Medicina molecular y genética

El rechazo mediado por células T (TCMR) se volvió controlable y la supervivencia a largo plazo del injerto renal llegó a obtenerse gracias al reciente progreso e innovación de los inmunosupresores. Mientras que la profilaxis y el control del rechazo mediado por anticuerpos (ABMR) causado por el anticuerpo anti-HLA específico del donante (DSA) aún son insuficientes y afectan la supervivencia a largo plazo del injerto renal. El DSA se clasificó aproximadamente de la siguiente manera: DSA preexistente existente en los pacientes antes del trasplante renal (RTx) y DSA de novo producida en los pacientes después del RTx. Hay muchos informes sobre el efecto que el DSA preexistente da a un inyector renal, y el tratamiento para ABMR con DSA preexistente está establecido hasta cierto punto. A diferencia del DSA preexistente, no se puede decir que los DSA de novo se consideran suficientes en la actualidad. En este estudio, examinamos el impacto que el DSA de novo dio a un inyector renal en 40 pacientes con RTx bajo tratamiento en nuestro hospital. Aunque no hubo diferencias significativas en cuanto a la función del injerto renal en el grupo DSA positivo y negativo, la supervivencia del injerto renal mostró una tendencia a ser mejor en un grupo DSA negativo que en un grupo positivo (85% frente a 55%, P = 0,0553). Realizamos un seguimiento del DSA de novo de forma positiva y deberíamos contribuir a la mejora de los pronósticos del inyector renal en el futuro.

Antecedentes: La combinación aceptada de quimioterapia y cirugía es actualmenteda para el tratamiento de pacientes con metástasis hepáticas colorrectales técnicamente resecables. Sin embargo, es difícil determinar cuál de estas modalidades debe ser el tratamiento de elección. En este estudio, evaluamos la utilidad de la diferencia en el tamaño del tumor evaluado en imágenes preterapéuticas para la selección de la quimioterapia en estos pacientes.

Métodos: Presentamos una revisión retrospectiva de 80 metástasis hepáticas colorrectales consecutivas sin tumores extrahepáticos. Se evaluaron y compararon la supervivencia libre de caída (SLR), la supervivencia libre de progresión (SLP) y la supervivencia global (SG) entre pacientes sometidos a cirugía (n = 66) y quimioterapia (n = 14) según las características clínicas. En particular, abordamos los estudios de imágenes preterapéuticos, incluida la distribución y el número de tumores hepáticos metastásicos. Además, se calculó la relación del tamaño del tumor (tumor más grande con el más pequeño); se compararon dos grupos clasificados como R < 5 (proporción < 5) y R ≥ 5 (proporción ≥ 5).

Resultados: Se realizó un análisis univariado en el grupo de cirugía; se encontraron diferencias significativas en RFS con respecto al momento de aparición, el número de tumores y la relación de los diámetros tumorales. El análisis multivariado mostró que la relación del tamaño del tumor, R ≥ 5, fue el único factor de riesgo pronóstico independiente con respecto tanto a RFS como a SG. Luego comparamos el resultado de los pacientes con factores de riesgo pronóstico entre cirugía y quimioterapia. La cirugía logró una SG significativamente mejor que la quimioterapia, con la excepción del grupo R ≥ 5. No se observaron diferencias en la SG, además de RFS y PFS, en los grupos R ≥ 5 independientemente del tratamiento.

Conclusión: Los pacientes con cáncer colorrectal con metástasis hepáticas resecables con R ≥ 5 no mostraron diferencias significativas en los resultados obtenidos con cirugía o quimioterapia. La quimioterapia podría utilizarse como alternativa a la cirugía de revascularización para abordar problemas oncológicos como la presencia de metástasis latentes o un mal resultado del tratamiento en estos pacientes.

El CD40, miembro de la superfamilia del factor de necrosis tumoral (TNF), se expresa ampliamente en una variedad de células. Hay estudios que sugieren que la expresión del CD40 está relacionada con varias neoplasias malignas, mientras que sus cualidades terapéuticas innatas aún están por confirmar. El cáncer de colon es uno de los cánceres más comunes, mientras que poco se puede hacer por los pacientes con cáncer de colon avanzado, incluso en el momento actual. El CD40 está presente en el cáncer de colon y es un posible objetivo de inmunoterapia terapéutica para mejorar las tasas de supervivencia general de los pacientes con enfermedad avanzada.

Presentamos un caso de músculo palmar largo Accesorio en el que el vientre muscular se encontraba distal al tendón y no causaba compresión del nervio mediano. Este fue un hallazgo incidental durante la investigación de un dolor de muñeca.

Esophageal malignancies are usually encountered in patients over 50 years old and are associated with significant morbidity and mortality. Efforts to improve patient outcomes are slowly shifted towards unravelling the molecular basis of esophageal cancer as this approach could lead to designing individualized treatment protocols and implementing precision medicine paradigms. Our aim was to present recent advances in esophageal adenocarcinoma genomics, epigenetics and molecular biology with regards to their role on disease pathophysiology, patient outcomes and applications to clinical care. Disease progression is correlated with missense mutations and in-frame deletions of EGFR, as well as with upregulation of a variety of genes (CXCL1 CXCL3, GATA6 and DMBT1), microsatellite instability and telomerase overexpression. On the other hand, p53 loss of heterozygosity as well as HER2 and c-MYC amplifications tend to develop in later stages of the disease and are associated with poor prognosis. Downregulation of CDKN2A, e-cadherin, SMAD4, RUNX3 and aneuploidy/tetraploidy are also correlated with unfavorable outcomes. Lastly, p53 immunohistochemistry and methylation panels are already being applied in clinical practice.

Parkinson’s is second most common neurological disorder in the world having both sporadic and familial cases. Present Parkinson’s disease genetics taxonomy specifies 18 chromosomal regions that are also called chromosomal locus which are termed PARK. Gene therapy i.e., Use of genes as medicine, is effective and newly discovered treatment of many Central nervous system disorders including Parkinson’s disease. Direct injection was also performed but it does not give suitable results. So, scientist feel need of using different vectors for efficient delivery of genes in Central nervous system. Hence gene therapy of Parkinson’s disease involves use of both viral and non-viral vectors but viral vectors shows efficient results. Frequently used vectors for therapy of Parkinson’s disease are Lentivirus and adeno associated virus. Using these vectors many successful experiments are performed on different animals. Parkin, Glial cell-derived neurotrophic factor (GDNF) and alpha synuclein are some of the successful products for therapy of Parkinson’s disease.

Among the tumors of the kidney, the clear cell papillary renal cell carcinoma (CCPRCC) is a recently described entity. This tumor is well circumscribed, with a fibrous capsule, showing mostly a prominent cystic component and a diameter less than 4 cm. Necrosis is not a feature. Tumor cells are clear with low grade nuclei with a predominantly tubule-papillary architecture and immunohistochemical staining strongly positive for CK7, and for CA IX and negative for RACEMASE, features which differentiate this tumor from clear cell renal cell carcinoma (CCRCC) and papillary renal cell carcinoma (papillary RCC). In these latter tumors, it has been reported, unlike the other two, no loss or gain of chromosomes 7 and Y, no chromosome 3p deletion, and no KRAS mutation. In this report, a huge clear cell papillary renal cell carcinoma case, 9 cm diameter, in a 42-year-old male is described. Pathologic diagnosis of the tumor was confirmed by immunohistochemical analysis including CD10, CA IX, CK7, RACEMASE, and 34 beta E12 stainings. Molecular detection of KRAS, BRAF, NRAS, PIK3CA, ALK, ERBB2, DDR2, MAP2K1, RET, and EGFR gene mutational analysis has also been performed. Molecular findings are in accordance with the speculation that the CCRCC is an indolent tumor which may be defined as low malignant potential. In fact, in the molecular analysis, none out of all genes evaluated showed mutation.

Alzheimer’s disease is an autosomal dominant neurodegenerative disease manifested by core symptoms of cognitive decline and memory impairment. This progressive disorder with an insidious onset typically appears in older individuals, but may also affect young people, even in their 30s. It is well established that mutations in amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2) cause Alzheimer’s disease. PSEN1 mutation is more common in Familial Alzheimer’s disease compared with PSEN2 and APP. Two patients fulfilling the NINCDS-ADRDA criteria for probable and definite Alzheimer’s disease were assessed. Two PSEN1 mutations (p.L392P and p.M233L) were identified from 2 probable early-onset familial Alzheimer’s disease (EOFAD) families, respectively. The p.L392P and p.M233L mutations were associated with prominent early onset, rapidly progressive dementia, and neurologic symptoms. Both p.L392P and p.M233L were predicted or confirmed to be pathogenic, and the p.L392P mutation in PSEN1 is the first report in China.

The conventional medicine has failed to treat such disorders which arise by cell dysfunction or death, thus necessitating reimbursement of body’s natural regenerative power. Among all the cell types known to date, stem cells provide the best source for augmenting these dysfunctional or dead tissues owing to their intrinsic capability to differentiate into any cell type. Combined with the knowledge of genomics and DNA sequencing, translational stem cell research became not only a reality but it bought a renaissance in regenerative medicine. Like any pioneering technology, this stem cell technology also faced legal, ethical and socio-religious concerns owing to its diverse applications. Human greed and opportunism also crept in which created unnecessary chaos and hype in the sublime and honoured hope which this branch of science had bought into current medicine.

Nano Enabled Drug Delivery (NEDD) is widely researched and developed to improve the administration and efficacy of pharmaceutical compounds and molecules. To understand the research situation of NEDD from macro perspectives, we used the patent data to analyze from three aspects and got some interesting results: NEDD was developing steadily, but “safety problems” were becoming big challenges in recent years. NEDD was a highly interdisciplinary emerging field, whose more attractive subsystems were “vector” and “cargo”. One superpower, US, and several strong countries formed the global research pattern. Such “tech mining” offers a systematic perspective on the emerging science or technology under study that is not readily achievable within the individual knowledge of particular researchers.

Based on the hypothesis that consistent high carbohydrate diet (HCD) can induce insulin resistance (IR), the present study therefore investigated the induction of IR by feeding HCD. Novelty of the study is to evaluate the effects on pancreas, liver, and kidney tissues histology after eight weeks administration of melatonin and chromium picolinate (CrPic) either in single or in combination (melatonin+CrPic) to HCD rats’ respectively. The male Wistar rats were divided into five groups of six rats each. Group I served as control to which normal diet was given, while unlimited HCD was given to group II Group III, IV, and V were also given melatonin, CrPic, and melatonin+CrPic along with HCD in that order. Histopathologic findings of HCD rat pancreatic tissue suggested that the diet altered the normal structure of islets with concomitant lesser cytoplasmic granularity in acinar cells. HCD rat liver showed enlarged hepatocytes with narrowing of sinusoidal spaces. Results revealed after administration of melatonin and CrPic either in single or in combination (melatonin+CrPic) to HCD rats for 8 weeks normalized pancreas and liver alterations when compared with HCD rat pancreas and liver tissues respectively. The present study clearly shows that HCD-fed male Wistar rats that are destined to attain IR and T2DM through diet can be prevented by giving melatonin and CrPic administration in alone or in combination. Promoting this research area through in vitro and in vivo studies will help us to understand melatonin+CrPic mechanistic insights that may ultimately assist clinicians in controlling hyperglycaemia by supplementing as an add-on therapy.

The tribal populations are is recognised as socially and economically vulnerable. Their lifestyles and food habits are different from that of their rural neighbours. They depend on minor forest produce and manual labour for livelihood. They may not have adequate income. Their food consumption pattern is dependent on the vagaries of nature and varies from extreme deprivation (in the lean seasons) to high intakes (in the post-harvest period). About 21% of them are scheduled castes and 24% are tribes. Purulia suffers from very poor conditions in terms of hygiene, poverty, and lack of safe drinking water, resulting in major health problems such as diarrhoea, malaria, filarial, TB, anaemia, and others. Poor child birth and nutrition standards lead to high IMR and MMR. Open defecation, lack of sanitary latrines, poor educational standards for girl children, and poor awareness of HIV/AIDS also compound Purulia's health and development problems. Tribal people are known to have sexual practices that vary from those of mainstream cultures. Less or nothing is known about the prevalence of HIV and AIDS among tribal people in India, except perhaps in some of the tribal states of the North-East of India as these have high prevalence of drug use. HIV and AIDS has become the fourth largest killer worldwide, and in Asian counterpart which is scattering at an alarming rate. In developing countries, it was estimated that at least half of the non-pregnant and two thirds of the pregnant Women are anaemic. Maternal malnutrition which was quite common among the tribal women was also a serious health problem especially for those having numerous pregnancies too closely spaced and reflected the complex socio-economic factors that affected their overall condition.

Congenital hypothyroidism, defined as the functional deficiency of thyroid hormones present at birth, occurs in approximately 1: 2,000 to 4,000 newborns. Thyroid hormones play an essential role in the maturation of the central nervous system. Congenital hypothyroidism results in severe neurodevelopmental impairment if untreated and, therefore constitutes the most common preventable endocrine cause of irreversible mental retardation. As clinical diagnosis of hypothyroidism in the newborn period is almost always overlooked, newborn screening programs seeking to identify elevated thyrotropin levels at birth are available to detect primary congenital hypothyroidism mainly. Significantly, early onset on levothyroxine replacement therapy virtually abolishes severe intellectual development.

Congenital hypothyroidism is caused by genetic defects occurring at three different levels, including the hypothalamic-pituitary axis, the thyroid gland, and the peripheral tissues. Up to date, 30 monogenic forms of congenital hypothyroidism have been reported in individuals with thyroid dysgenesis, thyroid dyshormonogenesis, central and peripheral hypothyroidism, highlighting the genetic heterogeneity of the disease.

This mini-review summarizes the latest advances in the genetic basis of monogenic forms of congenital hypothyroidism and novel strategies to uncover the molecular etiology of the disease. Moreover, the article provides the current knowledge and future perspectives on the clinical relevance of the molecular diagnosis in patients with congenital hypothyroidism.