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Methionine aminopeptidases (MetAPs) have emerged as a target for medicinal chemists in the quest for novel therapeutic agents for treating cancer, obesity, and other disorders. Methionine aminopeptidase is a metalloenzyme with two structurally distinct forms in humans, MetAP-1 and MetAP-2. The MetAP2 inhibitor fumagillin, which was used as an amebicide in the 1950s, has been used for the successful treatment of microsporidiosis in humans; however, it is no longer commercially available. Despite significant efforts and investments by many pharmaceutical companies, no new MetAP inhibitors have been approved for the clinic. Several lead compounds have been designed and synthesized by researchers as potential inhibitors of MetAP and evaluated for their potential activity in a wide range of diseases. MetAP inhibitors such as fumagillin, TNP-470, beloranib, and reversible inhibitors and their analogs guide new prospects for MetAP inhibitor development in the ongoing quest for new pharmacological indications. This perspective provides insights into recent advances related to MetAP, as a potential therapeutic target in drug discovery, bioactive small molecule MetAP2 inhibitors, and data on the role of MetAP-2 as a therapeutic target for microsporidiosis.
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Drug delivery systems, which use components at the nanoscale level as diagnostic tools or to release therapeutic drugs to particular target areas in a regulated manner, are a fast-evolving field of science. The active pharmaceutical substance can be released via the drug delivery system to produce the desired therapeutic effect. The poor bioavailability and irregular plasma drug levels of conventional drug delivery systems (tablets, capsules, syrups, etc.) prevent them from achieving sustained delivery. The entire therapy process may be ineffective without a reliable delivery system. To achieve optimal safety and effectiveness, the drug must also be administered at a precision-controlled rate and the targeted spot. The issues with traditional drug delivery are overcome by the development of stimuli-responsive controlled drug release. Over the past decades, regulated drug delivery has evolved considerably, progressing from large- and nanoscale to smart-controlled drug delivery for several diseases. The current review provides an updated overview of recent developments in the field of stimuli-responsive boron-based materials in drug delivery for various diseases. Boron-containing compounds such as boron nitride, boronic acid, and boron dipyrromethene have been developed as a moving field of research in drug delivery. Due to their ability to achieve precise control over drug release through the response to particular stimuli (pH, light, glutathione, glucose or temperature), stimuli-responsive nanoscale drug delivery systems are attracting a lot of attention. The potential of developing their capabilities to a wide range of nanoscale systems, such as nanoparticles, nanosheets/nanospheres, nanotubes, nanocarriers, microneedles, nanocapsules, hydrogel, nanoassembly, etc., is also addressed and examined. This review also provides overall design principles to include stimuli-responsive boron nanomaterial-based drug delivery systems, which might inspire new concepts and applications.
Asunto(s)
Nanocápsulas , Nanopartículas , Nanosferas , Polímeros de Estímulo Receptivo , Boro , Sistemas de Liberación de Medicamentos , Nanopartículas/química , Portadores de Fármacos/química , Liberación de FármacosRESUMEN
The forensic literature has described unusual wounds of entry into fatal stab wounds that are rarely found in autopsies. Stab wounds are considered fatal injuries when they occur in vital organs. Many authors have suggested that the description of the wound track helps recreate the crime scene. Still, many say that the recreation of a crime scene is a static event, whereas the actual event is dynamic. We received the dead body of a 25-year-old male for postmortem examination. During autopsy, we found a wedge-shaped stab wound in the epigastric region. Interestingly, when we dissected the skin and subcutaneous tissue without disturbing the wound, we observed two separate wedge-shaped wounds over the rectus sheath. A knife can produce an atypical appearance after plunging into the body. With a single external primary stab wound, two different wound tracks can be made internally. Thus, examining only the wound track made it impossible to comment on the circumstances of violence.
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Introduction The Protection of Children from Sexual Offences (POCSO) Act in India prohibits sexual engagement among individuals under 18 years old. However, societal variables also affect many teenagers' consensual sexual activities. Little research has been conducted on the legal ramifications for consenting to sexual action under the POCSO Act. This study examined consensual sexual assault cases under the POCSO Act and their possible outcome. Methodology Five years of medicolegal records from a tertiary hospital were analyzed for sexual assault victims aged <18 years. Descriptive statistics were used to analyze victim demographics, literacy, sexual acts, reporting patterns, and accused-victim relationships. Result A total of 410 instances of sexual assault were recorded, and 29% involved victims between the ages of 16 and 18. Most victims (73.9%) in this age range were literate, and 85.7% provided consent for sexual relations. Parents or guardians reported all cases, and most of the accused were victims' friends. Discussion The POCSO Act offers legal safeguards for sexual abuse and exploitation. However, their use in adolescent sexual consent has raised concerns. The Law Commission of India's refusal to reassess the POCSO Act's age barrier for sexual consent emphasizes the need for a child-centric approach to negotiating complex teenage relationships. Conclusion Balancing legal obligations and developmental needs is essential to addressing consensual sexual acts under the POCSO Act. While sensitively implementing the law, stakeholders must focus on their children's best interests and healthy development. Child-friendly environments and support systems empower victims and reduce trauma in teenage relationships.
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In cases of traumatic deaths, accurate assessment of injuries is essential for both legal and medical purposes. This case report compares the findings of post-mortem computed tomography with conventional autopsy methods in assessing abdominal stab wounds. A 34-year-old woman with multiple stab wounds in the abdomen underwent post-mortem examination, including computed tomography imaging. Computed tomography revealed specific breaches in the skin's continuity and internal injuries, including perforation of the stomach. A conventional autopsy confirmed the presence of multiple stab wounds and associated injuries to internal structures. However, additional injuries to major blood vessels, such as the abdominal aorta and inferior vena cava, were only detected during manual exploration of the peritoneal cavity. This case highlights the complementary roles of post-mortem computed tomography and conventional autopsy in evaluating traumatic injuries. While computed tomography imaging offers non-invasive visualisation of injuries, manual examination remains essential for identifying certain injuries, particularly those affecting major blood vessels. The integration of computed tomography imaging with traditional autopsy methods enhances the accuracy and reliability of forensic assessments in cases of traumatic deaths, particularly in complex cases involving multiple injuries. Understanding the strengths and limitations of these techniques is crucial for improving forensic investigations and ultimately enhancing medico-legal outcomes.