsis. There are many mechanisms involved in the alterations of DCs during sepsis, including the induction of apoptosis, reactive oxygen species generation, activation of the Wnt signaling pathway, epigenetic regulation, and variation in Toll-like receptor-dependent signaling. In this review, we present the classifications of DC subsets and mechanisms involved in the alterations of DCs in sepsis, as well as further discuss the therapeutic strategies targeting DCs in sepsis to improve the aberrant immune response and prolong the life during sepsis progression.

The neutrophil is the major phagocyte and the final effector cell of the innate immunity, with a primary role in the clearance of extracellular pathogens. Using the broad array of cytokines, extracellular traps, and effector molecules as the humoral arm, neutrophils play a crucial role in the host defense against pathogen infections. On the other hand, the pathogen has the capacity to overcome neutrophil-mediated host defense to establish infection causing human disease. Pathogens, such as S. aureus, have the potential to thwart neutrophil chemotaxis and phagocytosis and thereby succeed in evading killing by neutrophils. Furthermore, S. aureus surviving within neutrophils promotes neutrophil cytolysis, resulting in the release of host-derived molecules that promote local inflammation. Here, we provide a detailed overview of the mechanisms by which neutrophils kill the extracellular pathogens and how pathogens evade neutrophils degradation. This review will provide insights that might be useful for the development of novel therapies against infections caused by antibiotic resistant pathogens.

Autophagy is an evolutionarily conserved cellular recycling process that maintains cellular homeostasis. Despite extensive research in endocrine contexts, the role of autophagy in ovarian and testicular steroidogenesis remains elusive. The significant role of autophagy in testosterone production suggests potential treatments for conditions like oligospermia and azoospermia. Further, influence of autophagy in folliculogenesis, ovulation, and luteal development emphasizes its importance for improved fertility and reproductive health. Thus, investigating autophagy in gonadal cells is clinically significant. Understanding these processes could transform treatments for endocrine disorders, enhancing reproductive health and longevity. Herein, we provide the functional role of autophagy in testicular and ovarian steroidogenesis to date, highlighting its modulation in testicular steroidogenesis and its impact on hormone synthesis, follicle development, and fertility therapies. [ABSTRACT FROM AUTHOR]